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THE THYROID 

AND 

PARATHYROID GLANDS 



RICHARDSON 



The Thyroid 



AND 



Parathyroid Glands 



BY 

HUBERT RICHARDSON, M.D. 

LATE PATHOLOGIST TO MOUNT HOPE RETREAT; PATHOLOGIST TO MARYLAND ASYLUM AND 

TRAINING SCHOOL FOR FEEBLE-MINDED CHILDREN; DEMONSTRATOR OP 

PHYSIOLOGIC CHEMISTRY, UNIVERSITY OP MARYLAND 



WITH SEVENTY-SEVEX HALF-TONE ILLUSTRATIONS MADE 
FROM SPECIAL DRAWINGS BY F. P, WIGIITMAN 



.. PHILAbELPKIA ^ r^. / 

P. B'LAKlSTOfrs"sbN-8r CO. 

IOI2 WALNUT STREET 
1905 



Copyright 1905, By P. Blakiston's Son & Co. 



PdEM Of 

TMt Ntw Era PmNTiNQ com^anv 

LANCMTU. P*. 






PREFACE. 



The work that has been done on the thyroid and para- 
thyroid glands within the past ten or fifteen years has 
contributed to medical literature one of its most bril- 
liant chapters. The careful elucidation of their physi- 
ological functions, the discovery of the active principle 
of the thyroid and its therapeutic application, has filled 
us with wonder and surprise. But a few years ago the 
most advanced text-books gave them but a passmg ref- 
erence and dismissed the whole subject with the vague 
suggestion that the gland was constructed and placed in 
its position by the Divine Architect of the human body 
as an ornament to the neck, like a bit of molding in a 
house or a Doric finish to a column. Later it was sup- 
posed to have some relation to the voice, or to regulate 
in some compensatory manner the intracranial blood sup- 
ply, but nothing was known of its true function and im- 
portance. 

Since Brown-Sequard and Bernard emphasized the 
theory of an internal secretion, which brought upon the 
former an avalanche of ridicule, and Sir William Gull 
and Murray followed in rapid succession with their start- 
ling revelations concerning the function of this ** terra 
incognita," it has been my great pleasure to follow, with 
enthusiastic interest, the contributions throwing new light 
on this subject, and apply to practical therapeutics the 
facts made clear by these investigations and observations. 

Following in rapid succession after the discovery of the 
function of the thyroid gland came the announcement that 
certain conditions of a grave and persistent character 
were due to the congenital or acquired absence or abridg- 



28820 



VI PREFACE. 

ment of the gland, and that these were relieved by en- 
grafting a gland from a healthy animal into the peri- 
toneum or other parts of the body, or by injecting hypo- 
dermically a glycerin solution of the gland of the sheep, 
and finally that the same purpose could be accomplished 
by the use of the fresh gland per orem. Then came the 
discovery that the gland could be desiccated and used 
as any other drug with equal eflScacy and with greater 
accuracy. 

Further research soon developed the fact that still other 
conditions, chiefly associated with arrested, retarded or 
perverted development, either of a physical or psychical 
character, but generally both constituting what the French 
have called **type Loraine" have been found to be asso- 
ciated with an arrested development of the organ and 
could be relieved by the administration of the dried gland. 

It has been also demonstrated that certain functions, 
chiefly menstruation and gestation, demand an extra ex- 
penditure of thyroid secretion, which, if not supplied, 
leads to distinct symptoms, which are also relieved by 
the administration of the dried gland. 

Not resting here, earnest investigations have shown 
that it is a most potent oxidizer, with all the far-reaching 
effects of such an agent on the animal economy, and that 
it is a blood pressure reducer of seemingly a more exact 
and reliable character than any remedy heretofore found 
in our materia medica. 

Developments are also being rapidly made concerning 
other ductless glands and those having an internal secre- 
tion that affect the normal relation and balance of the 
human economy. The suprarenal gland has become a 
standard therapeutic agent to a less degree, but suflScient 
to give promise of further development in the future. 

That the therapeutic applications of the pharmaceutical 
preparations of these glands are not more extensively 



PREFACE. Vll 

availed of in medical practice is due, no doubt, to the 
fact that these useful developments have not yet been 
crystallized into the text-books, and, being scattered 
through the medical literature of many languages, have 
not been made available to the rank and file of the profes- 
sion. Appreciating the therapeutic possibilities of the 
animal glands, I often have occasion to regret that the 
brilliant results of the work that is being done along these 
lines has never, as far as I know, been collected into one 
comprehensive volume, so that it can be availed of with- 
out an amount of research with the necessary access to 
libraries that are not within reach of the average physi- 
cian. It was on this account that I urged Dr. Richardson 
to give to the profession a compilation of the whole sub- 
ject, adding his personal observations and the scientific 
researches he has made in following up the practical ap- 
plication, with analyses of the human gland under various 
conditions of mental and physical impairment, and also 
by his urinalyses and blood examinations, as well as the 
blood-pressure tests of those to whom it was being ad- 
ministered, especially among the insane and degenerates, 
while pathologist at Mount Hope Retreat. 

His capacity for research, his familiarity with the sev- 
eral languages in which the best literature on the subject 
has been written, and his general versatility render him, 
in my opinion, most capable of doing this work, and I 
feel assured that his book will supply a need as much felt 
by the other members of the profession as by myself. 
I am convinced that it will be well and thoroughly done, 
and I am sure I can vouchsafe it a kind and generous 
reception. 

CHAS. G. HILL, A.M., M.D., 

Professor of Nervous and Afcntal Diseases, Baltimore 
Medical College; Physician-in-Chief to Mount Hope 
Retreat. 



CONTENTS. 

Chapter I. 
Historical 1 

Ch-vpter II. 
Embryology— Anatomy— Histology— The Parathyroids 8 

Chapter III. 
Physiology 20 

Chapter IV. 
Chemistry of the Thyroid Gland •. 56 

Chapter V. 
Goitre 73 

Chapter VI. 
Surgery of the Thyroid Gland 100 

Chapter VII. 
The Thyroid in Infectious Diseases 121 

Chapter VIII. 
Acute Thyroiditis 129 

Chapter IX. 
Syphilis of the Thyroid 139 

Chapter X. 
Cretinism 144 

Chapter XI. 
Myxedematous Infantilism 164 

Chapter XII. 
Myxedema 188 

Chapter XIII. 
Basedow's Disease 199 

Chapter XIV. 

Thyroid Feeding in General Therapeutics 233 

Bibliography 255 

Index 259 

ix 



LIST OF ILLUSTRATIONS. 



1. The position of the thyroid after removal of the muscles 

(v. Eiselsberg) 9 

2. Absence of isthmus (Marshall) 10 

3. Isthmus with large pyramid (Marshall) 10 

4. Double pyramid (Marshall) 11 

5. Absence of isthmus with pyramid on left side (Mar- 

shall) 11 

6. The thyroid arteries (v. Eiselsberg) 13 

7. Normal thyroid gland 14 

8. The position of the parathyroid glands (Zuckerkandl) 16 

9. Normal parathyroid gland 18 

10. Monkey in tetanic attack after extirpation of thyroid 

(v. Eiselsberg) 35 

11. A four months old kid whose thyroid was removed at 

21 days old (v. Eiselsberg) 39 

12. Control animal from the same birth (v. Eiselsberg) ... 39 

13. Lamb, 6 months old, the thyroid being removed on the 

tenth day (v. Eiselsberg) 41 

14. Control animal (v. Eiselsberg) 43 

15. Aorta of thyroidectomized sheep showing atheroma (v. 

Eiselsberg) 44 

16. Circular stricture of the trachea from goitre (Demme) 80 

17. Bayonet-shaped trachea from bilateral goitre (Demme) 81 

18. Showing the enlarged veins in goitre (Wolfler) 82 

19. Bending and narrowing of the trachea by goitre 

(Demme) 83 

20. Goitre of accessory thyroids ( Adjutolo) 84 

21. Retrosternal goitre in a deep-seated thyroid lobe f Wuhr- 

man) 85 

22. Intrathoracic goitre (Dittrich) 85 

23. Follicular goitre (v. Eiselsberg) 86 

24. Goitre marked by diffuse follicular hypertrophy (v. 

Mikulicz) 87 

25. Colloid goitre (v. Bruns) 88 

26. Follicular goitre with ectasia of the veins of the skin 

(v. Eiselsberg) 89 

xi 



Xll LIST OP ILLUSTBATIONS. 

27. Cystic goitre (v. Billroth) 90 

28. Cystic goitre (v. Bnins) 91 

29. Struma vasculosa 110 

30. Adenoma of thyroid 110 

31. Cachexia strumipriva in a girl 26 years old (v. Bnins) 116 

32. Congestion of the thyroid 122 

33. Tuberculosis of thyroid 135 

34. Columnar celled carcinoma of thyroid gland 141 

35. Adeno-carcinoma of thyroid gland 141 

36. Cretin with goitre (v. Bruns) 145 

37. Cretin with goitre (v. Mikulicz) 146 

38. Cretin, 22 years old (v. Wagner) 147 

39. Cretin (v. Wagner) 148 

40. Acute thyroiditis 150 

41. Suppurative struma of thyroid gland 150 

42. Atrophic gland from a case of myxedema 152 

43. Myxedematous gland 153 

44, 45. A case of sporadic cretinism before and after thy- 
roid feeding (v. Bruns) 156 

46, 47. A case of sporadic cretinism, aged 6 years, before 

and after 6 months' thyroid feeding 158 

48. Cretin, aged 12 years (Dr. Rogers) 160 

49. Skull of cretin calf 162 

50. Infantilism, aged 17 years (Hertoghe), before treatment 166 

51. Infantilism, aged 17 years (Hertoghe), after 6 months' 

treatment 166 

52. Infantilism, aged 17 years (Hertoghe), after 1 year's 

treatment 166 

53. Infantilism, aged 17 years (Hertoghe), after 2 years' 

treatment 166 

54. Skiagram of the hand of a type Loraine 17 years old. . 168 

55. Skiagram of the hand of normal child 6 years old 169 

56. Skiagram of the hand of a case of myxedema 19 years 

old 169 

57. Skiagram of the hand of a type Loraine, 16 years old. . 170 

58. Skiagram of a normal hand 20 years old 171 

59. A case of infantilism, 19 years of age (author's case), 

before treatment, height 4 ft. 6^ in., weight 76 lbs. 172 

60. A case of infantilism, 19 years of age (author's case), 

after treatment, height 4 ft. 11 in., weight 92 lbs. 172 

61. Infantilism simulating type Loraine, aged 21 years 

(Hertoghe), before treatment 174 



LIST OP ILLUSTRATIONS. xiii 

62. Infantilism simulating type Loraine, aged 21 years 

(Hertoghe), after 4 months* treatment 174 

63. Infantilism simulating type Loraine, aged 21 years 

(Hertoghe), after 7 months' treatment 174 

64. Normal boy 17 years 177 

65. Type Loraine, 27 years 177 

66. Myxedematous infantilism, 18 years 177 

67. 68. Achondroplasia (Comby) 181 

69. Myxedema 184 

70. Incomplete myxedema (Hertoghe), before treatment.. 192 

71. Incomplete myxedema (Hertoghe), after 6 months' 

treatment 192 

72. Incomplete myxedema (Hertoghe), before treatment.. 193 

73. Incomplete myxedema (Hertoghe), after treatment... 193 

74. Basedow's disease 200 

75. Thyroid gland in Basedow's disease ' 22? 

76. 77. Masked Basedow's disease with slight exophthalmos 227 



THE THYROID AND 
PARATHYROID GLAISTDS. 



CHAPTER I. 
HISTORICAL. 



The use of animal organs in medicine dates from very 
early times. Plinius states that the Greeks and Romans 
used the testicles of asses and even the semen for impo- 
tence ; in Albania these organs are used for the same pur- 
pose today, and also for amenorrhea. Paracelsus, in the 
sixteenth century, recommended the spleen for the latter 
condition. Among barbarous and semi-civilized peoples, 
as well as among the peasantry in all countries, these cus- 
toms exist. The Chinese physician prescribes dried mouse 
and lizard ; the native African uses the liver of snakes both 
internally and externally as an antidote for snake bite; 
the warrior eats the heart of the lion to give him courage. 
In Southern France snails are used for indigestion as well 
as a luxury; in Cornwall and Devonshire earthworms 
are given for the same purpose. In the materia medica, 
pepsin, pancreatin, ingluvin, codliver oil and ox gall are 
official, all of which are animal extracts connected with 
the digestive functions, so that the use of other organs or 
their extracts is but a short step in organotherapy. 

In recent times Brown-Sequard reawakened interest in 
the subject by his scientific experiments of removing the 
glands from animals and observing the result. 

He argued that every gland of the body, whether it 
1 1 



2 THE THYBOID AND PARATHYKOID GLANDS. 

possessed an excretory duct or not, produced a secretion 
which was necessary for the well being of the organism, 
and that it should be possible when an organ ceased to 
functionate to substitute the secretion of healthy glands 
either by transplantation, hypodermic injection of the 
extract or feeding by the mouth. His first attempt was 
the use of orchitic extract, christened '^Brown-Sequard 
Elixir," for sterility or impaired virility. The remedy 
was a failure and brought much undeserved ridicule upon 
its advocate, but his reputation as a scientist caused others 
to investigate the subject, resulting in the discovery of 
the use of the thyroid gland in myxedema, which is one 
of the greatest triumphs of medicine in the nineteenth 
century. Brown-Sequard's statements were investigated 
by the Biological Society of Paris, and they reported that 
by the injection of semen and orchitic extract there was 
produced a marked increase in both mental and physical 
force. These experiments and the report excited the pub- 
lic into a belief that the elixir of life had been discovered^ 
and that old age could be rejuvenated, with the natural 
consequence that pharmaceutical preparations appeared 
on the market with the most extraordinary advertise- 
ments. Notwithstanding all this, the foundation was laid, 
and many workers have been steadily perfecting organ- 
otherapy, so that two glands at least, the thyroid and the 
adrenals, have taken a definite place in medicine. 

There can be no doubt that the testicles and ovaries 
have a further function than to secrete the substances 
necessary for procreation. The effect of castration on the 
mental and physical condition is well known. In those 
castrated before puberty, as the ^'castratos" of Italy, 
there is an arrest of development, both mental and, to a 
certain extent, physical ; the voice remains childish, while 
their physical appearance and mannerisms are those of an 
overgrown child, with a tendency to effeminacy. Those 



HISTOBICAL. 3 

castrated after puberty are heavy, sullen, suspicious-look- 
ing men, without energy or ambition, while as a rule their 
mentality is below the average. 

Whatever may be the active agent in the testicles, the 
absence of which produces these results, it has so far been 
impossible to supply its place by the use of Brown- 
Sequard's extract. The experiments of Fiirbringer and 
Pulawski in Germany and Fere, Baudin, Bouffee in 
France gave only negative results. 

The Bussian chemist, Poehl, after much careful an- 
alysis, extracted spermin from the testicle. He found 
that the ovaries, salivary glands, thyroid, liver, spleen, 
and probably the brain substance, also contained spermin 
in small quantities, and argued that this substance circu- 
lated in the organism and was of physiological importance. 
A vast amount of experimental work was carried out by 
Tarchanow and others. They found that the resistance 
of the nerve centers was increased, so that the convulsions 
of strychnin and tetanus were controlled, and also that 
young dogs injected with spermin developed more quickly 
and better than the control animals. They summarized 
their results by saying that spermin was an energetic 
stimulant of the nervous system and probably also of 
other organs, and that it increased the muscle force by 
raising the blood pressure. 

Ovarian extract has several advocates. Muret gives 
four reasons for its use: (1) without ovaries there is no 
uterine development or menstruation; (2) ablation of 
ovaries in young children causes them to grow up without 
feminine attributes; (3) after puberty loss of ovaries 
entails cessation of menstruation and atrophy of genital 
organs; (4) osteomalacia is sometimes cured by oopho- 
rectomy. The extract has not come into general use, but 
there seems to be considerable evidence of its value dur- 
ing the menopause, in some cases of chlorosis and in 



4 THE THYBOID AND PABATHYROID GLANDS. 

dysmenorrhea. At Mount Hope Ketreat it was tried in 
some nervous and mental eases said to be the result of 
laparotomy and in a few other cases where it was thought 
genital trouble existed without any apparent beneficial 
results. In a paper read before the American Medico- 
Psychological Society in 1898, Dr. K. S. Dewey stated, 
that operations on the genitourinary organs stood first 
on the list of surgical operations producing mental dis- 
turbance. Considering that the most important periods 
of life are coincident with changes in the genital organs, 
and that the effect of even such a small defect as lacera- 
tion of the cervix will produce very considerable nervous 
symptoms, it does not appear unreasonable to suppose 
that the normal functionation of the organs of generation 
is necessary for the health of the organism, and that the 
ovaries and testicles being secretory in their nature should 
supply to the system something necessary for its well 
being. 

The thymus gland has been used in many different dis- 
eases without any very definite results. It was first given 
to a patient suffering from Basedow 's disease in mistake 
for thyroid by Dr. Owens. As it produced an apparent 
beneficial effect, it was tried in other cases with varying 
results. Svehla attempted to determine its physiological 
effect, coming to the following conclusions : Injection into 
the femoral vein produced a fall in blood pressure, due to 
weakening or paralysis of the vasoconstrictors, with in- 
crease in the pulse rate, due to direct influence on the 
heart; large doses produced an excitement, dyspnea and 
collapse, ending in death with postmortem evidence of 
asphyxia. 

Baumann found that the thymus contained iodin in 
organic combination, but in much smaller quantity than 
the thyroid. As the thymus atrophies at puberty and its 
persistence after that age is pathological, being associated 



HISTORICAL. 5 

with certain forms of epilepsy, and with Basedow's dis- 
ease it seems improbable that its administration to the 
adult will produce beneficial results. 

Splenic extract has not received much attention. H. C. 
Wood reports three cases of Basedow's disease as being 
benefited by it. It has also been given with benefit in 
cases of melancholia attonita. In leukemia it gave nega- 
tive results. It is on the market as **eurythrol," but pro- 
duces gastric pain and therefore does not permit of con- 
tinuous use. 

Bone marrow from the ribs of young animals has been 
extensively used in anemia without producing satisfactory 
results. Fraser reports its administration as having in- 
creased the hemocytes from 1,869,000 to 3,900,000 and the 
hemoglobin from 38 per cent to 78 per cent in 27 days. 

The pituitary body is an organ which from its ana- 
tomical position would appear to belong to the central 
nervous system. Situated in the sella turcica, it is pro- 
tected from injury, and from its glandular structure and 
large blood supply it should be of importance to the well 
being of the organism. Physiological experiments by its 
extirpation have so far given negative results, and, with 
the possible exception of akromegaly, in which it is usu- 
ally found enlarged, it has not been associated with any 
disease. In animals after thyroidectomy it has been 
found enlarged by Steida, Hofmeister and Gley, but 
whether it is a compensatory hypertrophy has not been 
determined. The administration of its extract has so far 
produced only negative results. Anatomically, according 
to Andriesen, its function would appear to be to take up 
oxygen from the blood stream and to destroy or render 
innocuous the metabolic waste products of the central 
nervous system. Chemically it contains iodin, but in 
very small quantities. The last mentioned writer gives 
the following as the predictable results of its ablation: 



6 THE THYKOID AND PAKATHYBOID GLANDS. 

Malassimilation of oxygen by the nerve tissues with accu- 
mniation of waste products, thus bringing about a nutri- 
tional failure and death of the central nervous system, 
when the following symptoms would be produced, depres- 
sion and apathy, muscular weakness, loss of coordination 
and equilibration, development of twitchings and irreg- 
ular contractions of the muscles, a want of sufficient heat 
production and consequent subnormal temperature with 
wasting of the body tissues. 

Desiccated brain and spinal cord have been used with a 
few reported successes on the principle that in certain dis- 
eases the chemical processes for the formation of the 
specialized substances necessary for the nutrition and 
functionation of the nervous system may be interfered 
with, the administration of the brain and cord containing 
the specialized substances ready formed might supply the 
place of the lost function. Constantine Paul, Babes, 
Gibier, Dana and others report cases of neurasthenia, epi- 
lepsy, bulbar paralysis and chorea as benefited by its use. 
In Mount Hope a very obstinate case of melancholia, 
which had resisted the usual treatment, showed marked 
improvement through its use, but in several other cases 
no improvement was observed. 

The parotid gland has been used in dysmenorrhea with 
reports of success, but the connection is not apparent. 

Glycocholate of soda has been used with success in treat- 
ing diseases of the liver, especially in hepatic colic. None 
of the so-called cholagogues of the Pharmacopeia increase 
the flow of bile, while experiment has shown conclusively 
that the bile salts are the only cholagogue at our com- 
mand. As the bile is an excretion of the liver as well as 
being a necessity for the proper absorption of fats, it is 
of the utmost importance that the quantity should be kept 
at normal. The solvent action of the sodium glycocholate 
on cholesterin and the bile pigments render it of great 



HISTOBICAL. 7 

service in hepatic colic, both as preventing the formation 
of gall stones and also as a solvent for stone already- 
present. It seems from various reports to be of great use 
in torpid liver, acting as a purge for that organ ; also, in 
some cases of chronic constipation, in malarial and post- 
febrile hepatic insufficiency. 

The extract of the suprarenal capsule Jias obtained a 
permanent place in medicine, the active principle adre- 
nalin is used extensively in minor surgical operations as 
a hemostatic ; internally it raises the blood pressure and 
stimulates the heart. 

Extracts of the prostate gland, the liver, the kidney 
and the lymphatic glands have all been tried with nega- 
tive results. 

The thyroid gland has proved to be of the greatest im- 
portance as a regulator of the general metabolism, inter- 
ference with its function producing cretinism, infantilism, 
myxedema and Basedow's disease, while from its power- 
ful physiological action upon the blood-vessels the extract 
or the dried gland is a most valuable addition to the 
Pharmacopeia. 



CHAPTER 11. 

EMBRYOLOGY— ANATOMY— HISTOLOGY— THE 
PARATHYROIDS. 

Embryology.— The thyroid gland is developed from the 
anlages, one median and two lateral, which unite to form 
a common diflferentiation. The median anlage is an in- 
vagination of the floor of the pharynx between the bases 
of the second and first bronchial arches lying between the 
two parts of the tongne and consisting of a small pouch, 
which commences to expand laterally at a very early age 
to form the median duct, the opening of which upon the 
tongue corresponds to the foramen cecum. The duct itself 
is known as the ductus thyroglossus, which persists up to 
the eighth week, gradually elongating as the thyroid and 
tongue separate. The ductus thyroglossus is obliterated, 
but occasionally exists throughout life as the ductus lin- 
gualis. The lateral anlages are derived from the ento- 
derm of the fourth gill clefts ; the fourth entodermal pouch 
develops a ventral prolongation, becoming a closed vesicle 
entirely separated from the pharynx; the vesicle curves 
forward to form round hollow buds. The union of the 
three anlages takes place about the seventh week. His 
records that in a human embryo of the eighth week the 
formation of the hollow acini had begun, and that they 
were lined with epithelial cells, the gland consisting of 
two globes connected by a narrow isthmus. 

Anatomy.— The thyroid body is a highly vascular gland, 
consisting of two lobes, an isthmus and pyramid, situated 
between the second and sixth tracheal ring, covered an- 
teriorly by the sternohyoid, omohyoid and sternothyroid 
muscles, while the sternocleidomastoid also overlaps it. 

8 



ANATOMY. 



The posterior surface is concave and rests on the trachea 
and larynx, covering the recurrent laryngeal nerves. The 




Fio. 1. — The position of the thyroid after removal of the muscles, 
(v. Eiselsberg.) 

lateral lobes cover the carotid arteries; are conical in 
shape, extending from the fifth or sixth tracheal ring to 



10 THE THYKOID AND PARATHYKOID GLANDS. 

the side of the thyroid cartilage covering the inferior 
corners and adjacent portions of the alas. The isthmus 
usually lies across the second and third rings of the 
trachea, but is inconstant in shape and position^ often 
being entirely absent. From the isthmus or from the 
adjacent portions of one of the lobes a slender conical 




Fig. 2. — Absence of the isthmus. Fig. 3. — Isthmus with large pyramid. 
(Marshall.) (Marshall.) 

process ascends upward to the hyoid bone called the pyra- 
mid or middle lobe. Occasionally it is attached to the 
hyoid bone by fibrous or muscular tissue, so that it follows 
the movements of the vocal organs. In front the pre- 
tracheal fascia extends from the isthmus and adjacent 
portions of the lateral lobes to the front of the cricoid 
cartilage, the lower border of the thyroid cartilage form- 
ing a distinct anterior ligament. Each lobe is further 



ANATOMY. 



11 



attached by a firm band of fibrous tissue, the lateral liga- 
ment, to the side of the cricoid cartilage and to the first 
t\«ro or three rings of the trachea. Each lateral lobe meas- 
ures about 50 mm. in length by 30 mm. in width by 18 mm. 
in thickness at its largest part. The isthmus measures 
neariy 12 mm. and from 6 mm. to 18 mm. in thickness. 
The weight of the gland varies very much with age and 





Fig. 4. — Double pyramid. 
(Marshall.) 



Fio. 5. — Absence of isthmus with 
pyramid on left side. (Marshall.) 



in different countries. Virchow places it at from 30 to 60 
grms. ; Schaefer in England from 30 to 40 grms. Wells, 
of Chicago, gives the average weight of 60 glands removed 
in that city as 22 grms. ; the gland decreases in weight as 
age advances. The average weight in persons over 45 
years of age in Wells' series was only 16 grms., while in 
persons from 20 to 45 the average was 25 grms. The 
gland appears to be smaller in females than in males, 
increasing in size during pregnancy and menstruation. 



12 THE THYKOID AND PAKATHYROID GLANDS. 

Usually the lateral lobes are not perfectly symmetrical, 
the left being most often the larger of the two, while the 
isthmus and pyramid vary in size, may be entirely absent 
or fused into one or other of the lateral lobes. The pyra- 
mid occurs, according to Streckiesen, in 104 out of 153 
cases or about 68 per cent. Marshall only found it in 24 
out of 60 cases or 40 per cent. Out of the 104 of Strec- 
kiesen 's cases it was glandular up to the hyoid bone in 55, 
in 12 it was connected to the bone by fibrous tissue, in 2 
by muscle. These muscular fasciculi, which occasionally 
descend from the hyoid bone to the gland or to its pyra- 
mid, are known as the levator glandute thyroidsB. The 
fibers are mostly derived from the hyoid muscle, but occa- 
sionally are independent. 

The arteries of the gland are the superior thyroid from 
the external carotid, the inferior thyroid from the thyroid 
axis of the subclavian and sometimes the thyroidea ima 
from the arch of the aorta. They are remarkable for 
their anastomoses and large size. They terminate in a 
capillary network upon the outside of the acini. The 
veins which are also large form a plexus from which the 
superior middle and inferior thyroid veins are formed on 
each side. The superior and middle thyroid veins open 
into the internal jugular, the inferior veins form a plexus 
in front of the trachea and empty into the innominate 
veins. 

The lymphatics of the thyroid body form numerous 
large anastomosing trunks, both at the surface and 
throughout the substances of the organ. They originate, 
according to Frey, in the connective tissue which unites 
the gland vesicles, with the cavity of which they appear 
not to be in communication. Hiirthle has, by using in- 
termittent pressure, caused injection fluid to pass into the 
vesicles by the lymphatics. Colloid substance is at times 
found in the lymphatics similar to that found in the ves- 



ANATOMY. 



13 



icles, which appears to pass between the epithelial cells 
into the interstitial connective tissue and thence into the 
lymphatics.. 

The nerves are derived from the middle and inferior 
cervical ganglia of the sympathetic and accompany the 
blood vessels. Accord- 
ing to Andriesen there 
are no ganglionic cells in 
their course, their branch- 
es extending close to the 
base of the epithelium 
cells. 

Accessory thyroids are 
common, being formed by 
detachments of small por- 
tions of the gland in the 
embryonic stage, and by 
division of the pyramidal 
process. They may be 
found anywhere between 
the arch of the aorta and 
the hyoid bone, some- 
times even within the 
bone itself. 

Anomalies are common, 
either the pyramid or the 
isthmus may be absent or 
both, the isthmus occa- 
sionally passes behind the 
trachea, one lobe or both 
may be absent. These 
deviations from normal 
are permitted by the fact that, unlike most parenchyma- 
tous glands, the location of its secreting structure bears 
no relation to any fixed outlet or duct. 




FiQ. 6. — ^The thyroid arteries, 
(v. Eiselsberg.) 



14 THE THYROID AND PABATHYEOID GLANDS. 

Histology.— The texture of the thyroid gland is firm, 
appearing granular to the naked eye ; it is invested by a 
thin transparent layer of dense areolar tissue which con- 
nects it with the adjacent parts, imperfectly separating 
its substance into small lobules of irregular form and size. 
When the organ is cut into a yellow glossy fluid, colloid, 
escapes from the cut surface. Imbedded in its substance 

are multitudes of closed ves- 
icles, which are held together 
in groups or imperfect lobules 
of areolar tissue. The wall 
of each vesicle consists of a 
simple layer of cubical or col- 
umnar epithelial cells, which, 
according to Langandorflf, are 
of two kinds, viz : those which 
are actually secreting the ma- 

Normai thyroid gland. ^^^^ Contained in the vesicles, 
colloid cells, and other re- 
serve cells which may take the place of the colloid cells 
or which may become detached and mingle with the 
secretion. Both Langandorfif and Hiirthle agree in sta- 
ting that the secretion is formed partly by exudation from 
the cells and partly by their complete transformation into 
colloid substance. Bozzi describes three classes of cells, 
chief cells, colloid cells and cells undergoing retrograde 
metamorphosis. The chief cells are the most numerous 
and contain highly refractive bodies which he considers to 
be colloid substance ; they also contain finer bodies, which 
are probably incompletely formed colloid, but Babes and 
others state them to be the pigment from the destroyed 
red corpuscles ; fat globules and protoplasm granules are 
also present. The cells appear not to have a distinct 
membrane, but to blend with one another, the outer ends 
resting on the basement membrane. The colloid cells are 




THE PARATHYBOIDS. 15 

smaller than the chief cells and lie in irregular groups 
between the chief cells from which they are probably 
derived; they possess a nearly homogeneous protoplasm, 
more deeply colored, not unlike the colloid substance in 
appearance; they vary in shape, some appearing round or 
oval, with the protoplasm almost destroyed, its remains 
collected around a central mass which appears to be colloid 
containing characteristic vacuoles, the nucleus being at 
one side ; they also group together so as to resemble folli- 
cles; sometimes free colloid is found between the cells. 
The cells showing retrograde metamorphosis have no col- 
loid mass, the nucleus loses its staining properties and 
gradually becomes indistinct, the granules are smaller and 
the protoplasm contains colloid in droplets not running 
together to form a mass ; these cells are formed when the 
follicles fuse together and seem to be due to nutrition 
degeneration. 

Embryonal rests are also found mostly near the capsule, 
but also scattered around in the connective tissue having 
large nuclei with a small amount of protoplasm, they do 
not appear to develop when the gland is partially removed. 

The method of colloid formation has not yet been set- 
tled. Virchow was of the opinion that it was first formed 
indirectly by the cells in so far that the secreted mucoid 
fluid was changed into colloid. Hiirthle claimed to have 
seen droplets of colloid in the cells, and that the cells in- 
creased in size on the formation of the drops, concluding 
that the colloid arose from the protoplasm of the cells. 
Langhans, Langandorff, Gutkneckt and others are of the 
opinion that the cells themselves are transformed into 
colloid. 

THE PARATHYBOIDS. 

The parathyroids consist of two pairs of small glandular 
masses, first described by Sandstrom in 1880, constant in 
man and other mammals, always lying in close proximity 



16 



THE THYROID AND PARATHYROID GLANDS. 



to the lateral lobes of the thyroid body. They vary in 
size from 3 mm. to 15 mm. in diameter with an average 
of about 6 mm. ; are flattened and of a reddish color, some- 
what like the thyroid itself. In structure, however, they 
differ from the thyroid proper, being composed of solid 
masses of epithelial-like cells, which often appear to be 

in sections, arranged in an- 
astomosing columns with 
numerous convoluted blood 
vessels between them. Con- 
nected with the cell masses 
there are frequently lymph 
follicles, differing complete- 
ly from the thyroid and not 
to be confounded with the 
accessory thyroids. Ac- 
cording to Gley they repre- 
sent embryonic portions of 
the true gland, and if left 
after the removal of the lat- 
ter they are able to develop 
further and take on the 
functions of the main organ. 
It is thus he accounts for 
the failure to obtain in some 
animals the usual results of 
thyroidectomy. This is, 
however, denied by Edmunds, although they appear 
to increase in size after the operation and to act vicari- 
ously to some extent. Kohn states that there is one 
parathyroid (outer epithelial body) constantly present in 
mammals on the lateral surface of each lateral lobe and 
another on each mesial surface (the inner epithelial body). 
Associated with these are small bodies of adenoid tissue 
which have the characteristics of thymus gland including 




Fig. 8.— The position of the para- 
thyroid glands. (Zuckerkandl.) 



THE PARATHYROIDS. 17 

the epithelial rests or corpuscles of Hassel and which tend 
to blend insensibly with the neighboring interstitial tissue 
of the thyroid. According to Pienant the tissue of the 
parathyroids is similar in appearance and structure to that 
of the carotid glands and is not embryonic thyroid tissue. 
He states that they take their origin from the fourth inner 
bronchial cleft of the embryo from which also part of the 
thymus and the lateral rudiments of the thyroid are de- 
rived, whereas the main portion of the thymus and the 
carotid glands are derived from the third cleft. 

The theory that the parathyroids are embryonic tissue 
is hardly tenable, from the fact that they develop in chro- 
nological advance of the thyroid. It must also be con- 
sidered that they resemble the suprarenal, the anterior 
pituitary and the carotid glands, which must be looked 
upon as adult tissue. In structure they seem to be made 
up of entodermal epithelial cells, separated by capillaries, 
suggestive of the suprarenal. This is most noticeable in 
compensatory hypertrophy, but, as Edmunds points out, 
there are no acini and no secretion of colloid substance. 
Gley has recently taken up the position, supporting it by 
physiological experiment, that the parathyroids are glands 
sui generis and have a specific function related to that of 
the thyroid. Welch describes the parathyroids as being 
completely invested by a fibrous capsule and either con- 
nected with the thyroid gland by a pedicle of fibrous tissue 
or situated within the body of the gland, but always com- 
pletely separated from it by connective tissue. From the 
deep surface of its fibrous capsule irregular septa are 
given off, dividing the gland into irregular lobules. 
Clusters of fat cells are generally present along the course 
of the vessels and of the connective tissue septa within 
the gland to which the yellow tint is probably due. 

The parathyroids are of epithelial structure and are 
composed of two distinct kinds of cells. The principal 
2 



18 THE THYROID AND PARATHYROID GLANDS. 

cells have a relatively small homogeneous protoplasmic 
body, which takes on basic anilin dyes in varying degrees 
of intensity, and a relatively large pale nucleus with an 
open chromatin network. They constitute the greater 
part of the gland tissue. In their arrangement they show 
at least four different types: (1) a continuous uniform 
cell mass; (2) a continued cell mass, interrupted at fre- 
quent intervals by strands of 
connective tissue, so that on 
section the strands appear to 
be surmounted by epithelial 
cells; (3) a series of anasto- 
mosing columns of cells in a 
vascular fibrous reticulum, so 
that on section the epithelial 
cells appear as discrete mass- 
es completely surrounded by 
FiQ. 9.— Normal Parathyroid vascular Connective tissue; 
^^^^^' (4) groups of small acini, 

each containing a small mass of colloidal material in its 
lumen and lined by a single layer of epithelial cells. It 
seldom happens that a parathyroid is composed of cells ex- 
clusively arranged in one type. The second kind of cell is 
oxyphilic, having relatively to the principal cells a large 
granular protoplasmic body, the granules of which are 
highly oxyphilic, with a small darkly staining nucleus and 
densely arranged chromatin. These cells are not always 
present. There are three types of disposition: (1) a 
uniform cell mass, sharply defined from the principal cells 
and situated either deep in the substance of the gland or 
immediately beneath its capsule; (2) a few columns of 
cells which gradually mix with the principal cells; (3) a 
single acini lined with oxyphilic cells containing a colloid 
lobule in the lumen. Welch considers that the para- 




THE PABATHTBOIDS. 19 

thyroids resemble the anterior lobe of the pituitary body 
more than the suprarenal and that it is unlike thyroid 
tissue ; that the colloid material does not represent a higher 
stage of glandular development, but is rather retrograding 
or degenerative in its nature. 



CHAPTER III. 
PHYSIOLOGY. 

The early physiologists looked upon the thyroid gland 
as having no essential function, probably from its having 
no duct by which its secretion could be conveyed to the 
general system, and from its variable size, position and 
shape, it was stated to be for the purpose of rounding 
out the neck, as having some connection with sleep, as 
influencing the voice, that it acted as a reservoir for the 
blood regulating the brain supply. The connection of the 
gland with the organs of generation had very early at- 
tracted the attention of the laity. In Southern Italy it 
has long been the custom for the parent to measure the 
circumference of the daughter's neck before and after 
marriage, an increase in size being considered as an evi- 
dence of conception. 

It was not till 1859 that systematic investigations as to 
the function of the gland were commenced. Schiff per- 
formed thyroidectomy on dogs and found that they in- 
variably died, and therefore the gland was necessary to 
life. A. and J. Eiverdin described the symptoms pro- 
duced by thyroidectomy, Ord followed in 1878, and then 
Kocher on the same lines, stimulating Schiflf to further 
experiments. Schifif reported in 1884 that the extirpa- 
tion of the gland was not only followed by death to the 
animal, but that it also produced spasms and convulsions, 
which were prevented by the implantation of the gland 
under the skin or in the peritoneal cavity. These experi- 
ments were the commencement of an enormous amount 
of work by a large number of scientists in every country, 

20 



PHYSIOLOGY. 21 

resulting in a number of different theories as to the physi- 
ology of the organ, many of which have been proved to 
be erroneous and are now of little interest except to the 
historian. 

The function of the thyroid gland is said to commence 
'*in utero,'^ or soon after birth (Wolfler). Horsley con- 
siders that it commences before birth, but is greatest dur- 
ing the period of growth, lessening as the vital processes 
decline. He bases his opinion on the decrease of the 
secretory power of the gland in phthisis, in which the col- 
loid substance gradually disappears and the epithelial 
cells pass into the embryonic state, from the fact that 
removal of the gland is more fatal in young than in older 
animals, and that it decreases both in size and activity in 
old age. Nielsen is of opinion that the gland is concerned 
in the change of mucoid into connective tissue during the 
fetal months. 

The writer has analyzed the thyroid glands of several 
children who died immediately after birth, and also a few 
prematurely bom, and has never been able to find a trace 
of iodin or of the blood pressure reducing substance. In 
children of two and three weeks old who had died of 
cachexia, no iodin was found. The earliest age at which 
he found iodin was three months. There is a remarkable 
difference between the calf and the human fetus. In the 
former the thyroid gland contains iodin in utero. As it 
has been shown that thyroglobulin is excreted by the 
mammary gland, with the milk in the human, the child 
receiving in this manner the necessary amount for its 
metabolism, it seems possible that one of the reasons why 
the human infant is so dilBScult to raise on artificial food is 
the absence of the necessary amount of thyroid secretion 
in the artificial food. As the calf is bom with a function- 
ating thyroid, cow's milk probably does not contain the 
amount of thyroid secretion necessary for the development 
of the infant. 



22 THE THYROID AND PARATHYROID GLANDS. 

The function of the gland has been studied chiefly by 
the indirect method of observing the symptoms after re- 
moval of the gland from animals, and some cases in man, 
where the operation was performed for disease. In the 
early experiments the importance of the parathyroids was 
not recognized, and consequently the symptoms were the 
result of the removal of both thyroid and parathyroids, 
which has caused much confusion, being further compli- 
cated by the different results obtained with different ani- 
mals—in some instances as in the rabbit— due to the para- 
thyroids being some distance from the thyroid and not be- 
ing removed in the operation with the thyroid. Ewald 
came to the conclusion that birds survived the operation ; 
that rodents and herbivora generally survived with no 
marked effects, and that in aged dogs the symptoms were 
usually light. Reptiles, young carnivora, monkeys and 
man invariably die after the operation if it is completely 
carried out. Horsley, in 1891, divided animals into four 
classes: (1) birds and rodents, in whom no cachexia was 
produced; (2) ruminants and ungulates, in whom the 
symptoms developed slowly; (3) man and monkeys, in 
whom the cachexia was certain but the symptoms mod- 
erate; (4) carnivorous animals, in whom the cachexia was 
most severe and rapid. These results seemed to show 
that the food habits of the animals had some bearing on 
the importance of the gland to the system, viz : that car- 
nivora were the most affected, graminivorous and com 
eating animals the least affected, while the omnivora occu- 
pied a middle position. The later experiments of Hof- 
meister, de Quervain, Gley and Edmunds have shown that 
there is little or no difference, provided that the whole 
of the thyroid, accessory thyroids and parathyroids are 
removed. 

The symptoms produced by the extirpation of the gland 
are of particular interest from their resemblance to vari- 



PHYSIOLOGY. 23 

ous observed pathological conditions in man, and have 
been the means of recognizing many obscure diseases as 
being the result of cessation or perversion of function of 
the glands. 

In dogs, after the removal of the gland, the first most 
noticeable symptom is a derangement of the functions of 
the medulla oblongata, consisting in vomiting and dys- 
phagia. The efforts of vomiting are accompanied by 
salivation, often preceding an attack of convulsions lasting 
till the animal dies. The vomited matter consists of bile 
and mucus; anorexia is often present, and when the re- 
fusal to take food is absolute it is a sure sign of a rapidly 
fatal result. Sometimes the animal preserves the appetite 
but finds great difSculty in taking nourishment, owing to 
the continuous spasmodic contractions of the masseter and 
the fibrillar contractions of the muscles of the tongue. 
Moreover, the dysphagia usually present renders it as 
difficult to swallow fluids as solids, and if by chance any 
food does enter the stomach it is immediately rejected, 
with an increase of convulsive movements, the animal 
finally ceasing to make any attempt to take food. Vomit- 
ing occurs even when the food is carefully introduced with 
the tube. In a few instances the animal continues to eat, 
but the food accumulates in the stomach, the abdomen 
becomes distended and the large intestine fails to dis- 
charge its contents. Trophic disturbances may appear in 
the form of excoriations, especially affecting the region 
of the articulations in the fore and hind limbs, which may 
suppurate, never showing any inclination to heal. Mus- 
cular paresis and partial paralysis occur usually among 
the earlier symptoms, the extensors in particular being 
affected, causing the staggering gait which is usually very 
marked. Spasms are of frequent occurrence, which, in 
the first instance, affect the masseter and temporal mus- 
cles, but soon spread to the muscles of the body, and seem 



24 THE THYBOU) AND PABATHTBOID GLANDS. 

to be the result of discharges which take place at regular 
intervals. This condition lasts for two or three days, 
whon a violent general convulsion may occur, with a tend- 
ency to tetanus. At this period the respiration is greatly 
inoroasod, in some cases being as high as 220 per minute, 
litv^th often supervening in one of these convulsions. Co- 
iiu^ident with increase of respiration comes increase of 
toininnuture, 42.0 degrees C. and even 43.6 degrees C. 
l^»;u ing Innm observed. In the intervals between the at- 
t;^^ks the temperature has been observed to fall 4 degrees 
Ivlow normal. 

h\ lSvS7 Munk made the statement that dogs survived 
operations which deprived them of the functions of the 
U\\nud gland, provided the wound healed well, but if 
jkwelling of an inflammatory or edematous nature, or a 
swelling dependent on hemorrhage or upon accumulations 
\\( the secretions of the wound occurred, the animals died 
with eliaracteristic symptoms. Munk performed the op- 
oration of isolation of the gland by doubly ligating and 
dividing the veins of the gland. He then lifted the lobes 
out of their capsules and completely severed them from 
tluMr connections with the body of the animal by ligation 
of tlio vessels and nerves of the hilus, returning the lobes 
to th(»ir original position. Nine dogs survived his experi- 
nuMits which were repeated and confirmed by Boginski. 
Ilalstead suspecting that Munk had overlooked the acces- 
Hory glands and also small portions of the main gland, 
w(»nt over the same ground in the most complete manner, 
(hiding that his suspicions were correct. He found that 
when the gland was perfectly isolated death ensued with 
the usual symptoms, which varied somewhat in different 
animals, the most regular being conjunctivitis, trismus, 
persistent erection of the penis, fibrillary tremors of the 
tongue and of the muscles generally. He then experi- 
mented with partial isolation, which he brought about by 



PHYSIOLOGY. 25 

ligating all the vessels except the thyroid artery, which 
supplies the upper lobe and the vein from the lower lobe. 
The symptoms thus produced were not identical with 
those occurring in complete isolation. The most constant 
were tongue tremors, licking movements, anemia, con- 
junctivitis, general tonic and clonic spasms, inflammation 
of gums, with occasionally a falling out of the hair, accom- 
panied with an itching of the skin, producing an edema- 
tous appearance not unlike myxedema. This latter symp- 
tom only occurred when the wound did not heal by first 
intention. He next experimented with piecemeal removal 
of the gland and observed that the same symptoms were 
produced, the amount of gland removed in order to pro- 
duce them varying in different dogs, probably on account 
of the size and number of the accessory glands and to 
individual peculiarities, one dog doing well and remaining 
in good health with only one-eighteenth of the gland re- 
maining. During the experiment a female who had had 
the left and the lower third of the right lobe removed was 
impregnated by a healthy unoperated dog. She gave 
birth to eight puppies, whose thyroid glands were at least 
twelve times larger than normal. It is remarkable that 
in this case and also in a similar one that a few hours 
before whelping the symptoms of complete thyroid de- 
privation manifested themselves although each animal 
possessed much more thyroid than was actually required 
for her wants. It had previously been observed that 
tetany had appeared previous to labor in cases with con- 
genital thyroid insufficiency. These experiments have 
been repeated recently with the same result by Edmunds 
and are suggestive. It would be interesting to observe if 
an excessive secretion or administration of thyroid during 
pregnancy would not produce a reduced thyroid in the 
produce, which, if it took place, might account for some 
cases of sporadic cretinism. 



26 THE THYROID AND PABATHYBOID GLANDS. 

Horsley divides the symptoms of thyroidectomy into 
those of over action and of want of action. The first 
symptom of over action is fibrillar muscular tremor, re- 
sembling tetany. The individual contractions of the 
muscles follow one another in monkeys at the customary 
rate of clonus, viz : eight to ten per second. Summation 
next occurs, tetanoid spasms follow and finally rigidity 
and contraction. Symptoms of want of action are motor 
paralysis and anesthesia^ the toxemic condition producing 
functional neurosis, epilepsy, hemiplegia, etc. Tissue 
changes are also marked, emaciation of an acute form, 
with mucin in the connective tissue. If, however, the 
cretinoid condition supervenes there is no increase of 
mucin, but fibroid changes occur, coupled with emaciation. 
Virchow suggests that the edema characteristic of myxe- 
dema is a metaplasia of the subcutaneous fat into mucus, 
with an increase of volume ; the skin becomes coarse and 
dry from the absence of secretion ; the subcutaneous tissue 
thickened and inelastic ; the hair falls out, becoming thin 
and gray. Disorders of temperature also occur. The 
intrinsic changes, viz: the modifications which are intro- 
duced into the normal heat balance off the subject after 
elimination of the traumatic factor, consist of a rise of 
from 4 degrees to 5 degrees during the acme of the mus- 
cular twitching. The coincidence of this rise in tempera- 
ture with the nerve disturbances suggests that it may be 
dependent on a derangement of the heat controlling cen- 
ters. Before death the temperature is subnormal. Ex- 
ternal heat has a great effect on the operated animal, ex- 
ternal cold precipitating the symptoms. Animals which 
were apparently in good health while kept in a high tem- 
perature developed the characteristic symptoms at once 
on being exposed to cold. 

The blood changes show a connection between the gland 
and the blood metabolism. Normally the leucocytes are 



PHYSIOLOGY. 27 

present in a greater proportion in the veins than in the 
arteries of the gland, and this projx^rtion is greater than 
that found in the veins of the limbs. After thyroid- 
ectomy there is an increased venosity of the blood, with a 
great diminution of the amount of oxygen. This decrease 
of oxygen in the arterial blood may be so great as to be 
less than the oxygen in normal venous blood, a condition 
which would account for many of the symptoms. 

If a portion of the thyroid gland be removed there is 
a compensating hypertrophy of the remaining part which 
undergoes histological changes, the cubical cells become 
columnar, the vesicles become oblong or branched and the 
colloid substance becomes more watery, changes which 
are almost identical with those found in the gland in Base- 
dow 's disease. These changes are not affected by division 
of the sympathetic. Schiff found, after destroying the 
sympathetic nerve fibres accompanying the blood vessels 
to one lobe, that the lobe remained identical in minute 
structure. Horsley tried similar experiments with re- 
spect to the recurrent laryngeal nerve with the same re- 
sult. Katzenstein could find no difference in the two 
lobes after stimulating one and not the other. Edmunds 
excised the superior laryngeal nerve and a considerable 
length of the vasosympathetic lower down on the same 
side, thus any secreting fibres passing by the recurrent 
laryngeal nerve would be cut off. On this side the thyroid 
lobe was not touched or even seen. On the other side the 
lobe, together with the parathyroids, was excised. Of the 
ten dogs experimented upon three died in one, two and 
three days. No symptoms occurred, but death appeared 
to be due to the operation, as the thyroid lobe was found 
to be almost free from colloid and the secreting cells mul- 
tiplying into the vesicles. Seven of the dogs lived longer, 
six showing symptoms; one, howeter, was operated on 
again after twenty-eight days without having shown any 



28 THE THYROID AND PABATHYROID GLANDS. 

symptoms. One was allowed to live 242 days, dying with 
athyroidal symptoms. Another was killed at the end of 
271 days suffering from severe symptoms. The other 
four were operated on a second time. The pathological 
findings in these cases varied somewhat. In one, in which 
the lobe was removed by a second operation, the gland was 
devoid of colloid, the cells multiplying into the cavities of 
the vesicles. In another, which had well marked tremors 
but recovered, the gland was found to be much enlarged, 
weighing 3.5 grms., or about three or four times larger 
than normal. The colloid had disappeared, the increase 
in size being due to growth of young tissue between the 
vesicles, the secreting cells were not multiplying into the 
vesicles. The animal which lived 242 days, dying with 
severe symptoms, had a normal gland and a normal para- 
thyroid. In the animal killed after 272 days there were 
some normal vesicles, but there were also vesicles filled 
with multiplying cells from which the colloid had wholly 
disappeared. 

Hiirthle has experimented on the effect of the stimula- 
tion of various nerves by the faradic current on the secre- 
tion of the gland, and has had negative results from both 
the laryngeal nerves and the vasosympathetic. On the 
contrary, G. A. Schaefer found that the cells of the thy- 
roid show the same changes as those of other glands after 
the injection of pilocarpine. As pilocarpine only pro- 
duces its effects by nerve stimulation it follows that the 
secretion of the thyroid must be influenced by the stimula- 
tion of some nerve or nerves. Hiirthle suggests that the 
stimulation of the gland is due to the presence of certain 
unknown substances in the blood, and states that tying 
the gall duct in dogs produced homogeneous globules in 
the epithelial cells and lymph spaces of the gland, which 
showed the same inclination to solidify and gave the same 
staining reactions as the follicular colloid substance, prov- 



PHYSIOLOGY. 29 

ing that the passing of certain constituents of the bile 
into the blood produced increased secretion of the gland, 
and that any nervous influence that may exist is not cen- 
tral, but is due to the ganglia either in or in the imme- 
diate neighborhood of the gland, and further, that the 
enlarged gland of Basedow's disease is not primarily of 
central origin. 

Sandstrom discovered the parathyroids in 1880, and in 
1881 Cresswell Baker independently also observed the 
glands but did not recognize them in animals, describing 
them as undeveloped portions of the thyroid gland. In 
1884 Horsley identified and described the parathyroids, 
but they were not thoroughly studied till 1892, when Gley 
published a set of papers recording his experiments. 
Under the name of ''glandules thyroidiennes" he de- 
scribed in the rabbit two glands, one on each side of the 
trachea, situated at some distance below the thyroid, so 
that in previous operations for thyroidectomy in that ani- 
mal these glands had probably not been removed. In the 
dog, on the contrary, the corresponding structures were 
so closely incorporated with the outer surface of the lat- 
eral thyroid lobes that they must have been almost in- 
variably removed with the thyroid. On account of these 
different anatomical arrangements he suggested the causes 
for the relative insusceptibility of the rabbit to thyroid- 
ectomy; he removed both the thyroids and the parathy- 
roids from a series of rabbits with the result that in the 
majority of cases acute symptoms and speedy death en- 
sued. Further, he found that the removal of the thyroid 
alone, leaving the parathyroids in situ, produced in the 
dog and the rabbit little or no result. At the time of these 
experiments (1892) the existence of the internal para- 
thyroids was not known, and Gley's work only applies to 
the external parathyroids. No really accurate knowl- 
edge of the position of these glands was published till 



30 THE THYROID AND PABATHYBOID GLANDS. 

1895, when Kohn's elaborate monograph on the thyroid 
gland of the cat demonstrated the fallacies underlying all 
previous operations. He found that in the cat, dog, rab- 
bit, and probably in other mammalia, there were four 
parathyroids, and he further showed conclusively that 
these bodies were not thyroids but were independent spe- 
cific structures, naming them ''the external and internal 
epithelial corpuscles of the thyroid." 

In 1896 Vassali and Generali published the result of 
their experiments. They removed all the four parathy- 
roids, leaving the thyroid in situ in ten cats and in nine 
dogs. Of the cats nine died by the tenth day, while one 
was living at the end of a month. All the dogs died 
within eight days, the symptoms in both cats and dogs 
being the same as those previously recorded as the result 
of thyroidectomy. As a rule, however, conclusive attacks 
were absent or only very slight, but on the other hand, 
the phenomena of diminished nervous excitability pre- 
dominated in the form of paralysis, which rapidly killed 
the animal. Rouxeau performed on the rabbit what Vas- 
sali and Generali had done on the dog and cat, viz: he 
removed the four parathyroids, leaving the thyroid intact. 
The results were not uniform, but he concludes that re- 
moval of the parathyroids is much more serious than re- 
moval of the thyroid alone in the rabbit. Moussu comes 
to the conclusion that the functions of the thyroid and 
parathyroids are different ; that suppression of the thyroid 
produces only chronic symptoms, while the suppression 
of the parathyroids induces acute symptoms. He also in- 
duced experimental cretinism in the dog, cat, and birds 
by the removal of the thyroid, the parathyroids being left 
intact. Welsh, after a number of very careful experi- 
ments, comes to the following conclusions: (1) Removal 
of all four parathyroids in the cat leads to acute and severe 
symptoms, with a rapidly fatal issue, even though the thy- 



PHYSIOLOGY. 31 

roid be retained practically uninjured. (2) Removal of 
three parathyroids does not lead to death, but may cause 
transient symptoms similar to those which result from 
removal of all the glandules; loss of two parathyroids 
does not produce any appreciable result. (3) Removal 
of the thyroid and some of the parathyroids may lead to 
death with acute symptoms, if only one parathyroid is 
left, but may not induce any obvious derangement if two 
parathyroids are retained, at least not for several months. 
(4) Administration of fresh parathyroid by the mouth has 
no effect, either in mitigating the symptoms or in averting 
death after removal of the thyroid and parathyroids in 
the cat, even though relatively enormous doses are given. 
In 1898 Edmunds published the results of his very elab- 
orate experiments as to the functions of the parathyroids, 
of which the following are the most important. In two 
dogs about one quarter of one lobe and the external para- 
thyroids were left, the rest being removed. Neither of 
these dogs showed any symptoms during the nine and 
twenty-six days they were allowed to live. In two other 
dogs the upper part of the thyroid was left on each side, 
with the addition that in each a length of the vasosym- 
pathetic was removed on one side. One of the dogs suf- 
fered from tetany, rigidity of the limbs, tremors, emacia- 
tion, and a trophic lesion of the skin, in the second dog 
the only symptom was emaciation ; twenty-nine days later 
the remaining portion of the gland was removed, the dog 
dying with the usual symptoms. In eight dogs one ex- 
ternal parathyroid was left and only just sufficient thyroid 
to avoid interference with the blood supply. The dogs 
had no symptoms, except that one of them became thin. 
Three of these dogs were subsequently killed and the 
parathyroids identified by microscopical examination. In 
the other five it was attempted to remove the parathyroids 
during life. In two this was successfully accomplished, 



32 THE THYBOID AND PABATHYBOID GLANDS. 

with the result that the animals had the usual symptoms. 
In the other three dogs the part removed proved not to be 
parathyroids and no symptoms resulted, the parathyroids 
being found on postmortem examination. In seven other 
dogs it was intended to leave the external parathyroids, 
but microscopical examination proved that the tissue left 
was not parathyroid, all three dogs dying with the usual 
symptoms. As dogs live when the parathyroids are left 
and die when it is subsequently removed, or when only a 
small piece of thyroid proper is left instead, it seems evi- 
dent that the excision of the parathyroids is the cause of 
the acute symptoms, tremors, rigidity, convulsions, dysp- 
nea and death, which follow the total excision of the 
thyroid and parathyroids, and further it suggests that 
the excision of the thyroid proper only causes the symp- 
toms of myxedema. In four rabbits, from which the 
thyroid was removed, leaving the parathyroids, the health 
failed, the hair fell out, edema occurred in the lower part 
of the face, followed by death. Vassali and Generali 
have found that if all the four parathyroids in the dog are 
excised and the whole of the thyroid left the dog will die 
with the usual symptoms in a few days, while if one of 
the parathyroids is left and the whole of the thyroid re- 
moved the animal will live. Gley found that if the whole 
of the thyroid proper and one parathyroid were removed 
in rabbits the animal would live, but if the remaining 
parathyroids were excised the rabbit would die with the 
usual symptoms. In dogs in which a single parathyroid 
was left and a minute piece of the thyroid no symptoms 
of any kind appeared, even after five months. The ani- 
mals were kept so long in order to see if the parathyroids 
developed into thyroid tissue. They did not, but the cells 
became more definitely arranged in rows, small collections 
of secretion were seen and the trabeculae of connective 
tissue were much thickened. 



PHYSIOLOGY. 33 

In order to obtain an obvious case of myxedema, the 
whole of the thyroid gland was removed from four mon- 
keys. In the first there was muscular weakness, the hair 
fell out extensively from the front of the chest and there 
was some swelling about the face, but only temporarily. 
Four and a half months after the operation a well-marked 
edema occurred in the face but quickly passed away, and 
in six and a half months the monkey was well. The other 
three monkeys died with the usual symptoms. The fail- 
ure to obtain true myxedema in these cases was appa- 
rently caused by the animals dying from the nerve symp- 
toms before the myxedema had time to develop. Four 
other monkeys were operated upon as before and treated 
with thyrocoUoid, prepared according to Hutchinson's 
method. The first monkey died in six days in spite of 
treatment, and the second had slight symptoms on the 
first day which passed off. On the twenty-seventh day 
the treatment was stopj^ed, three days later symptoms ap- 
peared but passed off, when treatment was renewed, the 
animal, however, dying on the forty-first day. The third 
monkey had no symptoms from the first; the treatment 
was stopped on the sixteenth day ; on the twenty-first day 
symptoms appeared, treatment was resumed, the symp- 
toms disappeared, and five months after the operation the 
monkey was well. In the fourth monkey symptoms ap- 
peared on the third day and the monkey died on the 
seventh day in spite of treatment. Though three out of 
four of the monkeys died yet treatment had some effect. 
Edmunds summarizes the results of his experiments, com- 
ing to the following conclusions: (1) the parathyroids of 
dogs have as much or more to do with saving them from 
acute myxedema as the thyroid proper; (2) although the 
extract from the thyroids of sheep may keep off and re- 
lieve the symptoms in thyroidless monkeys it will not, as 
a rule, save their lives; (3) a parathyroid will not by 

8 



34 THE THYROID AND PARATHYROID GLANDS. 

process of compensatory hypertrophy develop into thyroid 
tissue; (4) the mortality was 44 per cent after total ex- 
cision of the parathyroids, and after excision of both thy- 
roid and parathyroids the mortality was 80 per cent, even 
with thyroid feeding; (5) the symptoms produced by the 
excision of the parathyroids are the same as by the com- 
plete operation (thyroid and parathyroids), viz: tremors, 
a slow and unstable gait, passing into paralysis of the 
hind limbs, emaciation and muscular weakness. 

The microscopic changes found in the thyroid lobes in 
cases of excision of the parathyroids are marked in these 
cases which survive the operation a few days. There is 
a diminution in the amount of colloid in the vesicles, the 
vesicles themselves becoming oblong and branched, the 
secreting cells columnar or multiply so as to fill the cavity 
of the vesicle and there is an excessive amount of young 
thjToid tissue between the vesicle. Edmunds considers 
these changes to be identical with those described as com- 
pensating hyi^ertrophy of the thyroid and with the 
changes found in Basedow's disease; there is, however, 
an apparent decrease in the size of the gland. 

In two of the dogs, after partial parathyroidectomy, 
there were marked eye symptoms. Auld and others have 
noted eye symptoms after thyroid feeding, Beclere re- 
porting a case where a patient, partly by mistake, took 60 
grms. of sheep's thyroid in a week, which was followed 
by thyroidismus and a certain amount of exophthalmos. 
Edmunds performed a number of experiments to investi- 
gate the point, the subject being of great importance from 
the possibility of its offering an explanation of the pathol- 
ogy of Basedow's disease. 

Total thyroidectomy was performed on ten monkeys, 
five of whom had had thyroid feeding before the opera- 
tion. Of the five which had no thyroid feeding two 
showed narrowing of pali)ebra] fissure, one at first widen- 



PHYBIOLOGV. 



33 



ing, followed by narrowing, and in two no change. Of 
the five which had thj^roid feeding, in two there was 

r€xophthahiios witli widening of the fissures; in one nar- 
rowing, and ill two no change. In another monkey no 
operation was performed, but it was fed with large doses 
of an extract equal to about half a sheep's thyroid per 
diem* A considerable widening of the palpebral fissurei^ 
resulted, with ])erliaps some protrusion of the eyeballs. 
Edmunds, in further 
experiments on six 
monkeys fed with from 
a ba!f to three whole 
aheeps ' thyroids per 
day, prQdueed prop- 
tosjs, dilatation of the 
pupils, widening of the 
palpebral fissure, erec- 
tion of the hairs of the 
head, falling out of the 
hair in patches, paral- 
ysis of one or more 
limbs, emaciation and 
muscular weakness, 

L followed by death from 
asthma. The average 
life of the monkeys 
after the commence- 
ment of the treatment was seventj^-six days. Microscopic 
examination of the thyroids and of pituitary glands were 
made, but no pathological condition could be detected. 
Shortly before death the animal showed an objection to 
light and to being looked at. 

As the effect of thyroid feeding on the eye might be 
produced by action on the central nervous system, com- 
municating with the cervical sympathetic or by local action 




Fiii. 10. — Monkey in telajik' utlnrk aftet 
pxtirpation of thyrmd* (v. Eifselslwrgj 



36 THE THYROID AND PARATHYROID GLANDS. 

on the ganglia in and about the eye, the cervical sympa- 
thetic was divided on one side in two monkeys and the 
animals fed in doses corresponding to about three sheeps' 
thyroids per day. In twelve days the eyes on the unop- 
erated side were seen to be more prominent and the palpe- 
bral fissure wider than before treatment ; the eyes on the 
operated side also became very wide and prominent. A 
considerable length of the nerve was removed to prevent 
the probability of repair. This experiment isT)orne out 
by a case reported by Boissou. The patient, a girl of 
twenty years old, was submitted to resection of the cer- 
vical sympathetics, first on one side and then on the other^ 
for Basedow's disease. Notwithstanding the operation 
the exophthalmos continued and became so severe that the 
eyes could not be closed, the cornea sloughed, sight was 
lost, the patient dying in a short time. 

This case and Edmunds' experiments show that the 
cervical sympathetic is not the main factor in producing 
the protrusion of the eyeballs, and it also seems probable 
that thyroid extract acts partly through the cervical sym- 
pathetic and partly locally. Experiments were also made 
on rabbits, with the thyroid with the two smaller parathy- 
roids removed. In one rabbit the eyes became more promi- 
nent and remained so ; in one no change was observed for 
nine months, when the eyes began to get narrow, becoming 
very narrow before death. The cervical sympathetic was 
excised on both sides to see if it produced further narrow- 
ing; in two the eyes became very narrow before the ani- 
mals died, which occurred in two or three days ; in three 
the eyes narrowed and the animals lived, and in one there 
was no change. The thyroids of the four surviving rab- 
bits were excised, the two larger parathyroids being left 
intact. In one there was a marked increase in the nar- 
rowing, in the other two no immediate effect, but the ani- 
mals died ten months later with verv narrow eves. In the 



PHYSIOLOGY. 37 

rabbit in which division of the sympathetic had produced 
no symptom, the excision of the thyroid was followed by 
death in three days with narrow eyes. 

In further experiments to observe the effect of the ex- 
cision of the parathyroid on the eye, Edmunds excised 
both cervical sympathetics in a rabbit, which caused nar- 
rowing of the palpebral fissures ; later he excised the thy- 
roid together with the two smaller parathyroids, leaving 
the two large parathyroids. This operation produced no 
further narrowing. In five rabbits he excised the two 
larger parathyroids, leaving the thyroid intact, together 
with the two smaller parathyroids. In four animals the 
eyes became somewhat wider for a time, reverting to nor- 
mal ; in one there was no change. In six rabbits the op- 
posite operation was performed, namely, the two larger 
parathyroids were left intact and the thyroid lobes with 
the two smaller parathyroids were excised. The results 
varied, in three of the rabbits it was noticed that the eyes 
for a time were wider than normal, four of the rabbits died 
and, at the time of death, their eyes were much narrowed ; 
two were killed at a time when the eyes were normal. 

Edmunds summarizes his results as follows: 

(1) That after complete excision of the thyroid and 
parathyroids the great majority of dogs die within a few 
days and cannot be saved by thyroid feeding, but a small 
minority survive even after the complete operation. 

(2) In operations in which one or more parathyroids 
are left the dogs as a rule survive. 

(3) That when only the thyroid is left they die as a rule. 

(4) That with respect to operations that paralyze the 
secretory nerves of the thyroid the dogs often die, al- 
though possessed of the whole of one thyroid lobe, to- 
gether with the parathyroids of the same side, or even as 
in Halstead's experiments when possessed of the whole 
thyroid. 



38 THE THYROID AND PARATHYBOID GLANDS. 

(5) With respect to the microscopical appearances of 
the parts left in the experiments, the parathyroids seem 
merely to hypertrophy, and they do not change into thy- 
roid tissue proper. The thyroid tissue may remain un- 
altered even though the dog may die of athyroidic symp- 
toms, or it may materially alter and this in one or two 
days ; either the colloid diminishes or entirely disappears, 
vesicles enlarge and the lining membrane becomes con- 
voluted. This may occur to such a degree as to present 
appearances closely resembling, if not identical with, 
those in a papilloma, or the colloid may disappear, the 
vesicles may retain their shape and the round cells may 
multiply into and fill the cavity of the vesicles, thus pro- 
ducing an appearance somewhat similar to that seen in 
carcinoma, but though much hypertrophy sometimes oc- 
curs nothing of the nature of invasion has been seen. 

(6) In the central nervous system changes have been 
found corresponding to paralytic symptoms, the lesions 
that occur are observed mainly in the large cells, varying 
from chromatolysis of the Nissl granules to a complete 
destruction of the cells. 

(7) In the eyes of monkeys, dogs and rabbits he finds 
that when an animal is dying of athyroidic symptoms, 
whether after a complete or only partial extirpation, there 
is, as a rule, narrowing of the pali)ebral fissures. After 
the removal of the parathyroids a condition of widening 
of the eyes occurs, which coincides with the view that 
Basedow's disease is connected with the parathyroids. 

Moussu has experimented with the parathyroids and 
comes to the conclusion that the acute convulsive attacks 
in thyroidectomized animals are due to the parathyroids 
having been removed, and that if operated dogs are given 
the watery extract of from twelve to twenty horses' para- 
thyroids the convulsions are arrested. He further states 
that myxedema is not helped by the administration of 



PHYSIOLOGY. 



39 



parathyroid (confirmed by Charrin), but that he has seen 
improvement in a case of Basedow's disease by the injec- 
tion of the extract of eight horses ' parathyroids per diem. 
He sums up that the removal of the thyroid, leaving the 
parathyroids produces myxedema in man and perhaps 




Fio. 11. — A 4 months old kid whose thyroid wan removed at 21 days 

old. (v. Eiselsberg.) 
Fig. 12. — Control animal from the same birth, (v. EiHelsberg.) 

also in swine and dogs; in other species progressive ca- 
chexia. In the young of man, swine, goats, dogs, cats and 
birds it produces cretinism, which is improved by the 
administration of thyroid. That the removal of the para- 
thyroids in carnivora i>roduccs death, which was formerly 
attributed to the absence of the thyroid, and that the par- 



40 THE THYROID AND PARATHYROID GLANDS. 

tial removal of the parathyroids produces symptoms sim- 
ilar to Basedow's disease, it has not been shown as yet 
that the parathyroids are diseased in Basedow's disease, 
nor that feeding with parathyroids will benefit the patient. 
A few eases are recorded, but as yet the benefit of the 
treatment must be regarded as ^'not proven." 

There seems to be no doubt that the two sets of glands 
are not wholly independent, for the removal of the thy- 
roids causes changes in the parathyroids, and the excision 
of the parathyroids changes in the thyroid. One very 
attractive theory suggests itself, that the sjTnptoms of 
myxedema are due to the failure or removal of the thyroid, 
while removal or failure of the parathyroids produces the 
tremors and other nervous symptoms, with the general 
symptoms of Basedow's disease. If the failure of the 
parathyroids causes hyi3ertrophic changes in the thyroid, 
as shown by Edmunds, it may be supposed that the in- 
creased secretion of the altered thyroid would cause ex- 
ophthalmos, and thus we should have, as in Basedow's 
disease, tremors, exophthalmos, etc. Edmunds states that 
excision of the parathyroids produces sometimes exoph- 
thalmos, sometimes enophthalmos, and exophthalmos can 
be converted into enophthalmos by the removal of the 
thyroid lobes. Total thyroidectomy in the monkey is 
usually followed by enophthalmos, exceptionally exoph- 
thalmos, while thyroid feeding produces exophthalmos in 
monkeys, as a rule. 

Prof. Freiherr v. Eiselsberg experimented with the re- 
moval of the thyroid in young animals. He removed the 
thyroid from two lambs at ten days old, keeping another 
as control. In a month the control animal was much 
larger than the operated lambs, and at six months the 
control animal was as heavy as both the other operated 
lambs together. It weighed 35 kg., compared with 10 kg. 
and 14 kg. Not only was the physical growth arrested^ 



PHYSIOLOGY. 



41 



but the mental condition was very evidently defective, and 
there was also a want of coordination. At the autopsy 
there was calcification of the aorta, which had the appear- 
ance of being due to senile changes and not to inflamma- 
tion. He operated on young goats, pigs, rabbits and asses 
and found the same results, namely, arrest of physical and 
mental development, comparable to cretinism. 




FiQ. 13.-— Lamb, 6 months old, the thyroid being removed on the 
tenth day. (v. Eiselsberg.) 

The influence of the thyroid secretion on the morphol- 
ogy of the organs of generation in both sexes has been 
demonstrated by many observers. It is an ancient tradi- 
tion that the thyroid enlarges at the first menstruation, in 
certain women, each period producing an appreciable en- 
largement of the gland. There seems also to be a bal- 
ancing as it were between the flow of blood and the gland. 
A suppression of menstruation often produces a swelling 
of the gland, which disappears on the reostablishment of 
the flow. There is also a very remarkable connection 
pointed out by Gautier that the menstrual blood contains 



42 THE THYROID AND PARATHYROID GLANDS. 

iodin and arsenic, both of which substances are a part of 
the normal secretion of the thyroid. In girls it has often 
been stated that the first sexual act produces an enlarge- 
ment of the gland. There seems to be no connection be- 
tween the thyroid and the sexual act in the male, it having 
never been observed to swell after the first coitus but en- 
larges about the time of puberty and occasionally a pal- 
pable goitre may form. The enlargement of the gland 
during the rut has been observed in the dog, cat, rat, sheep 
and deer, and was described by Wagner in 1858. 

The eflfect of the thyroid development on puberty is of 
great importance. Broca ( ' * Goitre and Cretinism, ' ' 1891 ) 
states that in the complete cretin puberty is never estab- 
lished. The reproductive functions are nil and sterility is 
absolute, while arrested development of the sexual organs 
is almost a constant symptom of infantilism. Occasion- 
ally there are cases of hyperthyroidea occurring at pu- 
berty, which Brissaud explains as a result of a difficult 
sexual metamorphosis, or, in other words, that an arrested 
development of the sexual organs may produce thyroid 
derangements. In cretinism, and especially in infantil- 
ism, the increase in the development of the sexual organs 
under thyroid treatment is very marked. It is of im- 
portance, from a therapeutic standpoint, to note that the 
increase in size of the thjToid gland is anterior to the 
development of the sexual organs, the secretion of the 
gland being increased, the surplus is utilized to stimulate 
growth, and, therefore, if the gland does not increase, 
])uberty does not occur and the growth is retarded, pro- 
ducing infantilism. 

During pregnancy there is a marked modification of 
the gland. Freund observed augmentation of volume in 
forty-five out of fifty women. Lange established that the 
enlargement commenced about the fourth month in pri- 
miparas and the fifth month in nmltiparas. The gland 



FHYSIOUiGT. 



4a 



commences to diiuiuish sevifn or eight days after eonHiie- 
ment and quickly recedes to normal; sometimes the hyper- 
trophy continues through lactation. Lange found that out 
of 133 cases 25 did not show any hypertrophy; examina- 
tion sliowed that 20 of these presi*nted alhunrinuria, and he 
argued that the relative insufficiency of the thyroid has an 
influence on the kidney* lOxperimentation confirmed his 
theory- Lange removed four-fifths of the thyroids in a 




number of cats, producing no i^yni{)toms except in those 
with young, the latter dying and the autopsy showing fatty 
degeneration of the kidney. Several of the operated cats 
were impregnated, developing albuminuria and the kidney 
degeneration. This experiment shows a possibility nf 
eclani|KHia being connected with byixithyroidea. 

The thyroid has also some effect ujion the production 
of milk. iL Wauters experimented upon a cow who, for 
fifteen days, liad averaged 11.5 litres of milk per day- 
He gave 6 grms. of frc*^h thyroid for ten days, during 



44 THE THYROID AND PARATHYROID GLANDS. 

which time the average amount of milk rose to 12.55 litres. 
On the following eight days he gave 8 grms. thyroid and 
the milk rose to 13.8 litres per diem. The average quan- 
tity of milk during the twenty days the animal was under 
treatment was 13.17 litres, being an increase of 1.67 litres 
per day. 

Lange took nine hens eighteen months old and gave one 
of them from 10 to 30 grms. of thyroid daily. During 
the following twenty-eight days the eight hens laid forty- 
two eggs, or an average of 5.25 eggs, while the hen receiv- 
ing thyroid laid during the same period sixteen eggs ; the 




Fig. 15.— Aorta of thyroidectomized sheep showing atheroma. 
(v. Eiselsberg.) 

weight of the eggs also increased 10 grms. Lange had 
previously observed that a thyroidectomized hen laid an 
egg with a very thin shell weighing onlj^ 5 grms. 

Metabolism experiments have been made during the 
administration of fresh thyroid gland, thyroid sicca and 
thyroidin on healthy subjects, in myxedema, in Basedow's 
disease, in obesity and in thyroidectomized animals, which 
give practically the same results. In thyroidectomized 
animals without thyroid feeding there is a greatly in- 
creased elimination of nitrogen and a decreased elimina- 
tion of phosphorus, the latter rising on the administration 
of thyroid. Roos kept a dog under obsei-vation for two 
months, estimating the elimination of nitrogen, sodium 
chlorid and phosphoric acid. He then administered 3.0 



PHYSIOLOGY. 45 

grms. and later 6.0 grms. thyroid sicca daily. There was 
an increased elimination if nitrogen, sodium chlorid and 
phosphoric acid. He then removed the thyroids and con- 
tinued the administration of the thyroid sicca, the nitrogen 
and sodium chlorid elimination was further increased, but 
the phosphoric acid was diminished. The nitrogen elim- 
ination in the unoperated atiimal rose from 3.04 to 3.8 and 
from 3.4 to 4.15 and in the operated animal from 3.61 to 
5.35. Magnus Levy found that the amount of oxygen 
utilized by a subject at rest was 3.1 to 5.36 ccm., while in 
the obese it was only 2.82 (v. Noorden found 2.64). By 
the administration of thyroid he could raise the used 
from 2.26 to 2.36 on the fifteenth day and to 2.55 on the 
nineteenth day, the loss of weight in the nineteen days 
being 4 kg. Theile and Nehrung raised the from 2.87 
to 3.43, or 20 per cent; v. Noorden raised the used 21 
per cent, which lasted fourteen days after the thyroid 
feeding was suspended. Magnus Levy treated a myx- 
edematous patient with thyroid tablets, thyroantitoxin and 
iodothyrin. With the tablets the patient lost weight from 
42 to 39.2 kg., the pulse rose from 60 to 120, temperature 
from 36.2 to 37.5, the used from 1.22 to 2.15, the respira- 
tion quotient sank from 0.85 to 0.71. With FraenkePs 
antitoxin the amount of used was not increased nor did 
the pulse rate increase, the body weight did not fall but 
increased 1 kg. The iodothyrin produced about the same 
effect as the tablets, the rose from 1.3 to 1.98, the respi- 
ration quotient fell from 0.83 to 0.74, the pulse rate rose 
from 60 to 100, the body weight fell from 44.2 to 41.9 kg. 
Stiive found the used increased in a healthy subject by 
the administration of thyroid tablets 20 to 23 per cent, 
while the increase of COo eliminated was somewhat less. 
Voit arrived at the same conclusions. 

Venehren experimented with three normal young men, 
giving 0.1 to 0.3 iodothyrin per diem and found no change 



46 THE THYROID AND PABATHYBOID GLANDS. 

in the nitrogen elimination, but in two older subjects there 
was a marked increase. Dennig found that the nitrogen 
elimination was increased on the administration of thyroid 
sicca. Blubtreu and Wendelstaat, in a metabolism experi- 
ment on the latter, found that by taking three to four 
tablets, equal to about 2 grains thyroid sicca each, he lost 
3 kg. in weight and 15.97 nitrogen, equal to 500 grms. 
muscle substance, therefore 16 per cent of the loss of 
weight was due to loss of muscle substance. Scholz found 
that by taking three tablets daily his case lost no weight. 
Before taking the tablets the elimination showed a nitro- 
gen retention + 3.7567, while taking the tablets the nitro- 
gen retention was reduced to + 2.6399. Richter found in 
the period before administration of the thyroid an N re- 
tention -f 4.95, during the experimental period +3.22, 
and during the after period +4.0. Gluzinski and Lem- 
berger obtained about the same results by the administra- 
tion of tablets, but on giving the fresh gland the retention 
N of + 2.1 was reduced to — 1.48, showing that while the 
subject lost 1 kg. weight he lost 6.24 grms. N, equal to 200 
grms. muscle substance, or 20 per cent of the total loss 
was, therefore, muscle substance. Richter, in order to 
see if it were possible to reduce the weight without loss 
of nitrogen, put a subject on a diet containing 20.07 N 
and equal to 2988 calories, or 40 calories per kg. of body 
weight. He gave ten, fifteen and twenty thyroid tablets 
two days each. The subject lost 2 kg. in five days with 
a nitrogen retention of + 12.89, showing that under suflS- 
ciently nitrogenous diet it is possible to reduce weight 
without loss of muscle substance. In this case the only 
change noted in the urine was an increase of xanthin 
elimination. 

Schorndorff, in a most elaborate and carefully con- 
ducted metabolism experiment on a dog 25 kg. weight in 
nitrogen equilibrium, found that on the administration of 



PHYSIOLOGY. 47 

thyroid the elimination of nitrogen was increased during 
the first eight days by 1.59 grms. per diem. The elimina- 
tion then sank to equilibrium, then rose to slight minus 
and then again fell to equilibrium. The total nitrogen 
taken was 729.13, eliminated 731.96 equal to a loss of 0.1 
grm. per diem. He next increased the amount of thyroid 
in order to see if after the elimination of the fat the in- 
creased oxidation would cause increased loss of nitrogen. 
During twenty-two days the animal received 729.93 N and 
lost 760.51 N equal to 927.0 grms, muscle substance; the 
dog had lost in all 2200 grms. weight, and had, therefore, 
lost 1273.0 grms. fat; this loss was equal to 40.0 grms. 
muscle substance and 55.0 grms. fat daily. Contrary to 
other observers he found that as soon as the thyroid feed- 
ing ceased the excessive nitrogen elimination ceased, the 
animal gaining weight rapidly. He concluded that the 
increased elimination of nitrogen in the first few days of 
thyroid feeding is due to the elimination of extractive sub- 
stances, while the fat metabolism really spares the proteid 
nitrogen. When the body fat has been reduced to a cer- 
tain point the nitrogen elimination is increased by the 
oxidation of proteid. 

The effect of thyroid feeding upon the metabolism is 
the result of increased oxidation and consequent loss of 
weight. The intake of oxygen is increased, the carbon 
dioxid given off is increased, the nitrogen elimination is 
increased. In the first few days, probably by the elimina- 
tion of extractives, it is possible, by proper diet, to prevent 
any loss of nitrogen, the loss of weight being then due to 
the oxidation of the fat and loss of water. The chlorid and 
phosphoric acid elimination are also increased, uric acid 
elimination is not affected, but a slight increase in the 
xanthin bodies has been observed, the total quantity of 
urine is usually increased. There is also quite a percep- 
tible increase of perspiration which, if very marked, may 
cause the urine to decrease in quantity. 



48 THE THYROID AND PARATHYROH) GLANDS. 

The administration of thyroid in large doses produces 
a condition known as thyroidismus, resembling in many 
points the symptoms of Basedow's disease. Exophthal- 
mos has been observed by Notthaft in the case of a patient 
who took very large doses for obesity. The resemblance 
to Basedow's disease was so marked that the diagnosis of 
Basedow's disease was made before the real cause was 
discovered. The tremors, mental depression, rapid pulse, 
diagnostic of Basedow's disease, are almost invariably 
produced by overdoses of thyroid. Ewald gives a de- 
tailed account of the symptoms observed in various cases. 
The pulse rate is increased to 100-120 or higher, palpita- 
tion of the heart, stenocardiac attacks, rise in temperature, 
a feeling of weakness with constriction of the chest, 
tremors, insomnia, increased diuresis but, if the sweating 
is very profuse, the twenty-four hours' urine may be re- 
duced to 300 ccm. or less, with increased elimination of 
nitrogen, chlorids and phosphoric acid, and may con- 
tain albumin ; the respiration is accelerated, headache and 
rheumatoid pains occur, eructations, loss of weight and 
complete anorexia, thirst, dizziness, loss of consciousness, 
increased flow of saliva, pruritis, urticaria, erythema, ec- 
zema; the heart may become so weak and the vessels so 
dilated that the patient will keep his head below the level 
of the heart. Sugar has been observed in the urine by 
Dale, Jones, Ewald, Bennig and others. It occurred in 
one case at Mount Hope. Levulose and inosite have both 
been recorded as occurring. The mental symptoms are 
usually those of depression. The writer took 24 grs. per 
diem for three days for experimental purposes, and the 
depression was so great that the experiment could not be 
continued. In other cases there is a precordial anxiety 
with an ill-defined but very real fear of impending danger. 
Maniacal symptoms occur, usually of a melancholic type, 
and suicidal tendencies may appear. 



PHYSIOLOGY. 49 

The action of thyroid feeding on the heart and circula- 
tion has been studied by Oliver, Schaefer, Gley, Langlois, 
Gurnard and Martin. They find that the pulse becomes 
weak and rapid. Oliver, by means of his hemodynamo- 
meter and arteriometer, showed that the blood pressure is 
very markedly reduced, while the arteries and arterioles 
are dilated, especially the peripheral vessels, producing 
the perspiration. Gurnard and Martin showed that, after 
the vessels had been dilated and the heart weakened by 
the injection of thyroid extract, they could be rapidly 
restored to normal by the injection of suprarenal extract. 

The blood changes after thyroidectomy are more constant 
than any other pathological findings and oflfer an explana- 
tion to most of the symptoms produced by the operation. 
Horsley, Herzen and Rojwitsh found that the blood be- 
came more venous, the former showing that the arterial 
blood might contain less oxygen than was normal in venous 
blood. Alberti and Tizzoni found that the in the ar- 
terial blood was reduced from 7 to 8 vol. to 8 to 11 vol. ; 
Vassali propounded the theory that the red corpuscles lost 
their power to combine with oxygen, and found that when 
he injected the expressed fluid from a gland into the veins 
of an operated dog, whose venous blood was almost black, 
after a few hours the blood became normal in color. 

As was previously mentioned it has been observed that 
operated animals react to external temperatures very 
readily ; the formation of COg is immediately increased on 
their being brought into the cbid, which* diily takes place 
after some time in nontial animals. This points to a vaso- 
motor disturbance. Schaefer has shown that the intra- 
venous injection of thyroid extract reduces blood pressure, 
and Oliver that the calibre of the radial artery is increased 
at the same time. Lewy made a careful examination of 
the blood in operated animals and found that the specific 
gravity was always reduced, but that no other verj^ con- 
4 



60 THE THYROID AND PARATHYROID GLANDS. 

stant changes existed; further, that no relation appeared 
to exist between the severity of the symptoms and the 
anemic changes; normally the leucocytes are present in 
greater proportion in the veins than in the arteries of the 
gland, and the proportion is greater than that found in 
the limbs. Formanck and Haskovic found the number of 
red corpuscles invariably reduced and the leucocytes in- 
creased, the total solids and iron were diminished. Duc- 
ceschi found that in operated dogs before the commence- 
ment of the convulsion the serum albumin increases and 
the serum globulin decreases, the total proteids vary from 
the commencement of the convulsions to the death of the 
animal, the globulin continues to increase, and the serum 
albumin and total albuminoids decrease as in starvation. 
Bottazzi finds the same changes as Ducceschi; also that 
the red corpuscles part with their hemoglobin very readily, 
lose in specific gravity and that there is an increase in 
fibrin. Masoin claims to have found a toxin in the blood 
of operated animals as well as in the urine; Zuntz and 
Geppert found acid substances in the blood; Gley found 
that the blood serum of operated animals produced typical 
symptoms when injected into the blood of normal animals; 
Edmunds and Baldi on the contrary could obtain no symp- 
toms under the same conditions. 

Excess of mucin has been found in the blood of myxe- 
dematous patients and in that of operated animals. Halle- 
burton analyzed the blood tissues and organs of a case of 
myxed^W ; 'the- tissues w^^ ftnelt minced, weighed and 
usually kept a day in metliyr kieohol, decanted and the 
tissues treated with lime water or dilute barium hydrate 
solution, allowed to macerate for a few days, strained, and 
the mucin precipitated from the filtrate by the addition 
of weak acetic acid, filtered through a weighed filter, 
washed with alcohol and ether, dried at 100 degrees C. 
to a constant weight and weighed. 



PHYSIOLOGY. 51 

By this method a number of analyses have been made 
with varying results. 

The skin of the thigh of a still-bom child contained 
0.96 per cent mucin ; the abdominal skin of children from 
seven weeks to nine years of age 0.39 to 1.02 per cent, 
with an average 0.766 per cent; skin from the same part 
in grown people contained 0.11 to 0.64 per cent, with an 
average of 0.385 per cent; in connective tissue 0.5 per 
cent; in Achilles tendons 0.298 to 0.77 per cent; in the 
parotid gland only a trace. In a patient who had sujffiered 
for ten years from myxedema Cranston Charles found 
fifty times more mucin than normal in the skin of the 
foot. Halleburton found 0.81 to 0.72 per cent, and once 
0.012 per cent, average 0.374 per cent; the quantity in 
the tendons was increased, 1.42 per cent in the heart, 1.65 
per cent in the spleen, 2.21 per cent in the lungs, 0.7 per 
cent in the parotid. In the blood which clotted imper- 
fectly there was no mucin found, neither in the peri- 
cordial, peritoneal or cerebro-spinal fluids. Horsley and 
Halliburton (Brit. Med. Jour., 1885) found that in 
monkeys, after the extirpation of the gland, mucin was 
increased in the tissue as shown by the following table: 

Sub- 
Skin. Tendons, Muaclc. Parotid, maxillary. Blood. 

Normal 0.089 0.009 

7th day after operation . . 0.045 0.09 trace 0.016 trace 

29th " " .. 0.108 0.15 0.208 1.036 trace 

49th " " .. 0.23 0.24 trace 0.17 0.33 0.08 

55th " " .. 0.312 0.255 trace 0.072 0.0 0.35 

It was also noted that the blood coagulated very slowly, 
but that the proportions of serum globulin to serum albu- 
min were normal. It was further observed that pigs did 
not become myxedematous on thyroidectomy and that 
there is a quantity of mucin in normal pigs' tissue, the 
skin contained 0.209 per cent, tendons 0.403 per cent, 
muscle none, parotid trace, submaxillary gland 0.416 per 



52 THE THYBOID AND PABATHYBOID GLANDS. 

cent, blood none, pancreas 0.009. In sheep, on whom the 
operation had no apparent effect until they were turned 
out in the cold, the urine became thick with mucus when 
the symptoms appeared. Byrom Bramwell has observed 
this symptom in patients suffering from myxedema. 
Halliburton concludes from the above analyses that the 
percentage of mucin in the tendons of myxedematous 
patients slightly exceeds normal, but that excess of mucin 
in the tissues is not pathognomic of the disease. He re- 
ports one case in which the mucin was very excessive. 
Wagner claimed that by the injection of mucin into the 
vessels of cats he produced tremors and tetanoid spasms 
resembling those of thyroidectomy. 

The pathological findings in tliyroidectomized animals 
are not marked nor constant, and seem to be the result of 
starvation rather than toxemia. In the nervous system 
various writers have found a number of lesions but none 
occur with sufficient regularity or uniformity to permit 
them to be considered as pathognomic of the condition. 
In the central nervous system anemia and edema of the 
brain and hyperemia with extravasations in the spinal 
cord have been frequently observed. Pisenti found cavi- 
ties in the lumbar and costal portions of the cord contain- 
ing only traces of nerve substance, but such cavities are 
often found in hyperemic conditions of the brain and cord. 
In the brain substance a condition of encephalitis paren- 
chymatosis, accompanied by swelling of the nerve cells 
and axis-cylinder; also a small round cell in filtration of 
the meninges of the upper portion of the cord have been 
noted by Horsley and Arthoud. May on found a neur- 
itis vagi. Langhans and Kopp, examining the peripheral 
nerves in the acute cachexia of dogs and in the more 
chronic cases of monkeys, men and cretins, found changes 
of an inflammatory nature. Although no definite constant 
change has been observed in the nervous system there can 



. PHYSIOLOGY. 53 

be no doubt that the symptoms are of central origin. 
Schiflf has shown that the tetanic convulsions ceased on 
section of the nerve trunks ; Lang cut the sciatic nerve in 
an operated dog and saw the twitching cease in the muscles 
supplied by the nerve ; Horsley and Lang cut the cord at 
the eighth vertebra and saw the twitching almost cease in 
the extremities. The motor area of one hemisphere was 
removed by Horsley in five operated dogs, the twitchings 
were more marked on the side which was intact. The re- 
sults of these experiments prove that the disturbances are 
of central and not peripheral origin. 

Zesas and Crede and also Lemke found that the spleen 
became enlarged after removal of the thyroid, and Lohlein 
that after the removal of the spleen the thyroid en- 
larged. Zanda claimed that if the spleen was removed 
four weeks the thyroid could be removed without causing 
any symptoms, and argued that the spleen produced toxic 
substances which it was the function of the thyroid to 
neutralize. Fano on repeating Zanda 's experiments did 
not confirm his results. Hofmeister, Albertoni, Tizzoni, 
Gley and de Quervain failed to confirm Zesas and Crede 's 
observations, and found in five cases of men dying of 
cachexia strumipriva that the spleen was unusually small 
in four cases and of normal size in one. Lang in over 
forty experiments failed to show any connection between 
the spleen and the thyroid. 

Gley found that by extirpating portions of the thyroid 
at different times in rabbits he could produce hypertrophy 
of the hypophysis cerebri, the weight of the latter being 
increased from 0.02, the average normal weight, to O.lOl 
grms. There has been much speculation as to the possi- 
bility of the vicarious action of the hypophysis for the 
thyroid, which was rendered ])robable by the former oe- 
caaionally containing iodin, but there has been very little 
evidence forthcoming in sui)port of the theory. 



54 THE THYBOm AND PARATHYROID GLANDS. 

In operated animals the temperature is usually normal 
except during the tetanic spasms, when it may rise 2 to 5 
degrees C, Herzen on one occasion observing a tempera- 
ture of 43.4 degrees C, later the temperature falling be- 
low normal ; it may go as low as 33 degrees C. There is 
marked susceptibility to cold in operated animals, which is 
also very evident in myxedematous patients. Munk, Lang 
and Kocher observed that the patients suffering from 
cachexia strumipriva were more comfortable in warm 
rooms, complaining of cold at ordinary temperature. By 
increasing the external temperature operated animals can 
be kept alive much longer and the cachexia and tetany 
reduced to a minimum. Whether the feeling of cold is 
central in origin or the result of trophic changes of the 
skin has not been decided. 

During the convulsions the respiration is increased, 
between the attacks it is normal or reduced; the type is 
normal. The heart's action is increased in volume. 

The urine shows no very marked change, it is usually 
decreased in quantity, of an increased specific gravity and 
may contain albumin during the convulsions. The tox- 
icity has been found to be increased by Gley and Laulanie, 
who claim that on the injection of the urine of an oper- 
ated animal into the veins of an unoperated animal typical 
symptoms were produced. Alonzo and others have failed 
to corroborate their results and could find no appreciable 
difference. The nitrogen and chlorid elimination is in- 
creased, while the phosphoric acid is decreased, the pro- 
portion of neutral sulphur to total sulphur is also in- 
creased. The increased elimination of nitrogen and 
chlorids is no doubt due to the progressive anemia and 
consequent starvation, while the decreased phosphoric acid 
and increased neutral sulphur may be due to decreased 
oxidation. There is probably some connection between 
the phosphorous metabolism and the thyroid secretion, as 



PHYSIOLOGY. 00 

the effect of congenital absence or early removal of the 
gland produces an arrest of development, especially of 
the skeleton, the long bones and vertebrae suffering the 
most. Hofmeister made exact comparative measurements 
in animals and found that the growth of the long bones 
was decreased one-third. 

The influence of food on the symptoms of thyroidectomy 
is marked. Briesacher found that dogs suffered less and 
could be kept alive longer if fed on well-cooked meat and 
milk, while if given raw meat or meat extract they suc- 
cumbed much earlier. On milk diet the animals lived 
longer or survived in apparently perfect health with only 
one-third to one-fifth of the gland remaining. Herbivora 
seem also to suffer less than the camivora, due presumably 
to their vegetable diet. 



CHAPTER IV. 
CHEMISTRY OF THE THYROID GLAND. 

Since the thyroid has been proved to be a secreting 
organ and of vital importance to the system, the chemical 
nature of its secretion has been the subject of most careful 
research by numbers of physiological chemists, both in 
Germany and England, their efforts having been directed 
to the isolation of the active principle. That the gland 
contained considerable quantities of extractives, viz : xan- 
thin, hypoxanthin, kreatin, kreatinin, paralactic acid, ino- 
site (?), indicating high metabolic activity was early 
proved, but none of these could be looked upon as the 
active principle. White and Davis, working on the hy- 
pothesis that the active principle was a ferment, obtained 
a body which had some activity. Gourlay failed to find a 
ferment which would dissolve mucin, which was consid- 
ered at that time to be the function of the gland, but he 
isolated a nucleoalbumin which produced intravascular 
clotting, and which he claimed existed in the colloid sub- 
stance. Bubnow extracted three different forms of pro- 
teid, one apparently a globulin; Notkin following on the 
same lines isolated a substance which he believed was the 
toxic product of metabolism, which underwent decompo- 
sition in the gland through the action of an h\7)othetical 
enzyme. In 1895 Sigmund Fraenkel isolated a crystal- 
line alkaloid-like body resembling guanidin to which he 
gave the empirical formula C„H,,N..j()fi. Drechsel later 
described a body identical with that of Fraenkel and 
another similar to it. Fraenkel's thyroantitoxin was a 
hygroscoy)ic crystalline substance, soluble in water and 
alcohol, neutral to slight alkalinity and gave the alkaloid 



CHEMISTRY OF THYROID GLAND. 67 

reactions. Injected into animals it failed to produce a fall 
in blood pressure but increased the pulse rate; admin- 
istered to thyroidectomized animals it caused some im- 
provement in their condition. Fraenkel's observations 
have not, however, been confirmed ; the epoch-making dis- 
covery of Professor Baumann of Freiburg, in 1896, of a 
body containing iodin in organic combination in the thy- 
roid of man and of many animals, possessing the physio- 
logical characteristics of the gland, prevented any further 
experiments in that line. Baumann describes the sub- 
stance he isolated, which he named * * thyroidin, " as a 
brownish amorphous compound which decomposed on 
heating, giving off the odor of pyridin, it is insoluble in 
water, sparingly soluble in alcohol but dissolves readily 
in dilute alkalis, being precipitated by acids, it gave no 
proteid reactions, and constantly contained phosphorus; 
he obtained 9.3 per cent iodin in crystalline form from 
this substance. Baumann was unable to complete his 
work, owing to his lamented death in 1897, when physi- 
ological chemistry lost one of its ablest disciples. His 
method for the isolation of the thyroidin consisted in 
digesting the gland for several hours with a 10 per cent 
mineral acid on a sandbath with a return condenser and 
extracting the residue with 90 per cent alcohol. He 
proved that the substance was iodin in proteid combina- 
tion, and he named it thyroid albumin. Drechsel and 
Baumann found that the iodin-containing proteid could 
be dissolved in normal salt solution, which solution he 
diluted with fifteen volumes of distilled water, passed 
carbon dioxid through it, obtaining a precipitate of a 
globulin containing iodin, he added acetic acid to the 
filtrate and boiled, securing a precipitate of albumin which 
also contained iodin, and therefore concluded that there 
were two iodin-containing proteids in the gland, a globulin 
and an albumin. 



58 THE THYBOID AND PABATHYROID GLANDS. 

Oswald extracted 99.5 grms. of human thyroid which 
contained 21.92 mg. iodin ten times with normal salt solu- 
tion, and obtained 17.26 mg. I in solution, being 78.7 per 
cent of the total I; Lambach obtained 97.8 per cent in 
solution ; in neither case was there any iodin in inorganie 
combination. 

Oswald then proceeded by Pick's method to sex>arate 
the albumins and found that the precipitation conmienced 
at 0.26 and continued up to 0.44 saturation, so that at 0.5 
saturation one proteid was completely precipitated, in the 
filtrate precipitation begun at 0.64 and continued up to 
0.82 saturation when the filtrate contained no proteid. 
He found that the first precipitate contained iodin but no 
phosphorus, while the second precipitate contained no 
iodin but contained phosphorus, proving that the sepa- 
ration of the proteids was complete. The first precipitate 
was dissolved in water, filtered and again half saturated 
with ammonium sulphate. This precipitate was dialyzed 
till free from ammonium sulphate, redissolved in alcohol 
(95 per cent), filtered and the precipitate dried. An 
easier method which dispenses with the tedious dialyzing 
is to dissolve the precipitate from the half-saturated am- 
monium sulphate solution in water and precipitate with 
dilute acetic acid, filter, dissolve the precipitate in 0.1 per 
cent sodium hydrate, precipitate with acetic acid, washing 
the precipitate with water acidulated with acetic acid. 

The precipitate is only very slightly soluble in water, 
but is more easily dissolved by the addition of neutral 
salts, is very soluble in dilute alkalis, is precipitated by 
slight acidulation with acetic or hydrochloric acids. Sat- 
uration with sodium chlorid produces only a slight cloudi- 
ness, saturation with magnesium sulphate and half satura- 
tion with ammonium sulphate give complete precipitation. 
These reactions are those of the globulins and Oswald 
designates the iodin-containing globulin as thyroglobulin. 



CHEMISTBY OP THYROID GLAND. 59 

Myosin is precipitated from its solution in neutral salts 
by acids and gives the other globulin reactions, egg and 
serum globulin are not thus precipitated. This substance 
is not pseudomucin, as is often stated, as pseudomucin is 
not precipitated by acids. 

Thyroglobulin is precipitated by sulphuric acid but is 
not soluble in excess. It is also precipitated by phos- 
photungstic acid, phosphomolybdic acid, ferrocyanid of 
potassium, acetic acid, iodomercuric potash, trichloracetic 
acid and by copper sulphate. It gives the color reactions 
for proteids, the biuret reaction, Millon's reaction, Adam- 
kiewicz's reaction, MoUisch reaction and the xanthopro- 
teic reaction. 

The salt free solution becomes cloudy on heating but 
does not coagulate, on the addition of 10 per cent magne- 
sium sulphate it coagulates at 65 degrees C. ; it contains 
sulphur which combines with lead. From the strong 
result of Mollisch's reaction it may be assumed that it 
contains a large carbohydrate group in the molecule; 
after boiling for two hours with 5 per cent solution of 
hydrochloric acid the solution gives the red reaction with 
a-naphthol and sulphuric acid, and also reduces Fehling's 
solution and ammonia silver oxid, while it fails to give the 
typical phloroglucin and hydrochloric acid reaction, it 
gives a brown color with this test, showing that pentose is 
not present; it forms osazone with a melting point of 100 
degrees C. with phenylhydrazin (Hutchinson failed to 
obtain a reducing substance from sheeps' thyroid and 
Reinbach from the colloid of calves' thyroids). In making 
the elementary analysis of his thyroglobulin Oswald used 
the Fresenius method for estimating the iodin, having 
found that the estimation as silver iodid gave too high 
results, owing to the precipitation of silver chlorid. As 
the estimation of the iodin in the preparations on the 
market is of value as an indication of their activity the 



60 THE THYROID AND PARATHYROID GLANDS. 

method is here given: A weighed quantity of the sub- 
stance to be tested is placed in a nickel or porcelain 
crucible with a little water and pure sodium hydrate, 
evaporated to dryness, a little potassium nitrate added, 
then incinerated, the residue dissolved in hot water, fil- 
tered, and the filtrate placed in a well-stoppered bottle 
with about 10 ccm. of carbon disulphid, acidulated with 
sulphuric acid and nitrous acid, the solution is extracted 
several times with carbon disulphid, the iodin is dissolved 
in the carbon disulphid which is washed two or three times 
with water. The titration is then carried out with a solu- 
tion of hyposulphite of soda standardized against a solu- 
tion of potassium iodid of known strength. 

AVlien thyroglobulin is submitted to pepsin digestion for 
four weeks a gray brown flocculent precipitate remains, 
which contains iodin, gives the xanthoproteic reaction but 
neither the biuret, Millon's nor Mollisch's reactions, and 
is precipitated from its solution with phosphotungstic 
acid. Hutchinson, by digesting thyroglobulin prepared 
by his method, obtained a substance which gave no biuret 
reaction but contained 0.8 per cent phosphorus, showing 
that the residue contained nucleoalbumin as well as thyro- 
iodin. Oswald separated the albumoses and peptones in 
the solution from the pepsin digestion by the Pick method 
and found that the protalbumose and deuteroalbumose 
contained iodin in quantity and that the peptone B con- 
tained a small quantity, while the heteroalbumose and 
peptone A contained only faint traces, which were prob- 
ably due to impurities. 

The digestion of thyroglobulin with trypsin for four 
weeks resulted in a clear solution, which only gave faint 
cloudiness with ammonium sulphate, acetic acid produced 
no precipitate, showing that the iodin thyroglobulin was 
completely broken up, though the solution contained iodin 
in organic combination. On concentration of the solution 



CHEMISTRY OF THYROID GLAND. 61 

tyrosin crystals were found and on further concentration 
leucin. This decomposition by trypsin digestion and the 
iodin remaining in organic combination shows that the 
iodin is not combined in the tyrosin group of the thyro- 
globulin molecule. 

Thyroglobulin treated with 10 per cent sulphuric acid 
on the sandbath with a return condenser is split up, 
leaving a brown flocculent residue and a brown colored 
solution, on filtering and washing till the wash water is 
free from sulphuric acid, extracting with boiling alcohol 
till the latter is no longer discolored, the alcohol solution 
evaporated to dryness and dried to a constant weight 
leaves a brownish powder, which is insoluble in water or 
acids but is easily soluble in alkali. It gives neither the 
biuret, Millon's or Mollisch^s reactions but gives the xan- 
thoproteic reaction, contains much iodin and corresponds 
with Baumann's thyroidin. Thyroglobulin is split up 
with concentrated acids and with barium hydrate. 

Oswald proved the physiological effect of the thyro- 
globulin on the metabolism of animals, finding that it in- 
creased the elimination of nitrogen. 

The second proteid separated from the normal salt solu- 
tion of the gland, and which contained no iodin, contained 
0.16 per cent phosphorus, coagulated in a 10 per cent 
solution of magnesium sulphate at 73 degrees C. with 
a-naphthol and sulphuric acid it gave a red color, with 
phloroglucin and hydrochloric acid a brown color, show- 
ing that the carbohydrate group is not probably a pentose ; 
it also contained xanthin bases and is, therefore, a nucleo- 
proteid; further, on being given to animals it failed to 
increase the elimination of nitrogen. 

Oswald made an elementary analysis of the thyro- 
globulin from the glands of man, pigs, sheej), oxen and 
calves : 



C2 THE THYROID AND PABATHYBOID GLANDS. 

Coitus Calvtt 
Man. Svnne. Sheep. Oxen. Goitrous. Normal. 

Carbon 61.85 52.21 52.32 62.45 52.28 

Hydrogen 6.88 6.83 7.02 6.93 7.04 

Nitrogen 15.49 10.59 15.9 15.92 15.99 

lodin 0.34 0.46 0.39 0.86 0.56 

Sulphur 1.87 1.86 1.95 1.83 2.00 

Oxygen (23.57) (22.15) (22.42) (22.01) (21.61) 

Baldoni analyzed the thyroids of calves, sheep, pigs, 
horses and oxen obtained from the slaughter houses in 
Rome: 

/ in dry I in 

Albumin. Olobulin. Nudeoproteid. Gland. GlobuHn. 

Calf 70.58 61.41 4.15 0.842 1.33 

Sheep 63.16 63.58 3.69 0.652 1.16 

Horse 70.6 68.56 4.45 0.677 1.1 

Ox 08.17 68.49 3.43 0.615 1.01 

Pig 04.21 50.46 3.55 0.311 0.58 

These analyses show that the constituents of the thyro- 
globulin in all the animals examined are almost propor- 
tionately the same, while the iodin may vary from 0,0 to 
0.86, as in calves. The calves' glands which contained no 
I were from Zurich and were very large, being from 60 to 
300 grms. in weight; they were not colloid goitres but 
hypertrophied glands in which no* colloid could be seen. 
The glands containing 0.36 iodin were from Paris, their 
average weight being from 15 to 20 grms., showing a con- 
siderable amount of colloid. These analyses of calves' 
glands are of special interest, as they show that the goi- 
trous glands contain a thyroglobulin which has the same 
elementary analysis as in oxen but contains no iodin. 
The thyroglobulin containing no iodin was proved to be 
physiologically inert by Lyon and Oswald, which shows 
that the physiological activity of the thyroglobulin de- 
pends on its containing iodin in the molecule. 

Oswald made the following analyses of the thyroglobu- 
lin of human glands : 



CHEMISTRY OF THYROID GLAND. 63 



•« 



i II* 



From CoUoid Goitres S e i^ 2 -3 -tttf 3 

^""" "^ II § L IIP 

•S| s^ ^^ «| fill 
if ll 1^ 1^ 1^ Mil 

PQ {^ ;5 ;5 Cj !^ R; 

Carbon 52.02 61.77 51.82 51.85 

Hydrogen 6.91 6.71 7.05 6.88 

Nitrogen 15.32 15.09 15.46 15.49 

lodin 0.07 0.19 0.07 0.19 0.18 0.34 0.51 

Sulphur 1.93 1.93 1.83 1.87 

Oxygen 23.75 24.31 23.65 23.57 

These analyses show that the elementary composition 
of the thyroglobulin is the same in men and in animals, 
with the exception of the iodin, and that the latter is vari- 
able both in animals and in men. They further show that 
the thyroglobulin in goitrous glands is less than in the 
normal gland ; that the glands rich in colloid contain about 
twice as much iodin as normal glands; that the relative 
iodin of the thyroglobulin of the glands rich in colloid and 
in colloid goitres is smaller while the absolute iodin con- 
tents of the whole gland is higher. The fact that in the 
thyroglobulin from a case of Basedow's disease where the 
gland was extirpated during life, the percentage of iodin 
is the same as in the colloid goitres from Basel is of par- 
ticular interest ; also that the gland of the patient to whom 
potassium iodid had been administered, which was an 
enlarged gland rich in colloid, contained a much greater 
quantity of iodin than the other Zurich glands and much 
more than the normal glands from Hamburg, which seems 
to prove that the thyroglobulin of the gland is capable of 
combining with the iodin administered by the mouth and 
suggests the possibility that the symptoms of iodism and 
of poisoning with iodoform may be the result of an in- 
creased formation and consequent absorption of thyro- 
globulin containing iodin. Another point of importance 
suggests itself from the analyses that there is in some 



64 THE THYROID AND PARATHYROID GLANDS. 

glands, if not in all, a quantity of thyroglobulin containing 
no iodin, which argues in favor of the theory that the thy- 
roglobulin is secreted iodin free, and that the iodin enters 
into combination with the previously formed thyroglobu- 
lin. Again, has the thyroglobulin any physiological func- 
tion when not combined with iodin? 

The question arises, Does the thyroid contain iodin thy- 
roglobulin only when colloid is present or at least visible 
under the microscope, and if not visible under the micro- 
scope is iodin absent from the gland? If iodin is absent 
from a gland in which no colloid can be found it follows 
that the thyroglobulin must be first excreted from the cells 
before it combines with the iodin and becomes active. 
The results of a number of analyses have apparently 
proved that the amount of iodin bears a direct relation to 
the amount of colloid substance. In a gland which con- 
tained but little colloid the analysis showed that the rela- 
tion of iodin thyroglobulin to the total weight of the gland 
was 1 to 10, while in another, which was full of colloid, 
the relation was 2 to 3; this also proves that by far the 
greatest proportion of the colloid substance is thyroglobu- 
lin; in fact so small is the proportion of nucleoproteid 
that it is possibly only the product of the nuclei of the 
cells which rupture into the follicles of the gland. 

The amount of the total iodin in the glands varies within 
wide limits. Roos analyzed many glands and found that, 
generally speaking, the glands of the true carnivora very 
seldom contain iodin, graminivorous animals always con- 
tain it, rodents usually have it, also omnivorous animals, 
cats have very little. The quantity of iodin in the glands 
of man varies very much according to locality. Weis 
found the average of glands in Silesia averaged 4.04, in 
Breslau 3.8 mg. Oswald found that glands from Geneva 
averaged 9.32 mg. ; Lausanne 7.07 mg. ; Basel, 6.48 mg. ; 
Zurich, 10.27 mg. ; Bern, 13.04 mg. Baumann found that 



CHEMISTRY OF THYBOID GLAND. 



65 



in Freiburg they averaged 2.5 mg.; Hamburg, 3.8 mg.; 
Berlin, 6.6 mg. Eosetzki found in Styria an average of 
3.21 mg.; lolen in Sweden 3.08 mg.; Wells in Chicago 
10.79 mg. During fetal life and early childhood iodin is 
absent pr only present in traces. Wells found in Chicago 
as much as 0.076 mg. in a child four weeks old, 0.532 mg. 
at four years old and 3.19 at seven years of age. Wells, 
in a number of analyses from Chicago, tabulates the 
following : 













Weight qf 


Iodin Per 


Total Iodin 


Sex. 


Age, 


Onue qf Death. 


Gland. 


Gram in Mg. 


inMg. 


Female. 


. . .term 




0.135 


trace 


trace^ 


Male... 


. . .'term 




0.465 


trace 


trace* 


Female . 


. . .term 




0.73 


trace 


trace* 


Male... 


. . . 4 weeks 


Lobular pneumonia 


0.68 


0.11 


0.076 


Male... 


...4 


weeks 


Meningitis 


0.18 


0.42 


0.076 


Male... 


...4 


years 


Diphtheria 


0.58 


0.92 


0.532 


Female . 


...7 




Phthisis 


1.61 


1.98 


3.19 


Male... 


..45 




Chronic nephritis 


2.6 


2.86 


7.47 


Male... 


..60 




Brain tumor 


4.39 


2.64 


11.75 


Male... 


..60 




Tubercular peritonitis 


2.59 


1.67 


4.33 


Male... 


..36 




Pneumonia 


3.88 


2.58 


10.00 


Male... 


..35 


II 


Peritonitis 


3.84 


2.66 


10.21 


Male... 


..45 


ti 


Pneumonia 


10.59 


0.99 


10.47 


Male... 


..44 


« 


Pneumonia 


6.33 


1.52 


9.62 


Male... 


..28 


<» 


Endocarditis 


3.71 


2.74 


10.17 










Weight qf Iodin Per 


Total Iodin 


Sftt. 


Age, 


Cause of Death. 


Qland. 


Oram in Mg. 


in Mg. 


Male... 


..26 


years 


Liver abscess 


4.47 


2.58 


11.53 


Male... 


..46 




t 


Chronic nephritis 


5.16 


1.82 


9.41 


Male. . . 


..30 




t 


Appendicitis 


5.79 


1.98 


11.46 


Male... 


..28 




f 


Pulmonary tuberculosis 4.88 


2.28 


11.15 


Male... 


..40 




t 


Carcinoma of stomach 


3.77 


1.98 


7.46 


Male... 


..30 




i 


Multiple Endotheliomata 9.68 


1.82 


17.62 


Male... 


..35 




* 


Acute nephritis 


6.66 


1.52 


10.12 


Male... 


..41 




t 


Chronic nephritis 


6.53 


1.98 


12.83 


Female. 


..25 




tt 


Syphilitic myelitis 


5.44 


1.82 


9.9 


Male... 


..26 




t 


Pneumonia 


9.01 


1.98 


17.84 


Male... 


..66 




t 


Meningitis 


5.24 


1.52 


7.06 


Male... 


..65 


a 


Pneumonia 


4.10 


1.22 


5.0 


He also 


gives 


the following from Boston and New York : 


•Not 
5 


over 


o.c 


3 mgrs. 









66 THE THYROID AND PARATHYBOID GLANDS. 

Weight qf lodin Per Total lodin 



Sex. 


Age. 


Cause of Death. 


Gland. 


Oram in Mg. 


in Mg. 


Male... 


.30 years Phosphorous poisoning 


5.48 


2.36 


12.93 


Male... 


.45 ' 


* Suffocation 


3.65 


4.94 


18.03 


Female . 


..40 


' Pneumonia 


4.43 


1.9 


8.42 


Female . 


..25 


* Appendicitis 


3.84 


2.58 


9.13 


Male. . . 


.55 


* Pneumonia 


4.77 


1.9 


9.06 


Female. 


..40 


'* Pneumonia 


3.54 


4.56 


16.14 


Female . 


..60 


" Chronic nephritis 


3.81 


2.13 


8.12 


Male... 


.60 


Pneumonia 


3.47 


1.44 


6.86 


Female . 


.35 


' Mitral stenosis 


6.37 


2.20 


14.01 


Male... 


.47 


Poisoning 


3.44 


2.51 


8.63 


Male... 


.25 


Pneumonia 


4.65 


2.74 


12.74 


Male... 


.55 


' Meningitis 


6.18 


2.66 


16.44 



Comparing his analyses with those of Baumann and 
others he concludes that the amount of iodin is inversely 
proportioned to the amount of goitre in the district; and 
that the usually accepted theory that the iodin is de- 
creased in chronic diseases is not according to the results 
of his analyses, but that in old age the amount of iodin is 
much below the average. 

F. Blum claims that iodothyrin has an inconstant quan- 
tity of sulphur in the molecule and that the molecule is 
not saturated with iodin. He considers iodothyrin to be 
an unsaturated iodin toxalbumin, that the toxin is the iodo- 
thyrin without the iodin and that it renders harmless sub- 
stances which are being continually formed in the organ- 
ism by means of the iodin. In support of this view Roos 
shows that the saturation of the iodothyrin molecule with 
iodin renders it inert, and he finds that the artificially 
produced iodoalbumins give the same reactions as the 
thyroid albumins, and will also produce iodin compounds 
similar to but not identical with iodothyrin, which he 
claims proves that iodothyrin is a decomposition product 
from a thyroid iodoalbumin ; he also states that after the 
administration of iodid other organs besides the thyroid 
form iodoalbumins, but the thyroid the most readily. He 
concludes that the hypothetical metabolic poison combines 



CHEMISTRY OF THYROID GLAND. 67 

with the secretions of the thyroid, the most active of which 
is the one containing iodin, and that the toxin plus the 
iodoalbumin is the toxalbumin of the thyroid. 

Fraenkel extracted the dried gland with acetic acid 
when the proteids were precipitated and found the pre- 
cipitate inactive, while the filtrate was active in obesity. 
He concentrated the filtrate, treated with alcohol and 
precipitated with ether or acetone, obtaining a crystalline 
alkaloid which increased the pulse rate when injected into 
the veins of a morphinized dog from 56 to 140, and de- 
creased the convulsions but did not save the life of thy- 
roidectomized cats. 

Lanz states that thyroid sicca from swine, sheep or 
calves were equally as good, and that 10.0 grms. of fresh 
gland per day was sufficient to keep a thyroidectomized 
dog alive. Wormser was unable to keep operated dogs 
alive with any preparation except thyroid sicca. Bau- 
mann and Goldman were able to reduce the tetanic attacks 
in operated animals with from 2 to 6 grms. thyroidin per 
diem and brought the tetanic convulsions to an end with 
65.0 grms., but had to repeat the dose. Wormser found 
that the precipitate from normal salt solution with acetic 
acid did not prevent attacks or death in operated animals ; 
that the proteids with dissolved thyroidin were inactive ; 
that synthetically prepared iodin containing proteids were 
inactive. 

Hutchinson published his work on the chemistry of the 
thyroid in 1896 and arrived at nearly the same conclusions 
as Oswald. His method was to treat the fresh gland with 
a one-tenth per cent solution of sodium hydrate and to 
precipitate with acetic acid. 

E. Lepinois examined the thyroid for oxidase and found 
an indirect oxidase which gave the blue reaction with 
tincture guaiacum upon the addition of hydrogen dioxid. 
The presence of this indirect oxidase in the thyroid is of 



68 THE THYBOID AND PABATHYBOID GLANDS. 

great importance, as it may account for the increased 
oxidation in the system from the administration of the 
gland. 

Gautier claims to have found arsenic in the glands of 
dogs, swine, sheep and man. The question as to whether 
this is ingested with the food and is merely as it were an 
impurity or whether arsenic is necessary for the normal 
fimctionation of the gland has not been decided. Stein 
has found that many of the garden vegetables, such as 
cabbage, potatoes, turnips, contain arsenic. 

Paderi and Baldi have both found traces of bromin in 
the glands of dogs. If this should be confirmed and it 
should also be proved that bromin was necessary for the 
systemic metabolism, every member of the halogen group 
will have been shown to be a normal constituent of the 
body. 

Conrad and Marchetti performed complete thyroparo- 
thyroidectomy on dogs and fed them with dibromostearic 
acid. In some cases it was administered before the opera- 
tion, in one it was continued after the operation, and in 
another the feeding was entirely postoperative when the 
symptoms were at their height. This treatment appar- 
ently caused the attenuation and final disappearance of the 
symptoms for a more or less prolonged period. Not only 
was this true of the nervous and muscular excitation and 
depression but also of the cachexia, the animals living in 
a condition of apparent health. These dogs having under- 
gone the same operation, were fed with chloriodostearic 
acid and two with di-iodostearic acid. In the former 
the results were preeminently satisfactory, in the latter 
hypodermic administration only gave good results. The 
authors believe that the salutary influence of the halogens 
studied upon operated animals are to be attributed to the 
effect of the bromin and iodin, and to a more complex 
physiological action representing within certain limits 
the functioTis of the thyroparathyroid tissues. 



CHEMISTBY OF THYBOID GLAND. 69 

There seems to be no doubt that in Oswald's iodin con- 
taining thyroglobulin we have at least the chief, if not the 
only, active principle of the gland, ' and it is certain that 
iodin in the molecule is also necessary for perfect func- 
tionation. That thyroglobulin without iodin in the mole- 
cule is physiological is probable, but to what extent is not 
at present known. The phosphorus containing proteid, 
which has been classed as a nucleoproteid, though small 
in quantity, may have some physiological activity, as the 
gland has some connection with the phosphorous metabo- 
lism and the calcification of the bones. 

There are three distinct theories as to the function of 
the thyroid gland; that it is a secreting organ which is 
necessary for the metabolism or for the nourishment of 
the system ; that it secretes an antitoxin for the i)oisonous 
products of metabolism ; that there is a form of digestion 
in the gland whereby the toxic substances of metabolism 
are converted into useful and necessary substances for 
the organism by the action of an enzyme, and that in the 
absence of these necessary substances the symptoms are 
produced. 

The advocate of the latter theory is Notkin, who found 
that by the injection of 2.0 grms. per kg. of the acetic acid 
precipitate from a normal salt solution extract of the fresh 
gland into the veins or abdominal cavity of a partially 
thyroidectomized dog he produced death with symptoms 
of general paralysis, while repeated small doses produce 
a cachexia resembling myxedema. His theory is that 
there are two substances being continually produced in 
the body as a result of metabolism, one a toxin which 
produces tetanic symptoms if allowed to accumulate, the 
other is a peculiar proteid substance, which, if similarly 
allowed to accumulate, produces the cachectic condition 
known as myxedema. According to this theory it is the 
function of the thyroid to antagonize these substances. 



70 THE THYROID AND PARATHYROID GLANDS. 

The first substance is destroyed by the action of Fraenkel's 
thyroantitoxin, which is basic in nature and unites with 
and neutralizes the toxin, the convulsions in operated ani- 
mals are due to an arrest in the supply of the antitoxin. 
The second substance, which produces myxedema, is con- 
veyed to the thyroid by the blood and thus split up by a 
ferment into two constituents, one of which is of the nature 
of a carbohydrate and is set free, the other is a proteid 
which unites with an organic iodin compound, rendering 
it harmless. He denies that the iodin compound is able 
to prevent the convulsions which follow thyroidectomy, 
and he believes that it can only cure myxedema when 
there is some thyroid tissue left to utilize it, and make it 
unite with the proteid substance, which he claims produces 
myxedema. This complicated and ingenious theory has 
several objections: one is that it has been shown that the 
colloid substance without the antitoxin will prevent or 
mitigate the convulsions ; that the presence of an enzyme 
in the thyroid is purely hypothetical, there being no ex- 
perimental evidence of the existence of such a substance, 
and further, if this theory were correct thyroid feeding 
should make myxedematous patients worse instead of 
which it is curative. 

The antitoxic theory has been advocated by Ewald, 
Blum and others, being expressed in two ways, that the 
antitoxin in the gland seizes on the toxin in the blood, 
acting upon it in the gland itself, and that it is only the 
neutralized toxin which passes into the blood stream, thus 
acting in an analogous manner to the bodies of Langer- 
hans in the pancreas. The other theory is the result of 
the doctrine of autointoxication, so ably brought forward 
by Albu, by which he attempts to prove that almost all 
diseases result from this cauae; it presumes that con- 
stantly during life the normal metabolism is producing 
lower chemical forms derived from proteid, which accu- 



CHEMISTBY OF THYBOID GLAND. 71 

/ 

Ululating through failure of excretion or neutralization, 
poison the system, producing various symptoms. The 
antitoxin theory of the function of the gland presumes 
that the active principle of the gland neutralizes or de- 
composes one or more of these toxins into innocuous sub- 
stances. It is probable that the decreased oxidation re- 
sulting from thyroid insufficiency will prevent the perfect 
metabolism of the body proteids and if these imperfectly 
oxidized substances are toxic, then by increasing the 
oxidation they will be destroyed and in this sense the 
thyroid may be considered antitoxic in its functions. So 
far the advocates of this theory have failed to isolate or 
detect these toxins in the blood or in the urine of thyroid- 
ectomized animals. As previously mentioned one or two 
observers claim to have produced typical symptoms by 
injecting the serum or urine of operated dogs into healthy 
animals, but their results have not been confirmed. Ee- 
eently Basedow's disease is said to have been successfully 
treated by injecting the serum from a thyroidectomized 
goat into the patient but even if this success is confirmed 
it does not prove the theory. In opposition to the anti- 
toxic theory are arrayed nearly all the facts of experi- 
mental and chemical physiology, the extract of the gland 
reduces blood pressure, increases the amount of oxygen 
absorbed; increases the elimination of carbon dioxid, in- 
creases the nitrogen elimination by the urine and increases 
temperature in normal subjects, besides producing a va- 
riety of symptoms which are hardly compatible with the 
theory. Again, in cretinism and myxedema, two diseases 
which are admittedly due to thyroid insufficiency, the 
patients arrive at a certain stage and remain stationary, 
while if the diseases were due to the accumulation of 
toxins they would be progressive. All the metabolism 
experiments show that the action of the gland substance 
is in close relationship with the general metabolism and 



72 THE THYBOID AND PABATHYBOID GLANDS. 

it has the direct effect of increasing the assimilation of 
oxygen. How important oxygen is to the systemic func- 
tions is self-evident ; even a small excess of carbon dioxid 
in the atmosphere of a room will, by reducing the amount 
of oxygen inhaled, produce discomfort. The proper dis- 
tribution of oxygen to the various organs and tissues is 
the sine qua non of life and if this supply is decreased the 
cell nutrition and activity must be impaired. The special 
connection of the thyroid with the organs of generation 
cannot be explained by the theory that its function is 
antitoxic. 

Of the function of the parathyroids little is known at 
present; they appear to be connected with the thyroid and 
perhaps to have some special relation to the nervous 
system. 

From its origin and mode of evolution it would seem 
that the thyroid is to be considered as associated with the 
respiratory gaseous exchange of the blood and tissues, the 
phenomena following its destruction by disease or experi- 
ment are to be interpreted as a disturbance of the gaseous 
metabolism, especially with the malassimilation of oxygen 
by the body tissues, to which are probably correlated the 
subnormal temperature, twitchings, loss of fat, and the 
languor and weakness of brain and muscle tissue asso- 
ciated with the condition. It is also probable that there 
is some connection between the thyroid and the phosphor- 
ous metabolism. 



CHAPTER V. 
GOITRE. 

Goitre, struma— Goitre, French; kropf, German; gozzo, 
Italian; lobanillo, Spanish; wen, Derbyneck, English. 

The term goitre was first used by the early writers for 
the enlargement of any organ or gland which was so evi- 
dent as to be a visible deformity, but has in recent years 
been restricted to enlargement of the thyroid gland. 
Struma is an abbreviation from struere and ruma defined 
as struere rumam sen propendentem de collo mammam. 
It was also termed gutter turgidum or bronchocele. 

It is remarkable that the ancient writers on medicine 
have left so few records of so evident a deformity as 
goitre. Plinius, Vituw and Ulpian mention the disease, 
looking upon it as a divine punishment. The same view 
seems to have existed in the middle ages, as on many of 
the old churches where goitre is endemic the griffins and 
devils are represented with goitres as if it were a mark of 
depravity. Marco Polo, writing in the thirteenth century, 
mentions its existence in the highlands of Central Asia. 

Paracelsus, in the fifteenth century, describes the dis- 
ease as occurring in the Tyrol, pointing out its association 
and probable connection with cretinism. Malcarne, of 
Turin, published in 1789 a series of scientific observations 
followed in 1800 by Fodere. From this time the litera- 
ture has increased until it has become so voluminous that 
in 1893 the catalogue of the Surgeon-General's Library 
at Washington contained no less than 1857 references to 
articles on the thyroid gland and its diseases. 

Goitre occurs as an endemic, epidemic and sporadic 
disease. The endemic form occurs in more or less circum- 

73 



74 THE THYBOID AND PARATHYROID GLANDS. 

scribed areas in both hemispheres, being always associated 
with cretinism. To what extent the disease exists in 
affected districts can be gathered from the government 
military statistics. In Switzerland, between the years 
1875 and 1881, no less than 12,277 men were rejected on 
account of the deformity; in Italy, between 1859 and 
1864, 301 out of every 10,000 inhabitants were rejected, 
of whom 209 were cretins and 92 goitrous; in 1883, in 
Piedmont, there were 154 cretins for every 10,000 inhabit- 
ants; in Lombardy, 205, and in Venice 23. The total 
population of these three provinces was 9,565,000, of 
whom 12,882 were cretins and 128,730 goitrous. 

A remarkable feature of the disease is its periodicity, at 
one time declining in a particular neighborhood and then 
again increasing, or it may suddenly appear in a district 
where it was previously unknown. Denny states that 
when the French first settled at Pittsburg goitre was 
unknown, and that in 1798 it had become so prevalent that 
out of 1500 inhabitants 150 were goitrous, after 1806 it 
began to decline. 

There are many cases on record where an epidemic of 
acute goitre has occurred in places where it was previously 
unknown. In 1877, in the barracks at Belfort, Vigny and 
Eichard observed 900 cases among 5300 men. In 1889 
Angieras saw 18 cases in a wing of a pavilion among a 
regiment of infantry at Clermont-Ferrand. In Neu-Brei- 
sach in the years 1847, 1858, 1869 and 1870, an epidemic 
occurred in every fresh regiment that arrived, appearing 
as a rule in summer or autumn. Bottini observed an 
epidemic among the prisoners in Pallanga. In all cases 
these epidemics have occurred in barracks, prisons or 
seminaries, the inhabitants of the town not being affected. 
In nearly all cases these epidemics occurred in districts 
where goitre was endemic and among persons who had 
come from a nongoitrous district, who are liable to an 



GOITRE, 75 

acute attack which soon disappears after leaving the goi- 
trous district. It has also been observed that persons 
afflicted with goitre may partially or entirely lose their 
goitre on removing to a nongoitrous district. Horses, 
dogs, pigs, goats, cats and sheep have been observed to 
acquire goitre on being brought into an affected district, 
which gradually subsides after a week or a month. 

Goitre is endemic in certain districts of nearly every 
country in the world, being more especially pronounced 
in the deep river cut valleys descending from high moun- 
tain ranges where the river water has become stagnated 
and formed marshes. In Europe the valleys of the Alps, 
the Pyrenees, the Carpathians, in the Black Forest, in 
Thiiringen, in the Hartz mountains, in Sussex, Hampshire 
and Derbyshire in England it is particularly prevalent. 
The valleys of the Apennines are an exception, it being 
very rare in mid-Italy. In Kussia it occurs in Finland 
and in the Eastern provinces. In Asia it is met with in 
the valleys of the Himalayas, in Tibet and in Siberia, in 
Japan, Sumatra, Ceylon and Java. In Africa, in Moroc- 
co, Abyssinia, in the Niger valley, in the Azores and in 
Madagascar. In North America it is found in Canada, 
in the Hudson Bay territory, in Connecticut, Michigan, 
New Hampshire, Vermont and Mexico. In South Amer- 
ica in the valleys of the Cordilleras, in the central parts 
of Brazil and in Chili. Franklin observed it in Green- 
land, so that no zone is free from it. Altitude appears 
to have little effect, it having been observed in the Hima- 
layas 4000 feet above sea level. 

A disease which is so universal, and which incapacitates 
so many citizens, besides being accompanied by cretinism, 
a still more terrible affliction, has naturally been the 
subject of much scientific research. The etiology of the 
endemic goitre and cretinism has exercised the minds of 
pathologists ever since scientific observations were made 



76 THE THYBOm AND PARATHYROID GLANDS. 

upon disease. Such an evident and unsightly deformity 
and the deplorable and pitiable condition of the cretins 
has caused an immense amount of experimentation and 
theorizing. St. Leger has collected no less than forty-two 
different views on the genesis of goitre. Light, air, sea- 
son, temperature, race, configuration of the country, 
trauma, continued artificial pressure on the neck from the 
carrying of loads on the head, etc., have all had their 
advocates, but as yet no very satisfactory theory has been 
brought forward. In the Alps the natives ascribe the dis- 
ease to the drinking of snow or glacier water but as goitre 
is endemic in countries where there is no perpetual snow 
and no glaciers this cannot be the primary cause. There 
is, however, much evidence to show that it is the result of 
drinking water which rises or passes over certain geolog- 
ical strata, viz: the marine sediments of the paleolithic 
trias and tertian formations. Others again claim it is due 
to a specific organism in the waters of the affected dis- 
tricts. Virchow is of opinion that the drinking water is 
the medium through which the disease is produced and 
that the geological conditions in which the water rises or 
through which it flows are the primary cause. Kocher is 
of the same opinion. Liicke claims the disease to be of 
micro-organic origin, and that the organism only grows on 
a specific medium, entering the body with the drinking 
water. The Sardinian commission on goitre and cretin- 
ism concluded that no geological formations were entirely 
free from the disease but that it was more prevalent on 
the tertian than on the more recent strata. Bircher, after 
the most careful and painstaking research, is of opinion 
that endemic goitre is confined to definite geological forma- 
tions, viz : Devonian, Silurian, coal dyas, trias and tertian ; 
that it does not appear on volcanic or crystalline rocks, on 
the river sediments or chalk formations nor on the qua- 
ternian or fresh water sediments. 



GOITBE. 77 

Drinking water is considered by all observers to be the 
medium by which the disease enters the system, a very 
important proof of which is that certain wells in the af- 
fected districts produce the disease when their water is 
used for drinking purposes ; so well is this recognized by 
the inhabitants that it is a common practice for men to 
drink from these Kropfbrunnen so as to acquire the de- 
formity, thus escaping military service. These wells have 
been known from the earliest times, Vitravius writes 
^'Acqrieculis in Italia et Alpibus naiioni medullorun est 
genus aquce quam qui bibent effecuenter turgitis gutturi- 
bus/' It has also been observed that families or indi- 
viduals in affected districts who abstain from drinking 
from the Kropfbrunnen, using cistern water instead, re- 
main free from the disease, and even those who have 
already acquired the disease are cured or relieved by 
abstaining from the affected water. In some districts 
goitre has entirely disappeared on the inhabitants obtain- 
ing a fresh water supply. An instructive example of this 
is the case of Eupperswyl near Aarau, which changed its 
water supply in 1884, drawing it from a goitre-free dis- 
trict. The reduction in the affected children was most 
marked. In 1885 59 per cent were goitrous, in 1886 44 
per cent, in 1889 25 per cent, in 1895 11 per cent. Against 
the theory of the origin of the disease being in the drink- 
ing water is the fact that certain places drawing their 
water from the same source as a goitrous district are 
goitre free, which is possibly accounted for by the tribu- 
taries of the stream either diluting the water on its way 
to the unaffected district or by a tributary from an in- 
fected spring bringing the infection into the stream be- 
fore its arrival at the affected area. 

Many experiments have been made to produce goitre 
in animals. Bircher gave five young dogs water from a 
Kropfbrunnen for a month, as well as mixing the sediment 



78 THE THYBOID AND PABATHYKOID GLAJ^DS. 

of the well with their food but none of them developed the 
disease, which he explains by the short duration of the 
experiment and by the animals being too young, goitre not 
usually developing in the child before the fifth year. Lus- 
tig and Carle experimented with a horse and found that 
by giving the water from an infected well one lobe stead- 
ily and progressively enlarged; this they removed when 
the other lobe began to enlarge, returning to its normal 
size on giving the animal ordinary water. Thirteen dogs 
were treated in the same manner, only one developing an 
enlargement of the left lobe, and on its removal the right 
lobe began to swell, but returned to normal on filtering the 
water. Ten other dogs remained normal on being fed 
with boiled or filtered infected water. These experiments 
are not conclusive, the number of animals developing 
goitre is very small and it has been observed that animals 
in goitrous districts that show enlargement of the gland 
usually become normal in a few weeks without change of 
environment. 

From the above it seems most probable that the water 
which arises from or passes over certain geological forma- 
tions contains a *' something" which produces goitre. The 
nature of this '* something" has been investigated with the 
following results: 

Zschokke observed that the inhabitants on the right bank 
of the Aar were more subject to goitre and cretinism than 
those on the left; only this difference could be observed 
that the water on the right bank was more contaminated 
with animal and vegetable extractions than the left. 
Blondeau and Tinot analyzed the inorganic constituents 
of infected wells for lime salts, carbonates, phosphates, 
magnesia, etc., but obtained no constant results. Chatin 
in 1852 found that the water from the mountains and in 
the valleys affected contained less iodin than normal, 
which is of interest in connection with Baumann's dis- 



GOITKE. 79 

covery in 1896 that the thyroid contained iodin. Later 
investigations show so many exceptions that the absence 
of iodin cannot be considered as a cause. These analyses 
show that the inorganic salts of the drinking water have 
no connection with the disease. 

Humboldt considered that goitre and cretinism were the 
result of an infection. Vest, Bramberg, Schausberger, 
Troxler and Hirsch were of the same opinion. Virchow 
believed that the vapor contained a substance which acted 
upon the organism as a miasma. Liicke maintained that 
the miasma of goitre was similar to the marsh miasma of 
malaria. 

The bacteriological examinations of the waters of in- 
fected springs have not yet produced any definite results. 
Klebs found an infusoria which he named naviculicula, 
Bircher a diatom eucyonama, also a comma-shaped bacil- 
lus with snake-like movements, but all efforts to produce 
the disease in animals with cultures failed. Tavel ex- 
mined clear water from springs which produced the dis- 
ease and isolated thirty-three different bacteria, while in 
neighboring wells he could only find nine. Still none of 
these were apparently capable of producing the disease. 
Lustig and Carle examined twenty-five wells in the valley 
of Aosta by modern bacteriological methods. They were 
unable to find the bacillus of Bircher. They found, how- 
ever, a bacillus which was constant, liquefying gelatin, 
but which produced no effects when injected into animals 
in pure culture. 

The etiology of endemic goitre is still not proven, the 
weight of evidence points to the water which springs from 
or passes over certain geological formations being the 
means of entrance into the system of some contagium 
vivum which has as yet escaped detection. 

Occasionally in districts where goitre is endemic it may 
be congenital. Demme records 37 cases out of 642 goi- 



80 



THE THYROID AND PABATHYBOH) GLANDS. 



trous children that he examined. When congenital it may- 
be so large as to interfere with delivery, growing with ex- 
treme rapidity, causing compression of the trachea, which 
may be fatal. It is usually hyperplastic, though Demme 
has observed both the cystic and mixed forms. Its weight 
at birth may reach 10 to 20 grms., the normal being from 
2 to 5 grms. Virchow and Bednar found an enlarged thy- 
mus present in most cases ; Eulen- 
berg and Libert found persistence 
of the thymus in goitrous children 
and in adults. The persistence 
of the thymus has been observed 
in cases of Basedow's disease, and 
Ohlmacher finds it in cases of so- 
called idiopathic epilepsy with 
lymphatic constitution. 

Sporadic goitre is a totally dif- 
ferent disease from the endemic 
form, having no connection as far 
as is known with any specific in- 
fection. It is usually observed in 
young chlorotic girls who have 
developed early, and is probably 
the result of sexual disturbances, 
often suppression or partial sup- 
pression of the menses, trauma or 
hyperemia of the gland. The na- 
ture of the employment may have 
Fig. 16.— Circular stricture somc Connection with the produc- 

of the trachea from goitre, ^j^^ ^j sporadic goitre. Hahu Ob- 
(Demme.) 

ser\^ed in Luzerches that goitre 
was a common affection among the workers in needle fac- 
tories ; since this form of industry has ceased in the district 
the deformity has disappeared. There is another form of 




GOITRE. 



81 



goitre which is occasionally observed in acute diseases 
which will be described later. 

The enlargement of the gland may be unilateral, bilat- 
eral, or median, extending in various directions. In some 
cases no deformity may be visible and even its detection 
by palpation is attended with much diflSculty. In the 
median form the swelling 
extends in the direction of 
the suprasternal notch, en- 
tering the mediasternal re- 
gion. In these cases the 
gland moves with the res- 
piration and may entirely 
disappear on deep inspira- 
tion. This form is termed 
by Fodere *' goitre ende- 
dans'' or ^'goitre plon- 
geanf In other cases the 
swelling may be held fast 
by the surrounding tissues 
under the sternoclavicular 
articulation and the first 
rib, causing great pressure 
on the gland, preventing 
diagnosis by palpation. Oc- 
casionally it descends into 
the pleural cavity as far as 
the aortic arch, pressing on the lung. It may extend into 
the submaxillary region, making but little visible deform- 
ity, though reaching as far as the mastoid process. This 
is the most common direction of enlargement in children 
and in congenital cases. Another form is known as mov- 
able goitre, **Wandemden Kropf *' of AVolfler, the result 
of excessive mobility of the trachea and larynx, so that at 
one time it may be behind the sternum and at another in 
6 




Fig. 17.— Bayonet shaped tra- 
chea from bilateral goitre. 
( Demme. ) 



82 



THE THYKOID AND PARATHYBOID GLANDS. 



its normal position, differing from the ** goitre plongenat'^ 
in the regularity of the latter 's movements with the res- 
piration. 

Goitres may grow to a great size, it being not uncom- 
mon to see one the size of a small child's head hanging 
as low as the breasts. When only one lobe is enlarged 
it is usually the right, the disease as a rule commencing 




Fig. 18.— Showing the enlarged veins in goitre. (VVolfler. ) 

in this lobe, a possible reason being that the venous return 
from the right lobe is more interfered with owing to the 
relation of the vein to the heart. As the goitre increases 
in size so does the circumference of the neck, the sterno- 
hyoid, sternothyroid and sternocleidomastoid muscles be- 
ing pressed forward and outward, usually atrophying, but 
in some instances they become hypertrophied, producing 



GOITRE. 



83 



great pressure upon the gland and through it on the 
trachea, being occasionally the cause of sudden death. 

In nearly all cases of goitre the most pronounced symp- 
tom is the interference with the respiration, which may be 
caused in three ways, the prolongation of the trachea in 
relation to the larynx; nar- ^^^^ 

rowing of the lumen of the 
trachea; changes in the 
walls of the trachea; in 
severe cases all three may 
occur. Simple prolonga- 
tion of the trachea in rela- 
tion to the larynx is usually 
not accompanied with se- 
vere symptoms, but when 
accompanied by distortion 
of the trachea and conse- 
quent narrowing of the lu- 
men the respiratory symp- 
toms are much more severe. 
The contraction can be 
either unilateral, bilateral or circular, sometimes taking 
the form of the letter D, at others becoming half-moon 
shaped. In double seated compression the trachea as- 
sumes a bayonet shape. Compression of the anterior 
of the trachea is rare, being due to enlargement of the 
isthmus of the gland. After the compression has lasted 
some time trophic changes in the wall of the trachea take 
place so that the rings become soft, the trachea kinking 
as it were, sometimes causing sudden death. 

At autopsy in these cases the microscopical examination 
shows hyperemia of the mucous membrane, fatty degen- 
eration of the rings and also of the muscles of the posterior 
wall of the trachea. One of the results of the narrowing 
of the trachea is an enlargement of the lower portion of 




Fig. 19.— Bending and narrowing of 
the trachea by goitre. (Demme.) 



84 



THE THYROID AND PARATHYBOID GLANDS. 



the tube followed by chronic bronchitis. Very rarely the 
larynx is also compressed when the same degenerations 

occur. Pressure on the esophagus 
and consequent narrowing with de- 
generation of the walls may occur, 
causing difficulty in swallowing; 
complete occlusion of the esopha- 
gus has been recorded. 

The arteries and the veins of the 
gland suffer from dilatation, the 
walls becoming thin and brittle. 
The auricles dilate and dilatation 
or hypertrophy of the heart, with 
fatty degeneration of the heart 
muscle, occur in a large proportion 
of cases. 

Of the nerves the recurrent 
laryngeal, the superior laryngeal, 
the vagus, the sympathetic and the 
hypoglossus are affected in certain 
cases. 

The degenerations of the gland 
in goitre are of the nature of an 
hypertrophy with hyperplasia of 
the glandular constituents, the re- 
sult of hyperemia. The changes 
are various, resulting from the increase of the separate 
constituents of the gland, either of the parenchyma, the 
colloid substance or of the connective tissue, which may 
be classified into four forms, but which are rather a ques- 
tion of degree than of definite pathological lesions. 

Struma parenchymatose seu follicularis arises from a 
hyperplasia of the follicles, commencing by the formation 
of zones or grooves in the interstitial tissue, containing 
small empty follicles, lined with cylindrical or cubical 




Fig. 20.— Goitre of accessory 
thyroids. (Adjutolo.) 



GOITRE. 



85 



epithelium, which increase in size, forming perfect nod- 
ules containing colloid. The septa of these follicles be- 




Fio. 21.— Retrosternal goitre in a deep-seated thyroid lobe. 
(Wuhrman.) 

come thin ; the epithelium disappears, the walls give way, 
forming larger follicles of irregular shape. Zielinska 




Fig. 22. — Intrathoracic goitre. (Dittrich.) 

claims to have seen the colloid mass in the veins and ar- 
teries at this stage. The struma of the gland does not 



86 



THE THYROID AND PARATHYROID GLANDS. 



differ from normal except in the formation of blood ves- 
sels and connective tissue, the latter surrounding the 
follicles and forming a nodule while the gland remains 
soft to the touch, rarely reaching any great size. There 
is only a graduated difference between this form and the 




Fig. 23.— Follicular goitre, (v. Eiselsberg.) 



struma gelatinosa seu coUoides, the amount of colloid sub- 
stance being greater, owing to a larger number of the 
follicles and alveoli coalescing from the atrophy and pres- 
sure from the excess of colloid forming struma cystica. 
Gutkneckt differentiates another form of cyst formed by 
the breaking down of the walls of the alveoli by hyalin 
degeneration. The cysts consist of a capsule of fibrous 
connective tissue which, in the earlier stages, is lined with 
epithelium and filled with an opaque fluid containing fatty 



GOITRE. 



87 



detritus, degenerated red blood corpuscles, leucocytes, 
blood coloring matters, crystals of calcium oxalate, choles- 
terin, ammoniomagnesium phosphate, sodium and potas- 
sium chlorid, of a brown or greenish color, showing that 
hemorrhage has taken place. In old cysts there is often 
calcification, which prevents the walls from falling to- 




FiG. 24.— Goitre marked by diffuse follicular hypertrophy. 

gether when the fluid is withdrawn, broken septa often 
remain in the cyst, showing on section an apparent net- 
work through the mass, which may also contain varicose 
veins, bleeding easily. 

Struma Vasculosa.— In acute cases of hyperemic goitre 
the tumor fluctuates, pulsates, is compressible, and a mur- 
mur is audible on auscultation, while the neighboring ves- . 
sels of the neck are congested. In chronic cases there is 



88 



THE THYROID AND fARATHYEOID GLANDS. 



an equal dilatation of both arteries and veins, the latter 
being varicose. 

Struma fibrosa is produced by a hyperplasia of the in- 
terstitial tissue and is generally the result of or contem- 
poraneous with a struma follicularis. In the centre of a 
nodule there is a yellowish cartilaginous shining spot of 




Fig. 25.— Colloid goitre, (v. Bruns.) 

connective tissue. Occasionally the connective tissue is 
diffuse. The nodules are scattered through the gland tis- 
sue in circumscribed areas, it being rare for the whole 
gland to be affected. Each nodule appears like an en- 
cysted tumor with a nucleus, in which are rings of con- 
nective tissue, from which strands pass toward the centre. 
The intermediate spaces usually contain follicles. The 
nodules are poorly supplied with vessels, but sometimes 



GOITRE. 



89 



are vascular and then contain extravasations of blood 
pigment, these ultimately becoming cysts. According to 
Gutkneckt both the centre and periphery may break down 
and become calcified. 

Symptomatology.— The symptoms of goitre are very 
varied in intensity, in many cases a very large goitre may 




Fig. 26. — Follicular goitre with ectasia of the veins of the 8kin. 

cause little or no inconvenience, except for the disfigure- 
ment of the neck, while a small retropharyngeal nodule 
may produce the greatest irritation. In general, the 
goitre makes its appearance at or shortly after puberty, 
though occasionally as late even as the fortieth year, being 
more common in females than in males and may be either 
chronic or acute. The acute form is that described above 



90 



THE THYBOID AND PABATHYSOID GLANDS. 



as hypereniiaj appearing suddenly in a few hours or days. 
The tumor usually affects the whole gland, produeing 
sometimes a loud circulatoiy murmur and by pressure 
dyspnea, generally disappearing in a few days, sometimes 

returning to become chronic. 





Fm. 27,— Cyj*tic goitre. (Billroth.) 

The ehronic form makes its appearance slowly without 
attracting the attention of the patient either in one lobe or 
both, progressing slowly but surely to its maximum. At 
first no other symptoms are remarked except the deform- 
ity, with perliaj.>s passing flushings of the head and face ; 
as the gland increases in size the sjinptoras increase. In 
cases of small or medium sized goitres there is pressure 
on the veins of the neck in the neighborbood of the gland 
and on the lymphatics, producing dilatation of the veins, 



GOITEE. 



91 



cyanosis of the face, particularly' on straining or after a 
heavn^ meal, headache and a feeling of anxiet}^ As the 
tumor increases in size symptoms of pressure on the 
trachea and paraly&is of the glottis and vocal cords may 
appear, the latter caused by the pressure on the recurrent 
Jaryngeals. The pressure on tlie veins is sometimes %^ery 
great and should one of them be opened it will spurt like 




Fio. ^S.'-Cystic goitre, (v. Bnnis.) 

an artery. Should a tracheotomy become necessary the 
venous congestion ceases as soon as the breathing is re- 
stored- From the pressure of the tumor the position of 
the veins and arteries may be altered, the jugular being 
pressed toward the middle line of the neck and the carotid 
outward to a distance of 10 to 12 cm. where it may be pos- 
sible to feel it. Irregularity, increased frequency and 
palpitation of the heart are common syniptoms in youug 
chl orotic girls, probably due to irritation or jiaralysis of 



92 THE THYBOID AND PARATHYROID GLANDS. 

the vagus. Of still greater importance are respiratory 
disturbances which may come from direct pressure on the 
trachea, from nerve irritation or paralysis. The diflSculty 
of breathing increases with the growth of the tumor and 
may be greater at one time than another. When a tra- 
cheal catarrh supervenes or tke goitre is suddenly in- 
creased by hyperemia, which may occur from the exercise 
of running upstairs or walking uphill, very serious results 
are produced, requiring tracheotomy, or even death may 
supervene before the operation can be performed. There 
is also a stridor on expiration, which can be heard from a 
distance ; as the pressure on the trachea increases so does 
the stridor. In advanced cases there is also a sound on 
inspiration ; patients at this stage are compelled to inspire 
while talking quietly or to use expiration to say a word 
quickly, when there follows a long, rough whistling in- 
spiration. If a laryngeal or lung catarrh supervene a 
serious condition may arise of dyspnea or asphyxia. The 
*' goitre plongeant," or substernal tumor plays an impor- 
tant part, in some cases the tumor pressing the trachea 
between the sternum and the vertebral column. This only 
happens, however, when the tumor becomes fixed under 
the sternum. Pressure on the laryngeal nerves produces 
either an inflammatory thickening of the perineurium or 
an irritable condition of the nerve, still more often a pres- 
sure atrophy with resulting paralysis or paresis of the 
vocal cords. According to Wolfler this condition occurs 
in 10 per cent of the cases. This form has been called 
goitre asthma, producing severe symptoms of suffocation, 
through the reduction of the rima glottidis, combined with 
narrowing of the trachea. Examination with the laryn- 
goscope shows paralysis of the muscles ; in making a diag- 
nosis, neurosis, hysteria, catarrhal conditions of the air 
passages, emphysema and congestion of the venous circu- 
lation must be excluded. 



GOITBE. 93 

In the submaxillary form the posterior auricular nerve 
may be affected, causing pain behind the ear and in the 
occipital portion of the occipito-frontalis muscle. The 
sympathetic is also subject to pressure, producing hemi- 
crania and other disturbances ; probably the exophthalmos 
of Graves' disease is in part at least produced by irritation 
of the sympathetic; occasionally the spinal accessory is 
affected, producing clonic spasms of the neck. Pressure 
on the esophagus from a retropharyngeal goitre may pro- 
duce dysphasia to such an extent as to prevent the patient 
from swallowing, or a piece of food may be arrested in 
the lumen and have to be forced down with the sound. 
Wolfler found the narrowing of the esophagus in 13 per 
cent of his cases. There is a change of the physiognomy, 
which is of some diagnostic value, the head is thrown 
back, the neck stretched, the mouth widened and drawn 
backward, giving the face a stupid expression. There is 
also an intellectual weakness with mental irritability ; epi- 
leptic spasms occur, whether connected with the disease 
or merely a coincidence it is diflScult to say. 

Considering the number and importance of the various 
tissues in the neighborhood of the gland, whose functions 
may be interfered with by pressure from the tumor, the 
number of symptoms which may be produced must neces- 
sarily be very great. As the enlargement may take place 
in such a direction as to become substernal, subclavicular, 
submaxillary or retropharyngeal palpation may be diflS- 
cult or impossible. Pressure may be exerted upon the 
veins and lymphatics of the neck as well as upon the 
carotid arteries, on the pneumogastric nerve affecting the 
heart and the digestive function; upon the recurrent 
laryngeals, the superior laryngeal s and the phrenic affect- 
ing the respiration; upon the glossopharyngeal, the pos- 
terior auricular, the spinal accessory, the sympathetic and 
very rarely the brachial plexus. It may produce con- 



94 THE THYBOm AND PAKATHYBOID GLANDS. 

traction or occlusion of the trachea and esophagus, while 
an excessive secretion of the colloid material will produce 
the symptoms of thyroidismus, or, as is more often the 
case, the gland becomes cirrhotic, when the myxedema- 
tous symptoms of hypothyroidea and athyroidea will 
occur. 

The diagnosis of goitre presents no difficulties, provided 
the enlargement is in such a direction as to be visible or 
palpable. The disease has to be differentiated from 
lymphomata of the neck glands, lymphosarcoma and the 
enlarged glands of Hodgkin's disease. The swollen 
glands can be differentiated by the position and shape; 
the slow growth, the cachexia and the condition of the 
blood help the diagnosis. Should the tumor be retro- 
phaiyngeal the diagnosis may be impossible. In the ab- 
sence of the isthmus the tumor no longer follows the 
movements of the throat. Wolfler gives the following 
symptoms in these cases : Suffocation, especially at night, 
pressure on the jugular by sinking the head, a feeling of 
pressure in the aperture of the thorax, a paralysis of the 
left recurrent laryngeal nerve, one side exophthalmos, 
fixed larynx, narrowed trachea, and in some cases the 
pulse of the carotid may be different from the radial. 

For the differentiation of the different forms of goitre 
the following points are of service : 

Simple Hyperemia.— Is transient, usually connected 
with menstruation or sexual causes; the throat becomes 
round and enlarged, the larjmx is no longer prominent, 
the examiner feels only indistinctly the contour of the 
gland, which is either soft to the touch or unaltered in 
consistency. 

Struma Pare7ichymatose,—Js of soft consistency with 
sharply defined borders, the size usually about that of a 
pigeon's egg, or it may increase to that of a hen's egg, in 
the latter case it is visible ; this form is usually unilateral. 



GOITRE. 95 

Struma Vasculosa.— Does not reach any great size, is 
compressible by the finger, feeling like a sponge, a circu- 
lation murmur can be heard on auscultation. 

Struma Colloides.— Produces equal enlargement on both 
sides, the skin over the gland is tight, the jugular is di- 
lated, the symptoms are those of hyperthyroidea. 

Struma Fibrosa,— Contains hard nodules from the size 
of a pea to that of a hen's egg, with the conglomeration 
of the nodules the gland may grpw to a great size, the 
separate nodules being distinct to the touch ; in calcifica- 
tion the hardness is increased, the symptoms are those of 
myxedema. 

Mixed Goitre.— Is the largest and is usually of the 
hanging type, extending sometimes as low as the breasts. 

For the palpation of goitre it is best for an assistant to 
grip the back of the neck from behind, so that the gland 
does not slip from under the fingers of the examiner. 
Aspiration is occasionally used to determine the nature 
of the goitre, but it is not without danger. 

The course of uncomplicated goitre is slow, it may be 
from early youth to old age, though the patient usually 
seeks surgical aid either before twenty or between twenty 
and thirty. 

Besides the goitre of the true thyroid gland the acces- 
sory thyroids may become enlarged either separately or 
with the mother gland. 

Accessory thyroids are of three kinds : those which are 
not connected with the mother gland, isolated or true 
accessory glands ; those which are connected to the main 
gland by a band of connective tissue, false accessory 
glands, and those which are connected by a band of thy- 
roid tissue, connected accessory glands. They can be 
further divided according to their positions in relation to 
the main gland— anterior, posterior, superior, inferior and 
lateral— or according to the anlage from which they were 
developed. 



96 THE THYROID AND PARATHYKOID GLANDS. 

Accessory thyroids, derived from the middle or lateral 
anlages, can be either substernal, endothoracic or retro- 
clavicular, and are the most common. Occasionally the 
isthmus is lower than normal and when goitrous it lies 
under the manubrium stemi. As a rule the accessory 
gland grows downward from the isthmus analogous to the 
pyramid which grows upward. This form, when not con- 
nected with the isthmus, is sometimes called aortic struma ; 
others are connected with the inferior apex usually of the 
left lobe and are in the thoracic cavity; endothoracic 
glands, reaching to the pericardium and usually lying 
behind the trachea; others may pass behind the trachea, 
pressing upon the lungs, and are termed intrathoracic, 
while others may be grouped behind the sternum. The 
posterior accessory glands may lie behind the larynx and 
esophagus, when a goitre will contract the esophagus; 
occasionally they occur within the larynx and trachea, and 
even in the substance of the hyoid bone. The diagnosis 
of goitre of the accessory glands is attended with great 
diflSculty. 

The thyroid gland is often in an abnormal position and 
may be so low as to lie completely behind the sternum. 

The treatment of goitre is either prophylactic or me- 
dicinal, including organotherapy and surgical. 

The prophylactic treatment consists in leaving a district 
in which goitre is endemic, in abstaining from drinking 
the water or boiling it thoroughly first. If there is a dis- 
position to goitre, the patient should abstain from any ex- 
ercise which may produce hyperemia of the neck. Re- 
moval to the seacoast is often curative in the early stages. 

Of drugs iodin has been used for many years, at first 
empirically, being given as powdered sponge, which con- 
tains iodin in organic combination (spongin). Coindet, 
of Geneva, in 1820, was the first to recognize that the 
iodin was the active princii)le, and since his time the iodids 



GOITRE. 97 

have been the orthodox treatment. Kocher, who has made 
a special study of the disease, and has had an exception- 
ally large experience, is of opinion that 90 per cent of all 
goitres can be cured or improved by iodin treatment, so 
that only 10 per cent need come to the operating table. 

Iodin can be administered either by external applica- 
tion, by the mouth or by injection. 

A satisfactory method of applying iodin externally, pre- 
venting the disfigurement by staining the skin, is to apply 
a bandage soaked in from 10 to 20 per cent solution of 
potassium iodin during the night. 

Monal, Mill and Gove have used a salve containing 
about 3 per cent biniodid of mercury with good results, 
even in congenital cases. Gussenbauer recommends iodo- 
form ointment. The internal administration of iodin is 
more effective either in the form of potassium or sodium 
iodid, Lugol's solution or iodoform, but only in small 
doses, care being taken not to produce iodism. The treat- 
ment only gives satisfactory results in young people and 
at the commencement of the disease. The colloid and 
fibrous goitres are not influenced by iodin treatment. 

In 1873 the English physician, Moyen Indenland, gave 
the fresh thyroid gland of the sheep in some cases of goitre 
with good results. Emminghaus and Reinhold, having 
observed the improvement in the mental condition in cases 
of cretinism and myxedema by the administration of thy- 
roid, administered it to some goitrous insane patients. 
The mental condition of these patients was not improved 
but the goitres disappeared, v. Bruns administered thy- 
roid tablets to 350 goitrous patients and found 8 per cent 
cured, marked improvement in 36 per cent, slight im- 
provement in 30 per cent, no improvement in 26 per cent. 
The treatment produced the best results in young patients 
with follicular hypertrophy. In struma fibrosa the nodes 
were not reduced in size, but the intermediate tissue was 
7 



98 THE THYKOID AND PABATHYROID GLANDS. 

absorbed, reducing the size of the goitre, rendering opera- 
tion unnecessary. 

V. Bruns studied the action of the thyroid treatment on 
twelve goitrous dogs by removing a portion of the gland 
before and after treatment and found that the effect of the 
feeding was to increase the amount of colloid in the tissue 
of the struma, it being apparently greater than in the nor- 
mal gland, the lymphatics being gorged with colloid, the 
undeveloped tissue was absorbed, the vessels partially ob- 
literated. The total result he described as a trophoneu- 
rotic atrophy of the gland. Kocher excised a colloid 
goitre after several weeks' treatment with thyroid and 
found that only a portion of the alveoli contained colloid, 
and those that did contain colloid were only from a third 
to a quarter full. He came to the conclusion that there 
was no difference between the action of the thyroid and 
iodin. Kijewski saw symptoms of Basedow's disease dur- 
ing treatment. K. Serapin found that colloid, cystic and 
vascular goitre were not benefited, but that the fibrous 
goitres became somewhat softer and smaller. 

V. Mikulicz claims to have good results from the admin- 
istration of thymus. 

The direct injection of tincture of iodin or iodoformol 
into the gland was first introduced by Skoldberg in 1855, 
and later by Luton in Rheims and Liicke in Strassburg. 

Pring investigated the effect of the injection of iodin 
into the glands of animals. He found that two or three 
days after the injection of 0.2 ccm. of tincture of iodin 
there was a serofibrous exudation at the point of punc- 
ture with necrosis of the cells of the parenchyma, which 
necrosis did not take place if salt solution were used in- 
stead of the iodin. After one or two weeks there was a 
formation of connective tissue. After the injection of 
alcohol there were the same results, but to a less degree. 
After the injection of iodoform there was parenchymatous 



GOITBE. 99 

coagulation necrosis without fatty degeneration of the 
cells. The colloid substance was not absorbed as a result 
of the injection. The injection is not without danger, as 
sudden death may occur if the injection is made into one 
of the larger vessels. Another danger is that the injection 
may go into the trachea. The operation must be per- 
formed imder strict antiseptic precautions. The danger 
of injection into a vessel can be guarded against by with- 
drawing the canula and observing if it is followed by 
blood; if so, another place must be chosen for injection. 
To be sure that the needle is in the goitre it is necessary 
to notice if it moves when the patient swallows. 

The injections are usually given twice a week, the first 
injection should not contain more than 0.25 to 0.5 grms. 
tincture of iodin, gradually increasing to 1.0 grm. of the 
tincture or 3.0 grms. iodoform solution. 

The action of this treatment is Usually very slow, it be- 
ing often three or four weeks before any improvement can 
be noticed. The results are satisfactory in a large per- 
centage of cases in struma foUicularis, but is of no value 
in struma fibrosa. Gaire treated 140 cases, in 90 per cent 
all symptoms of trachea stenosis disappeared. He used a 
solution of iodin 1.0 grm.; ether, 7.0 ccm. ; olive oil, 7.0, 
which must be kept in dark-colored bottles and carefully 
stoppered. Alcohol injections have been recommended 
by Schwalbe. Ergotin, strychnin, osmic acid, Fowler's 
solution, 1 per cent carbolic spirits, carbolic acid, papain, 
permanganate of potash, ferric chlorid, chromic acid have 
been tried but with unsatisfactory results. 



CHAPTER VL 
SURGERY OF THE THYROID GLAND. 

When medical treatment has failed surgical interfer- 
ence may become necessary under special circumstances. 
If the dyspnea is so constant as to incapacitate the patient 
for following active employment, or one of a sedentary 
kind especially, such as involves the bending of the neck 
so that the patient is prevented from earning a living, and 
if the disease is progressive an operation should be ad- 
vised. Should there be tracheal stridor accompanied by 
a goitrous isthmus or extension of the swelling laterally 
or downward, there are often sudden attacks of dyspnea, 
which may end fatally before assistance can be given. 
These sudden attacks of dyspnea are due to some extra 
exertion which calls into action the additional muscles of 
respiration, the sternocleidomastoid, the sternohyoid and 
the sternothyroid, which, pressing on the goitre, produce 
still further narrowing of the trachea, thereby increasing 
the dyspnea, and as the dyspnea increases the action of 
the muscles becomes still further increased, producing 
closure of the trachea and death. Another cause of sud- 
den enlargement, increasing the dyspnea, may be sudden 
extravasations of blood into the goitre. 

In emergency it is best to slit the deep cervical fascia 
and to raise the muscles that press upon the gland, allow- 
ing it to bulge forward away from the trachea; at the same 
time should there be cyanosis venesection should be re- 
sorted to. If the foregoing do not give relief either the 
gland or isthmus or both must be partially removed, or 
tracheotomy performed, if the patient's condition will ad- 
mit of the operation. Tracheotomy is often very diflScult 

100 



SURGERY OF THE THYROID GLAND. 101 

under these conditions. Should the enlarged isthmus 
permit of the operation above the gland there is usually 
no convenient canula at hand, a large rubber catheter may 
be used or a Durham's canula with a rubber attachment; 
should there be substernal enlargement Konig's catheter 
should be substituted as soon as possible. Opening the 
trachea below the isthmus is often impossible when the 
gland is much swollen, reaching as it often does from the 
cricoid cartilage to the manubrium. To divide the isth- 
mus and then perform tracheotomy is attended with great 
danger of hemorrhage followed by septic pneumonia. 
The dangers of low tracheotomy consist in the number of 
large vessels, such as the innominate artery, which may be 
accidentally cut, as well as of injury in the confined area 
to the dilated vessels of the gland itself, while the danger 
of pneumonia is increased. Should the goitre be uni- 
lateral it is probably due to adenoma or cyst ; in the latter 
case it may be drained or removed, in the former the 
tumor should be enucleated if possible, if not the lobe 
must be removed. Removal of the isthmus may not re- 
lieve the symptoms. Should this be the case one lateral 
lobe should be entirely removed. It is probably better 
should the condition of the patient permit to remove the 
isthmus and one lateral lobe at once rather than resort to 
tracheotomy, as the latter invariably causes a septic 
wound and very often produces pneumonia. 

Another indication for operation is the steady enlarge- 
ment of the gland, with or without dyspnea, especially if 
the enlargement is in the downward direction where it 
will become substernal. The lower the growth extends 
the greater is the danger of mediastinal cellulitis after 
operation and the less chance of giving relief by tracheot- 
omy in emergency cases. Another symptom which indi- 
cates operative treatment is the inability to stoop without 
a sensation of blood to the head; the inability to sleep 



102 THE THYBOID AND PAKATHYROID GLANDS. 

lying down so often associated with asthma, is also a 
serious symptom. In the first instance the feeling of rush 
of blood to the head must be due to pressure on the gland, 
which in its turn presses on the jugulars, and in the second 
the weight of the gland pressing upon the larjmgeal 
nerves may be the cause of the asthma and discomfort. 
When the tumor is very large there is often a dragging 
pain at the neck, sometimes without any other symptom. 
The questions which the surgeon has to consider are the 
probabilities of a sudden and perhaps fatal attack of 
dyspnea, and if the tumor is progressive, in both cases he 
is justified in advising operation after fully weighing the 
dangers of the operation, which are increased under the 
following conditions: 

If the goitre is very large, and especially if it is fi^ced on 
a broad base, if the goitre is calcified, or if its limits are 
indistinctly defined, the risks of operation are materially 
increased. In those cases which are substernal the risk of 
mediastemial cellulitis is great. The age of the patient is 
also of moment, Billroth being of opinion that no opera- 
tion should be i)erformed after the age of forty unless 
there is malignant disease, and as malignant disease only 
attacks unhealthy glands he would operate early. On no 
account should the operation be performed for the sake 
of the personal appearance only above this age, but in 
early adolescence when the gland is not very large, it is 
permissible for fear of future dyspneic symptoms or 
malignant growth. Patients with feeble pulse, which is 
the result of pressure on the veins and trachea and from 
the intervention of a more or less voluminous vascular net- 
work producing strain on the heart, are apt to succumb to 
the operation. 

There are a number of cases which appear to be allied 
to Basedow 's disease but which have not the typical symp- 
toms and are to be operated upon with caution, there being 



ttUBGEBY OF THE THYBOID GLAND. 103 

greater risk of excessive action of the heart, pyrexia, and 
perhaps lung trouble. These cases are usually young pa- 
tients with a soft parenchymatous goitre affecting the 
whole gland, with marked vascxilarity, pulsation, a pulse 
of 90 or more, the heart easily excited, with a soft systolic 
bruit. These are cases which are suffering from hyper- 
thyroidea, and are distinct from other forms of goitre. 
After the operation the patient is restless and depressed, 
there is a constant effort to clear the throat by coughing, 
which disturbs the wound ; he feels a dread of suffocation 
from the accumulation of mucus in the trachea and larger 
bronchial tubes ; the pulse runs up to 120 or 130, the tem- 
perature rises, which is followed by exhaustion and death. 
Should the patient survive the wound does not heal by 
primary union, there is a profuse blood-stained discharge 
for several days, though it may not be infected. These 
symptoms are not uncommon after operation for Base- 
dow's disease and are probably the result of a quantity of 
colloid substance having been expressed out of the gland 
during the operative manipulations. Great care must be 
exercised in handling the gland so as to prevent pressure 
causing the exudation of the colloid substance, and the 
wound washed out with sterilized water. It is well to 
place some absorbent cotton in the wound, renewing it 
every two or three hours so as to prevent any further 
exudation from entering the system. If this is attended 
to the symptoms, which are those of thyroidismus, will 
disappear. 

In case of partial extirpation or enucleation the wound 
usually heals well and the respiratory symptoms are re- 
lieved, the constricted trachea returning to normal in a 
short time. Should there have been paresis of the laryn- 
geal nerves from pressure of the goitre and consequent 
failure of the voice there will usually be a return to normal. 
Kronlein found that out of 25 cases of inhibition of the 
vocal cords 21 returned to normal after the operation. 



I 



104 . THE THYROID AND PARATHYROID GLANDS. 

The operation for the removal of goitre was for a long 
time considered, and not without reason, as being one of 
the most dangerous attempted, but, thanks to antisepsis 
and asepsis, special technique and the recognition of the 
cause of tetany and cachexia strumipriva, which at first 
so often followed the operation, the mortality in the hands 
of good operators has fallen to almost nil. Billroth, of 
Vienna, and Kocher, of Berne, have been the two surgeons 
to whom is due this most satisfactory result. Kocher had 
no mortality in 272 consecutive cases, Kronlein in 200, 
Roux in 526 operations had a mortality of 1.27 per cent; 
v. Mikulicz in 151 2.6 per cent; v. Bruns a mortality of 
2.0 per cent. Riverdin collected the statistics and found 
that in 6103 operations the mortality was 2.88 per cent. 
Riverdin also gives the statistics of 93 cases of death from 
the operation, 42 being from suffocation, asphyxia or pneu- 
monia, 19 from hemorrhage, 13 from wound infection, 9 
from shock and wounding of the recurrent laryngeals, 6 
from heart syncope and 4 from tetany or myxedema. 

The most dangerous complication during operation is 
hemorrhage, which can be guarded against by a sufficiently 
large incision, adequate retraction or division of the over- 
lying muscles, and by identifying the capsule. The latter 
is often difficult, the layers of the deep cervical fascia over 
the tumor vary in thickness and number, each one must be 
divided carefully till the tumor is reached, which can be 
recognized by its purple red color, its consistency and the 
way the vessels stand out and ramify over the surface. 
The arteries are usually easy to manage but the veins give 
great trouble, being very numerous, thin-walled and are 
met at every step of the operation. When the growth is 
soft as well as vascular any opening of the capsule is apt 
to flood the wound with blood, making it difficult to find 
the bleeding point, increasing the danger of including the 
nerves within the ligature. Asphyxia and aphonia may 



SURGERY OF THE THYROID GLAND. • 105 

occur from including a recurrent laryngeal nerve within a 
ligature, cutting the nerve or bruising it. Aphonia may 
be the result of wounding the inferior laryngeal or drag- 
ging on it ; possibly section of the cricothyroid branch of 
the superior laryngeal nerve may also produce aphonia. 
Months after the operation these symptoms may appear, 
owing to inclusion of the inferior laryngeal nerves in the 
cicatrix. There is also a progressive ascending neuritis 
of these nerves which may have commenced anterior to 
the operation, due to compression of the goitre. When 
the growth is large or when fixed by adhesions or attached 
by a broad base the nerves are apt to be injured ; also when 
the tumor is ill-defined or encircles the trachea and eso- 
phagus closely, as it usually does when the disease is 
malignant. 

Even after every care postoperative hemorrhage is not 
uncommon so that it is requisite that the patient be care- 
fully watched, any change of color or weakness of pulse 
calling for immediate examination. The venous hemor- 
rhage is possibly even more dangerous than the arterial, 
owing to the possible formation of air emboli, which may 
cause sudden death, the veins in the neighborhood of the 
operation being without valves and the vessels dilated. 
Treves recommends washing with normal salt solution and 
leaving it in the wound, so that it will be aspirated into 
the jugular instead of air. Should the recurrent laryngeal 
nerves be accidentally cut during the operation paralysis 
of the vocal cords will follow. Wounding of the superior 
laryngeal nerves and of the sympathetic has to be guarded 
against. In the first case anesthesia of the lining mem- 
brane of the larynx will ensue. Wounding of the sympa- 
thetic produces postoperative ptosis, one-sided wideninc^ 
of the pupil and sinking of the eyeball. In a case in Bill- 
roth's clinic there was narrowing of the pupil, a differ- 
ence of temperature between the right and left side of the 



106 THE THYBOID AND PARATHYBOID GLANDS. 

face, congestion and heat on the operated side, combined 
with heavy sweating and increased secretion of the saliva. 
Should the hypoglossal nerve be injured paralysis and 
atrophy of one half of the tongue will occur. 

The most dangerous of the postoperative complications 
is infection of the wound, which may result from faulty 
technique; from the vomiting of the patient into the 
wound, or from wounding of the esophagus. Should it 
have been necessary to perform tracheotomy the proba- 
bilities of infection are very great. In many cases death 
follows rapidly on infection, which may extend into the 
mediastinum, causing dyspnea, severe pain under the 
manubrium stemi, pain on pressure, sweating and high 
fever. The wound must be at once thoroughly opened 
and cleaned. Hyperthermia to about 38 degrees C. is 
common in thyroid operations. Bergeat observed it on all 
but three out of 249 operations, other surgeons observ^ed 
it in from 60 to 80 per cent of their cases. It seems prob- 
able that this hyperthermia is the result of the gland being 
squeezed during the operation, causing exudation of col- 
loid and is really the result of hyperthyroidea. Some- 
times there is very difficult breathing after the operation, 
which may be due to too tight bandaging, too much tam- 
pon in the wound, to postoperative hemorrhage, which, 
by producing a large hematoma, may press on the trachea 
or, in cases of tracheotomy, bleeding into the trachea. In 
other cases there is an accumulation of mucus, which re- 
quires that the pharynx be washed out with the head 
hanging downward; this complication predisposes to 
pneumonia. Occasionally the trachea may kink through 
some sudden movement of the head. 

A complication which is to be dreaded is pneumonia, 
which may develop very quickly, when it is probably 
caused by venous sepsis. As a rule, however, it develops 
slowly during the first few days after operation; paralysis 



SURGERY OF THE THYROID GLAND. 107 

of the larynx through injury of the recurrent laryngeal 
nerves is a predisposing cause, as during sleep the glottis 
is open, the saliva and mucus from the mouth flows into 
the trachea. Wolfler injected human saliva into the 
trachea of rabbits, but failed to produce pneumonia; on 
the other hand, if infected substances were injected lob- 
ular pneumonia followed. Difficulty and pain on swal- 
lowing is usual for the first few days after operation, when 
it gradually disappears. 

The administration of an anesthetic is a point which re- 
quires much discretion and is still debatable. The danger 
of excitement at the commencement of anesthesia increas- 
ing the respiratory disturbance causing risk of as- 
phyxia has to be borne in mind ; often the condition of the 
lungs from chronic catarrh or emphysema, as well as dila- 
tation of the right heart, cause the surgeon the greatest 
anxiety. The venous stasis, already severe, will be in- 
creased, while vomiting may cause sudden death. Many 
operators use no anesthetic, on the ground that the hand- 
ling of the goitre is almost painless, the pain being only at 
the first incision and the luxation of the tumor; others 
use cocain, Schleich infiltration or other methods of local 
anesthesia. In some few emergency cases patients are 
brought to the table in a semiasphyxiated condition, when 
the danger of anesthesia is so great that the surgeon will 
be compelled to operate either with local anesthesia or 
with none, but these are few and far between. In any case 
the patient must be placed in the position in which the 
difficulty of breathing is least, which the patient is usually 
able to explain, and may be either sitting or extended; 
the head should be firmly fixed so as to prevent any sudden 
motion. A bolster is placed under the neck and the hands 
held by an assistant. Every care must be taken not to 
excite the patient. There should be a protector placed be- 
tween the face and the field of operation to prevent infce- 



108 THE THYBOID AND PARATHYROID GLANDS. 

tion from the saliva or from the patient vomiting into the 
wound. 

The parts having been prepared, the head and shoulders 
conveniently supported and secured against movement, 
a free incision is made along the anterior border of the 
sternocleidomastoid over the most prominent i)ortion of 
the tumor, avoiding large veins. An ample longitudinal 
incision will usually be suflScient and leave little noticeable 
disfigurement, as the scar will fall into the sulcus internal 
to the muscle. It is rarely necessary to make more than 
the longitudinal incision. The skin and platysma are cut, 
the superficial veins tied, the deep fascia divided, and the 
hyoid depressors separated or divided. If necessary the 
patient will usually begin to breathe more easily. It is of 
importance that the opening, both in the skin and in the 
fascia, should be ample, giving plenty of room to prevent 
the squeezing of the gland, which may cause the serious 
consequences mentioned above. The goitre on being laid 
bare can be recognized by its blue red color and large 
veins, which stand out as they ramify over the surface of 
the gland. 

The sternomastoid is retracted, drawing out the large 
vessels, then with his finger or blunt scissors the surgeon 
frees the tumor from its bed, shelling it forward, probably 
finding that it is only fixed above, below and internally. 
Care must be taken to work gently and to keep close to 
the tumor. As the veins are distended and the walls thin 
great care must be exercised not to injure them, and on 
no account must the capsule be broken. Should this occur 
the wound is at once flooded with blood. The upper ex- 
tremity is freed first, the superior vessels ligated, either 
doubly with chromic gut passed with an aneurysm needle 
or divided between two pairs of forceps, both ends being 
tied. The tumor must be isolated in a downward direc- 
tion and any portions which may exist under the sterno- 



SURGERY OF THE THYROID GLAND. 109 

mastoid muscle turned out. It is better to now divide the 
isthmus, which can be done either by double ligature after 
transfixing with an aneurysm needle carrying strong gut 
or it may be torn through and each bleeding point tied. 
If it should be very vascular and large it should be subdi- 
vided and tied in several places, the ligatures interlock- 
ing; it may be seared through with the cautery or by an 
ecraseur, the stump should then be treated with zinc 
chlorid or formalin, packed with sterilized gauze and 
brought outside the wound. The tumor is now drawn to 
one side and the inferior vessels dissected out; as the re- 
current laryngeal nerve runs along with the inferior thy- 
roid artery when near the gland the artery should be 
ligatured as near the axis as possible always examining 
carefully to be sure that the nerve is not included in the 
ligature. After the gland is removed all bleeding points 
must be stopped and the wound thoroughly dried out. 

The wound even after removal of one lobe only is often 
very large and deep, the larynx, trachea, esophagus and 
large vessels all being exposed, as well as the dome of the 
pleura, and is difficult to drain properly, as it dips below 
the clavicle. In parachymatous cases, where the opera- 
tion has been easy and the parts little disturbed, the sur- 
geon will dispense with draining and trust to a dry wound 
and carefully applied pressure. The edges should be 
exactly brought into position to promote easy healing. 
The scar may become keloid, but this is only temporary, a 
white scar being the only disfigurement. The dressing in 
immediate contact with the wound should press evenly, 
distributing the discharge over a large surface of dress- 
ings and obliterating the cavity. In order to keep the 
dressings in position the bandage should be passed under 
the axillae, using a pad, and then wound round the chin and 
forehead and made secure with stitching; this prevents 
the bandage slipping and exposing the upper half of the 



110 



THE THYROID AND PABATHYBOID GLANDS. 



wound. Under the chin should be a protector to prevent 
the dressings being soiled by the saliva, etc. Should, 
however, the parts be much disturbed during the opera- 
tion drainage is advisable. In cases where there may be 
exudation of thyroid secretion the sutures may be left long 
and untied, the wound plugged with sterilized gauze, and 
after a few days the gauze may be removed and the su- 
tures tightened. 

Tracheotomy should never be performed except in most 
urgent cases, as the results are almost always fatal from 
septic infection of the wound, septic bronchopneumonia 
and partly from increased shock. If apparently needed 
the surgeon should first divide the fascia and muscles and 
endeavor to ease the pressure by letting the tumor bulge 
forward. The tracheotomy wound requires great care 
and attention; the wound must be left open and washed 
with bichlorid 1 to 4000 very frequently, but in spite of all 
precautions septic infection will ensue. 




-Struma Vasculosa 



Fig. 30.— Adenoma of Thyroid. 



Enucleation of thyroid adenomata has been advocated 
by Porta, Billroth, Socin, Riverdin, Wolfler, on the ground 
that there is less danger of wounding the nerves and hem- 
orrhage, and also that there is certain to be enough active 
thyroid tissue left to prevent tetany or cachexia strumi- 



SUBGEBY OF THE THYBOID GLAND. Ill 

priva. As early as 1804 Briininghausen enucleated a 
cyst; in 1884 Billroth had performed 8 operations suc- 
cessfully. 

In ordinary cases of solid enlargement of the thyroid 
encapsulated adenomata are often present, which can be 
comparatively easily enucleated, and is a much less severe 
operation than the partial removal of the gland. The 
incision is the same as in the partial removal, the fascia 
being divided in the same way. On the gland being ex- 
posed it is necessary to examine and palpate carefully in 
order to define accurately the limitations of the capsule of 
the adenoma. Usually it is easily recognized, rarely the 
side of the gland will have to be raised and explored. The 
adenomata can be recognized by its smooth white cover- 
ing. Adenomata may be multiple, in which case each 
must be enucleated separately, or those left behind will 
continue to grow and necessitate a second operation. 
After enucleation the gland does not shrink so completely 
or permanently as after the extirpation of one lobe and 
half the isthmus. The operation of enucleation is not 
applicable to the gelatinous form and should never be 
tried unless the adenoma can be distinctly defined. It is 
rare that cysts or adenomata occur in bilateral goitres, 
they being usually unilateral. Patients suffering from 
unilateral goitres rarely seek operation, as the dyspnea is 
not severe. On the whole partial removal of the gland is 
preferable, giving better results and less probability of a 
return. 

Removal of the isthmus alone is often followed by 
shrinkage of the tumor and has the advantage of requiring 
less preparation, enabling the surgeon to give relief in 
emergency cases, when the slitting of the skin, muscles 
and fascia has failed to give relief without much assist- 
ance. It is preferable in cases of very large growth, 
when anesthesia is dangerous and time is short, or when 



112 THE THYROID AND PARATHYBOID GLANDS. 

the enlargement of the isthmus is the cause of the tracheal 
stridor. 

In cases of malignant disease the dangers of the opera- 
tion are much increased, as the growth hugs the trachea, 
dipping into the sulci between the large vessels and the 
trachea, infiltrating imi)ortant parts, often growing into 
the mediastinum. Under these conditions the probabili- 
ties of wounding the nerves and vessels are very much 
increased. 

Another form of operation, which has recently been 
advocated and practiced with success, is ligature of the 
arteries of the gland, leaving the tumor in situ. This 
operation has given contradictory results, splendid results 
being opposed by utter failures. The failures are due to 
the existence of abnormal arteries, as if all arteries are 
tied the circulation must cease, and the gland atrophy, 
but if the circulation is not cut off or reestablishes itself 
the operation will fail. Experience has shown that liga- 
ture of all the arteries does not produce gangrene. 

The difficulties of the operation consist in the finding 
of the arteries, they varying much in position, in that the 
vessels are often diseased and in that the nerves are apt 
to be ligated with the vessels. The landmarks for the 
arteries are as follows: 

The superior thyroid, the first branch of the external 
carotid, arises just above the bifurcation of the common 
carotid about one-quarter of an inch below the great cornu 
of the hyoid bone, covered at first only by thin fascia and 
the platysma, it ascends slightly and then curves down- 
ward, taking a tortuous course covered by the depressors 
of the hyoid bone and the sternothj^roid. 

The head should be raised and turned to the opposite 
side; the incision is made along the inner border of the 
sternomastoid muscle, with its centre corresponding to 
the upper border of the thyroid cartilage, the stemomas- 



SURGERY OF THE THYROID GLAND. 113 

toid and large vessels are drawn outward and the omo- 
hyoid downward and inward, and the artery sought for in 
the hollow between the larynx and the carotid. Usually 
there are also present some enlarged veins of superior 
thyroid which will also require ligatures. 

The inferior thyroid is more difficult to find. It is the 
largest branch from the thyroid axis of the subclavian, 
ascending tortuously inward behind the carotid sheath, 
the middle cervical ganglion lying in front of it. Before 
entering the gland it runs a short distance in close relation 
with its posterior surface, and the recurrent laryngeal is 
then in contact with it, often passing between the terminal 
branches of the artery ; further, the left artery is often in 
close contact with the esophagus, while the thoracic duct, 
at first posterior, arches over the artery on this side to 
enter the subclavian vein. The tubercle of Chassaignac 
or the transverse process of the sixth cervical vertebra and 
the body of the fifth vertebra are landmarks for the point 
at which the artery enters the gland. 

The incision is made along the anterior border of the 
sternocleidomastoid to the clavicle, as if to ligate the caro- 
tid low down, the fascia divided, the sternomastoid and 
the carotid sheath and contents drawn out. The head is 
then flexed to relax the carotid, the tubercle felt for and 
the artery sought for below, working with a director, the 
vessel exposed and then ligated. Great care has to be 
exercised as the artery is often degenerated and friable 
from pressure, and in order to avoid the nerve it is as 
well to ligate as close to the carotid as possible. The 
presence of the phrenic nerve has also to be borne m mind. 

This operation seems especially useful in Basedow's 
disease. 

Cysts of the gland, though usually only unilateral, may 
grow to a great size and require removal. Occasionally 
the injection of ferric chlorid gives good results, but there 
8 



114 THE THYROID AND PARATHYBOH) GLANDS. 

is a risk of suppuration and cellulitis. Should the cyst 
not be of any very great size it may be excised, it turns 
out easily if it has not been previously blistered, when 
adhesions usually exist. 

If convenient it may be emptied first and then, by 
squeezing the edges, turned out empty. After such an 
operation the lobe appears to be useless, but should on 
no account be removed but bandaged in such a way as to 
apply even but not excessive pressure. Should the cysts 
be multiple the whole lobe must be removed. 

If excision is impossible incision must be practiced. 

Clean up the operating field and cut down as previously 
described, carefully securing all bleeding points, slit open 
the cyst and examine. The contents may be either gelat- 
inous or grumous, serous, mucoid or coagulable blood 
clot. On examination the wall of the cyst, if of long 
standing, may be so fibrous and evascular that sloughing 
may take place; on the other hand, it may be vascular. 
Should any of the vessels be wounded very suddenly, 
leaving no time for suturing, it will be necessary to plug 
at once. These cysts are difficult to heal from the bottom, 
the edge of the slit may be sewed to the skin, the inside 
curetted and packed lightly. 

In all these operations there is very considerable risk 
from hemorrhage, from infection, from exudation of the 
colloid substance from the gland, from injury to the 
nerves and vessels, as well as the danger of asphyxia 
during anesthesia. As shown above the mortality from 
the operations is not large. Riverdin collected the mor- 
tality .of the various operations, which are : 

Percent 
Mortality. 

Intraglandiilar enucleation 0.78 

Combined enuclear resection 2.99 

Partial extirpation 3.46 

Resection according to v. Mikulicz 6.66 



SUBQEBY OF THE THYROID GLAND. 115 

There are two diseases which occasionally follow the 
complete excision of the thyroid gland, or if a sufficient 
quantity of active gland substance is not left in situ. 

As early as 1818 Ch. Jong and in 1833 Langenbeck ob- 
served spasms occur after the total excision of the thyroid 
gland; in Billrot's clinic between 1870 and 1880 the dis- 
ease was observed about forty times after operation. 

The disease exhibits itself in tetanic spasms, somewhat 
resembling tetanus, which occur not only in the extremi- 
ties, but also in the muscles of the larynx and diaphragm, 
soon causing death. The convulsions are of two grades 
of intensity, which may occur in the same case, the lighter 
ones occurring in the early stages, increasing in severity 
as the disease nears its termination. Sometimes the con- 
vulsions appear immediately after the operation, at others 
not till ten days later. Usually there are premonitory 
symptoms of an attack, consisting of a feeling of uneasi- 
ness and stiffness, with a weakness in the muscles of the 
forearms and the calves of the legs; rarely there are no 
premonitory symptoms, the attack coming on with great 
suddenness. In many cases it is possible to predict a 
tetanic condition before the first spasm, from the feeling 
of numbness, etc., and more especially from the Chvostek 
and Trousseau phenomena. The first consists in very 
rapid sucking movements, which are produced by light 
taps on the facial nerve as it leaves the parotid gland. 
The second and by far the most important of the two is 
that in a few minutes after pressure on an artery or nerve 
a convulsion of the part which they supply is produced. 
Chvostek *s sign is so easily carried out, being without any 
danger or discomfort to the patient, that it should be 
always tried after total extirpation of the gland. Trous- 
seau's sign is not without danger, as the muscle convul- 
sions which it produces may be very severe. The convul- 
sions usually begin in the calves of the legs and with a 



116 



THE THYROID AND PARATHYROH) GLANDS. 



feeling of numbness in the face ; in light spasms the con- 
vulsions are usually confined to the upper extremities, 
seldom occurring in the lower extremities at the same 
time; the position of the joints of the hand and fingers 
suggest irritation of the ulnar nerve, the arm is slightly 
bent at the elbow and flexed toward the ulnar side, the 




Fig. 31.— Cachexia strumipriva in a girl 2G years old. (v. Briins.) 

fingers bent at the metacarpophalangeal joint, the inter- 
phalangeal joint is straight and the thumb in the palm of 
the hand, as in the typical writer's or mid-wife's hand. 
This is the most common position; in other cases the 
fingers are extended wide apart or the fist is closed, with 
the thumbs between the index and middle finger. The 
muscles of the forearm are hard and tense to the touch; 
it is difficult to move the joints of the hand or fingers 



SUEGEEY OF THE THYEOID GLAND. 117 

during the spasm; they immediately return to their for- 
mer position. In the majority of cases the spasms of the 
upper extremity are accompanied by the lower, which con- 
sist of stretching of the hip and knee with plantar flexion, 
the tendons drawn to the sole of the foot, while the severest 
strain is on the calves. The expression of the face shows 
intense pain, there is profuse sweating, the temperature 
may rise a little, the pulse rate be increased. The spasms 
last from two or three minutes to a quarter of an hour or 
more and occur several times in the day or one each day, 
or on alternate days. The sensorium is always free. 
Sometimes there is edematous swelling of the extremities. 

The severer forms, which usually begin with a light 
spasm and slowly or rapidly progress in intensity, may 
last in spite of medication for days with hardly any ap- 
preciable break. In these cases there is also contraction 
of the muscles of the face, they become fixed, the mouth 
resembling that of a fish. The abdominal muscles are 
also severely contracted, the recti standing out like strands 
of steel. The tonic spasms of the back often produce opis- 
thotonos. When the spasms attack the diaphragm the 
respiration comes to a standstill, in expiration followed by 
severe dyspnea. The contraction of the muscles of the 
neck produces cyanosis. The patients suffer from great 
pain as well as from air hunger, sometimes shrieking, in 
other cases this is impossible, owing to spasm of the mus- 
cles of the larynx, articulation may be possible at short 
quick intervals, when the same word may be repeated each 
time. Swallowing is also impossible, so that only small 
quantities of fluid can be given. As the end approaches 
the patient becomes comatose and the spasms cease, only 
to commence again when he is aroused from the coma. 
Death rarely supervenes during the height of the spasms, 
but hours or days after they have subsided. 

The microscopical findings are negative, twice Weis 



318 THE THYBOID AND PAKATHYBOID GLANDS. 

found slight infiltration of the gray matter of the anterior 
horn of the medulla. 

From the experiments on the extirpation of the thyroid 
and parathyroid glands recorded above, it is probable that 
the tetanic convulsions after total excision of the gland 
are due to the parathyroids having been included in the 
tissue excised, especially as cases of tetany have occurred 
where there was apparently sufficient active thyroid tissue 
left in situ to prevent the patient suffering from athy- 
roidea; in the latter case the parathyroids have either 
been injured before or during the operation or have been 
completely removed. It is probable that operative tetanic 
thyropriva will be very rarely seen in the future, surgeons 
being fully alive to the importance not only of leaving 
sufficient thyroid substance but also the parathyroids. 
Should a case occur the treatment consists in thyroid and 
parathyroid feeding, but the prognosis is very unfavor- 
able. 

Cachexia strumipriva is really a myxedema produced 
by the removal of the thyroid gland, either totally or par- 
tially, by operation. In 1867 Sick removed a goitre from 
a ten-year-old boy, who was at the time of the operation 
of average mentality ; shortly after the operation the boy 
became stupid and gradually cretinic. In 1883 Riverdin 
and Kocher both published their observations of a cretinic 
condition supervening after removal of the gland. 

The disease, unlike tetany, does not appear till some- 
times weeks or months after the operation, and exhibits 
itself in a loss of mentality, in a chronic edema of the skin, 
and if the operation has been performed in youth the 
growth of both mind and body ceases from that time t)n. 
At first there is only apathy and loss of energy observed, 
but later there is a decided loss of intelligence, the mem- 
ory becomes poor, finally progressing to a complete 
apathy, out of which it is impossible to arouse him. 



SUBGERY OF THE THYBOID GLAND. 119 

Tetany is rarely present, but the sensibility is reduced. 
In some cases the mentality is not much affected though 
the skin changes occur, rendering the diagnosis easy. 

The skin of the face becomes thickened, white, waxlike, 
rough and dry, the sweat and sebaceous glands ceasing to 
functionate ; the hair becomes white and falls out, the ex- 
pression and general appearance gives the impression of 
premature aging, the eyelids swell and hsg. There is an 
edema of the extremities which does not pit on pressure, 
there is also a thickening of the skin in the gluteal region, 
while in the supraclavicular region there are swellings 
which resemble lipomata; the mucous membranes are 
thickened, the tongue and gums swollen, so that the pa- 
tient speaks slowly and with difficulty. 

The blood changes consist in reduction of the red cor- 
puscles, which may fall as low as 2,000,000. There is also 
said to be a leucocytosis. The patient suffers from cold, 
complaining of feeling chilly even in warm rooms. 

Should the operation have been. performed in youth the 
patient ceases to grow in height; the growth in breadth 
increasing out of proportion, the genitalia cease to de- 
velop. The cause of the arrest of growth appears to be 
the arrest of the development of the long bones. In cases 
where the patient has lived into manhood, the epiphyses 
were found unaltered and the ends of the bones not 
ossified. The symptoms vary in degree from complete 
myxedema to slight symptoms which may be difficult to 
recognize. 

The treatment of tetany and cachexia strumipriva con- 
sists in the administration of thyroid gland and in the 
former condition it seems probable that the addition of 
parathyroid gland would be of service. 

Wounds of the thyroid seldom occur. Occasionally in 
cases of suicide, attempted murder, or during the opera- 
tion for tracheotomy the gland may be wounded. In the 



120 • THE THYROID AND PARATHYROID GLANDS. 

two former cases there is, besides the wounding of the 
gland, damage to the vessels, nerves and possibly trachea, 
at the same time. 

The danger in these wounds of the thyroid is the hem- 
orrhage, which may be very severe; if the trachea has 
been cut or the operation of tracheotomy performed, as- 
phyxia may occur by the blood flowing into the trachea. 
Should the gland have been wounded there may follow a 
progressive cirrhotic condition, which may progress to a 
more or less pronounced myxedema. 

In a case seen by the writer, a suicide in cutting across 
the trachea, wounded the thyroid slightly ; on his recovery 
from the wound a band of scar tissue contracted the tra- 
chea, pressing on the gland, causing severe dyspnea. He 
was operated upon and the dyspnea ameliorated, the mel- 
ancholia disappeared later and he was discharged. About 
six months after he returned to the hospital showing many 
of the symptoms of myxedema, yet suffering from acute 
mania. He was put upon thyroid treatment, making a 
very rapid and complete recovery. 



CHAPTER VIL 
THE THYROID IN INFECTIOUS DISEASES. 

The thyroid gland is subject to congestion under the 
normal conditions of puberty, menstruation and preg- 
nancy; at times the congestion becomes so severe as to 
produce dyspnea and asphyxia. This is, however, very 
rare. The patient notices a marked bilateral enlargement 
of the neck, usually accompanied with mental depression, 
an increased pulse rate and slight tremors. If the condi- 
tion occurs at any of the above periods it will completely 
disappear in a few days of its own accord, or there may 
remain a slight permanent enlargement, which will in- 
crease at every succeeding period, progressing to a chronic 
goitre, often ending in degeneration of the gland and con- 
sequent myxedematous symptoms. 

Should treatment be deemed necessary iodid of potas- 
sium or LugoPs solution in full doses will usually reduce 
the tumor in a few weeks. If there is danger of asphyxia 
partial excision of the gland should be resorted to in pref- 
erence to tracheotomy. 

In the acute infectious diseases the thyroid gland often 
suffers more or less severely and many cases of cretinism, 
infantilism and myxedema date from an acute infection. 

The pathological anatomy in these cases has been 
studied by Eoger, who has found that in spite of the 
diversity, of the diseases, which include scarlet fever, 
diphtheria, typhoid fever, cerebrospinal meningitis, 
measles, smallpox and purulent peritonitis, there are a 
number of characteristics common to all. 

To the naked eye the gland a])pears to be normal, but 
is increased both in size and weight. Taking the average 

121 



122 



THE THYBOID AND PABATHYBOID GLANDS. 



weight of the normal adult gland as 25 grms., he has 
found the weight above 30 grms., and as high as 71 grms. 
In these hypertrophied glands the microscopic changes 
are marked. 

The color of the gland is altered from the normal yel- 
lowish tint to a red or violet shade, the parenchyma is 
uniformly red or brownish, marbled with violet. A part 
of the gland, however, may retain its normal color, it be- 
ing not uncommon to find one lobe congested and changed 
in color while the other may be perfectly normal and even 

the affected lobe may not 
be uniformly altered, the 
base being the portion most 
often affected. 

The histological lesions 
are of considerable inter- 
est. The connective tissue 
is in general but little al- 
tered ; sometimes, especial- 
ly in infants, it contains an 
excess of nuclei, but never, 
either in the child or in 
adults, are the masses of 
leucocytes observed which 
are seen in the liver and 
other organs in infectious 
disease. On the first glance 
the impression is given that 
there is a marked increase 
in connective tissue, which is due to the presence of the col- 
loid substance within the vessels. It appears as if thick 
intravascular bands converged towards the vessels, but 
these bands are not foimed from connective tissue. With 
a higher power it is seen that the fibres are eccentric and 
that the intermediate spaces are filled with a homogene- 




FiG. 32.— Congestion of the thyroid. 



THE THYBOID IN INFECTIOUS DISEASES. 123 

ous substance, uniformly colored, giving the reactions of 
colloid substance dilating the lymphatic spaces. The 
whole appears like a network surrounding the vesicles. 
This condition exists in nearly every thyroid gland in in- 
fectious disease. 

The alterations in the vessels are less acute, they are 
dilated and filled with red corpuscles, as are the capil- 
laries. In a case of smallpox the red corpuscles had 
extravasated, mixing with the leucocytes and colloid, 
forming a magma without definite limit in the midst of 
which true thyroid cells could be distinguished, the hem- 
orrhage had remained interstitial. In a case of diphtheria 
the blood had penetrated into the interior of the vesicles, 
but the lesion was limited and affected only a small por- 
tion of the parenchyma. Arteritis and phlebitis occur, 
the intima thickens, progressing into the interior of the 
vessel, producing thrombosis with more or less complete 
obstruction of the lumen. Periarteritis and periphlebitis 
are rare. The most interesting lesions are those of the 
parenchyma, the vesicles being altered in form, dimension 
and constitution, the colloid being sometimes altered in its 
essential qualities. Usually the vesicles are reduced in 
size, as the intravascular vessels are diluted by colloid, 
several of the acini may no longer contain colloid and 
their centre is occupied by cells in a state of disintegra- 
tion. The connective tissue surrounding the vesicle is 
easily made out, but the lining cells have desquamated 
from the wails in many places, and are in the centre of the 
vesicle mixed with the colloid. The protoplasm of these 
cells is granular, the nucleus large, of irregular shape, 
staining badly with hematoxylin. Sometimes several cells 
are massed together in the centre of the vesicle, in the 
midst of which are the nuclei in degeneration. Other 
vesicles on the contrary contain a certain amount of nor- 
mal colloid. 



124 THE THYROID AND PARATHYROID GLANDS. 

The colloid substance does not react to the stains as 
normally. Saf ranin instead of giving it a strong red only 
produces a faint rose color ; sometimes it loses its aflSnity 
for eosin and remains yellow, to aurantium it fails to react 
normally, producing a dirty brown, very different from the 
characteristic light yellow. Occasionally certain vesicles, 
containing instead of colloid a mass of brownish granula- 
tions, fail to take eosin, but become green with thionin. 
Sometimes these granulations fill a whole vesicle or there 
may be only a small mass among the desquamated cells. 
They only exist among the glands, which are much altered. 

When the lesions produced in the thyroid by the infec- 
tious diseases are very marked, the secretion of colloid 
either ceases or is replaced by granulations of abnormal 
reaction. The vesicles are uniformly filled with desqua- 
mated cells crowded together, which have large, clear pro- 
toplasm more rarely granulated. The walls of the ves- 
icles have degenerated and are no longer able to contain 
the colloid substance. 

The pathology of the parathyroids in infectious diseases 
has so far received but little attention. Roger examined 
them in one case of scarlet fever and in a case of diph- 
theria. In the case of a woman dying of scarlet fever, 
where the changes in the thyroid were comparatively 
slight, the four parathyroids showed marked lesions. The 
spaces in the connective tissue instead of being exactly 
filled with epithelium, as in normal glands, were half 
empty. The cells were not dispersed regularly on the 
base membrane, and were massed in the centre of the 
spaces. They consisted of granular protoplasm with ill- 
defined limits. The nucleus stained well. These lesions 
were found in various parts of the gland; at the same 
time there was much healthy tissue. In the case of diph- 
theria they found the same lesions. 

The above are the lesions found to a greater or less 



THE THYBOID IN INFECTIOUS DISEASES. 125 

extent in all infectious diseases ; there are, howeVer, some 
variations distinctive of the different infections. 

In scarlet fever the gland suffers very severely. In 15 
cases examined by Roger only two were found to be about 
normal, one being that of a child of 16 months, the other 
in a woman of 30, but in the latter the parathyroids were 
markedly abnormal. Congestion was always present; 
there was no hemorrhage. The walls of the vessels were 
affected. In two cases endarteritis thrombus was ob- 
served. Hypersecretion of the colloid was observed in 
nearly every case, twice the colloid was altered, reacting 
abnormally to the staining reagents. 

In measles the gland resists the disease better than in 
scarlet fever. In only half of the glands examined was 
there any abnormality observed. 

In smallpox, in the gland of the one case examined, the 
lesions were very severe. The gland was hypertrophied 
and much congested. This case differed from scarlet 
fever in the presence of small parenchymatous hemor- 
rhages, at the same time the colloid was abnormal, being 
brown and granular. 

In diphtheria the hypersecretion is less marked than in 
scarlet fever, the vesicles contain numbers of desquamated 
cells and colloid substance is usually altered; rarely is 
there any hemorrhage. 

The intensity of the lesions does not appear to depend 
on the duration of the disease nor is it affected by inter- 
current diseases. Out of the 15 cases examined, four suc- 
cumbed to streptococcus complications, but showed no 
complication of the lesions. 

In measles it is somewhat diflScult to say what are the 
lesions of the gland in an uncomplicated case, as death 
from measles is rare, the complications usually being 
bronchopneumonia, rarely meningitis, gangrene of the 
pharynx and puinilent coryza. 



126 THE THYROID AND PABATHYBOID GLANDS. 

Garnier made some experiments on animals, inoculating 
them either under the skin or in the veins, and others in 
the thyroid arteries ; under the latter condition the results 
were very instructive. He used the staphylococcus 
aureus, which produced a diffuse thyroiditis; if the cul- 
tures were very virulent they produced parenchymatous 
lesions; if attenuated, interstitial lesions. In the first 
case the vesicles were reduced in size, they contained pale 
colloid, the epithelial cells were swollen, their protoplasm 
staining uniformly, and in places they appeared as fused 
together in a mass, the nucleus was swollen, staining badly, 
the vessels gorged with blood, the connective tissue appar- 
ently normal. If the culture used was extremely virulent 
there were destructive lesions ; with death of the cells the 
vesicle disrupted, the colloid filling the lymph spaces. 

If an attenuated culture was injected there was arteritis ; 
in the vesicles were masses of leucocytes, in the centre of 
which were degenerated epithelial cells. 

The experiments with the typhoid bacillus produced the 
same diverse anatomical lesions, but more diffuse. With 
very virulent cultures hemorrhagic thyroiditis occurred. 
With less virulent cultures there was epithelial degenera- 
tion, capillary congestion and endarteritis. When the 
animals were allowed to survive sclerosis occurred in the 
form of bands of connective tissue, which divided the 
gland into segments. The vesicles appeared to be normal, 
but their walls were much thickened. There was also a 
certain quantity of endarteritis and periarteritis. 

Toni experimented on the same lines with the pneumo- 
coccus, the typhoid bacillus and anthrax. He used less 
virulent cultures than Garnier and therefore did not ob- 
tain such marked results, but the same in kind. These 
experiments show that the infectious diseases produce 
certain lesions in the gland which vary according to the 
intensity of the infection. 



THE THYROID IN INFECTIOUS DISEASES. 127 

Suppurative thyroiditis is not uncommon in the infec- 
tious diseases, and hemorrhagic thyroiditis is rare, occur- 
ring most often in smallpox. Sclerosis of the thyroid 
may occur as the result of any of the acute infectious dis- 
eases, and also in tuberculosis and syphilis, which accounts 
for the numerous cases of myxedema and infantilism 
which occur after a severe illness. The symptoms of 
myxedema may not occur for months or years after the 
disease, the sclerosis progressing slowly. 

When the inoculations were made at a distance from 
the gland, there were but slight pathological changes in 
the glands. The staphylococcus, the typhoid bacillus and 
anthrax produced no lesion that could be detected, the 
streptococcus, however, produced lesions resembling those 
described as occurring in man. 

By injection of diphtheritic toxin into a guinea pig 
Eoger observed lesions in the gland resembling those oc- 
curring in man. The colloid substance leaves the alveoli, 
entering the lymphatics ; at times it is so abundant as to 
entirely mask the vesicles, and in the lakes that form there 
are epithelial cells. At other points the cells desquamate 
into the middle of the vesicles. All the colloid passes into 
the vessels but preserves its normal characteristics. 

The tetanus toxin produced rather different results, the 
lesions were less marked and consisted principally in a 
slight hypersecretion. In one case which developed slow- 
ly the colloid was granular and yellow, taking the stain 
poorly. 

The effect of the inoculations of cultures and of toxins 
upon the gland seems to resemble very much the action 
of nitrate of pilocarpin and iodid in producing a hyper- 
secretion which flows into and gorges the lymphatics, 
dilating the vesicles, and there appears but one vast mass 
of colloid scattered irregularly, among which are rows of 
nuclei, the cells having desquamated and filled the cavity 



128 THE THYKOID AND PARATHYROID GLANDS. 

of the vesicles, their nuclei staining badly, showing ir- 
regular outlines, the colloid remains normal, while in the 
infectious diseases, although the anatomical lesions are the 
same,, the colloid is evidently chemically changed, so that 
while there is a hypersecretion there may also be **dys- 
thyroidation" which may amount to a suppression of 
function of the gland. 

It follows, therefore, that during the course of infectious 
diseases there are secretory troubles in the thyroid gland 
as well as in the other glands of the body, a period of 
superactivity followed by a diminution or alteration of 
function, as the liver secretes abnormal pigments so the 
thyroid secretes abnormal colloid substance. 

Usually the lesions are slight and are quickly repaired, 
but it may not always be so, pathological conditions may 
continue to exist and may be progressive, producing par- 
tial or complete loss of function, accompanied with the 
symptoms of hypo- and athyroidea. 



CHAPTER VIIL 
ACUTE THYROIDITIS. 

Acute inflammations of the thyroid were observed in 
the middle of the seventeenth century, terminating as sup- 
purative goitres. Libert in 1862 and Bauchet in 1877 
wrote monographs on the subject which are classical in 
France. 

Acute thyroiditis is always due to infection, a predis- 
posing cause being a goitrous condition of the gland which 
then becomes cystic. The disease occurs most frequently 
in women, usually between the ages of 20 and 40, occa- 
sionally in children, and very rarely over 50 years of age. 

Among the causes of susceptibility besides goitre are 
trauma and cold. The trauma may be due to pressure, 
such as strangulation. When the inflammation is pre- 
ceded or accompanied by a cold it is due to an infection, 
usually streptococci from a pharyngitis. The gland is 
liable to infection from its circulation, a venous conges- 
tion being easily produced by shouting or long talking, 
during labor, and in various other ways ; it also may occur 
at the climacteric. Nearly always, if not always, thy- 
roiditis is a secondary lesion during the course of an in- 
fectious disease, among the most common being typhoid 
fever. The pus in the gland has been found to contain 
the bacillus of Eberth by Tavel, Kocher and many others,, 
either in pure culture or associated with other organisms. 
Some cases can be attributed to a secondary pyemia, it 
having been observed in purulent infections, posttrau- 
matic, postoperative or other suppurative lesions. It is,, 
however, in puerperal infection that the disease is most: 
common, the organism being usually a streptococcus. 

9 129 



130 THE THYBOID AND PARATHYBOID GLANDS. 

The diseases which may produce acute thyroiditis are 
the eruptive fevers, scarlet fever, measles, smallpox, ery- 
sipelas, diphtheria, influenza, pneumonia, articular rheu- 
matism, and particularly malaria. It has also been ob- 
served to accompany or follow bronchitis, pharyngitis and 
coryza. In diseases of the digestive tract it has been ob- 
served in catarrh of the stomach when the bacillus strep- 
tococcus lanceolatus was isolated, in acute enteritis, and 
in proctitis when the bacillus coli conmaunis was found. 
The staphylococcus pyogenes was found in a gland during 
a case of osteomyelitis. 

The symptoms vary with the accompanying disease. 
Should there be a primary infection of the gland there 
would be the chills, fever, malaise and headache common 
to all infections, followed by the more distinctive symp- 
toms of pain felt in the region of the gland, which is in- 
creased on pressure, localized in the majority of cases in 
one lobe, usually the right; the pain increases on move- 
ment, especially in extension, causing the patient to carry 
his head thrust forward and bent downward so as to relax 
the muscles as much as possible; sometimes supporting 
the chin with the hand ; often the pain radiates to the ears 
and neck. At the end of the first or second day the en- 
larged lobe usually becomes palpable, very rarely the 
tumor is confined to the isthmus. 

On palpation the tumor is found to be attached to the 
deep tissues moving up and down on deglutition, it feels 
at first hard and perhaps elastic ; there may be displace- 
ment of the trachea, which becomes compressed should 
the tumor reach a large size, causing dyspnea, which may 
require prompt surgical interference. 

The compression of the vessels causes distention of the 
superficial veins, headache, singing in the ears, vertigo, 
and sometimes epistaxis. Pressure on the pneumogastric 
nerve may also add to the dyspnea. The patient is an- 



ACUTE THYBOIDITIS. 131 

noyed by a dry cough, accompanied by a slight expectora- 
tion streaked with blood, or there may be true hemoptysis. 
The voice is rough, harsh and thick, speech slow and diffi- 
cult, sometimes the aphonia is absolute. The respiration 
becomes painful and wheezy. There may be pressure on 
the esophagus, or pressure on the nerves, producing pain- 
ful and difficult deglutition, with a feeling as if there were 
a foreign body at the back of the throat; vomiting may be 
very severe. 

The irritation of the various nerves compressed by the 
goitre may cause a number of very varied symptoms, such 
as pains in various regions of the body, formications and 
paralysis of the hands. This latter symptom is said to be 
occasionally produced by a f imctional trouble of the gland. 

Thyroiditis may terminate by resolution, by suppura- 
tion or by gangrene. In the first case the symptoms in- 
crease for three or four days, then remain stationary for 
some days, characterized by fever with matutinal remis- 
sions with a more or less serious condition for five or six 
days. At the end of this time the gland, which has been 
steadily growing, commences to diminish in volume, the 
tumor disappearing in about twenty days. Sometimes 
there is a return of the swelling after a few days. In 
many cases the gland never returns to its former volume, 
remaining permanently enlarged. 

Suppuration occurs in about 60 to 70 per cent of the 
cases, as in all cases of infection there are chills, fever, 
malaise, headache, etc., but there is also a change in the 
character of the pain, which becomes lancinating ; the skin 
over the gland, which has up to this time remained normal 
or slightly streaked with the engorged veins, becomes hot 
and red, losing its mobility over the deeper tissues. The 
cervical region becomes enlarged, accompanied by an 
edema in the substernal region as well as in the upper 
portion of the thorax. 



132 THE THYBOID AND PABATHYBOID GLANDS. 

Fluctuation is always late in appearing and is difficult 
to detect, owing to the depth of the tumor, and is not of 
such symptomatic value as the discolorations and edema 
of the neck. Exploration by puncture will usually have 
to be resorted to if it is necessary to operate early in the 
disease. As the pus is very thick and the tumor perhaps 
a long distance from the surface, even a negative result 
cannot be relied on. 

If the abscess is left alone it usually opens externally ; 
the skin becomes red and taut before perforation, the pus 
is either a serous liquid, fetid, bloody or contains gas. 
Usually cicatrization is rapid, at others a fistula may re- 
main for a month or even years. The abscess may per- 
forate into the larynx, trachea and esophagus, or into the 
surrounding tissue; in the latter case the condition be- 
comes very grave, sinus forming in the direction of the 
face, the neck, the clavicles or the pleura. 

Gangrenous thyroiditis is rare, there being only eight 
cases on record and is of very grave prognosis. The con- 
dition develops rapidly, the gas forming under the skin 
causes distention which rapidly breaks down, leaving a 
large opening in which the carotid arteries and the arch 
of the aorta may be visible. 

A rheumatismal thyroiditis occurs during an acute at- 
tack of rheumatism, never suppurates, and is character- 
ized by a mobile and fugitive congestion, often developing 
with great rapidity within a few hours and disappearing 
in the same manner. The pain in the region of the gland 
is very intense, causing the patient to thrust his head for- 
ward to support his chin with his hand. It rarely lasts 
more than three or four days, though it may return or 
alternate with other manifestations ; the neck may remain 
permanently enlarged. 

The thyroiditis of mumps is somewhat similar in its 
character to that of rheumatism, but is extremely rare and 
has not been observed to suppurate. 



ACUTE THYBOIDITIS. 133 

The thyroiditis of grippe may attain the size of a hen's 
^ggj it recedes about the sixth day and does not suppurate. 
The symptoms which it produces are those of hyperthy- 
roidea, viz : vertigo, palpitations, tachycardia, tremors, etc. 

The thyroiditis of malaria rarely suppurates, except in 
goitrous cases. 

The thyroiditis of typhoid is the most frequent form of 
secondary acute thyroiditis, usually appearing at the com- 
mencement of convalescence, and is probably a local in- 
fection from the bacillus of the disease. When it occurs 
during convalescence there is a rise in temperature with a 
hyperleucocytosis instead of the hypoleucocytosis of the 
typhoid fever. Suppuration is frequent, occurring in 
about 50 per cent. Generally the course is favorable with 
rapid cure. 

Pyemic thyroiditis is a much more grave disease than 
the other forms, as the points of infection are scattered 
through the gland, rendering the probabilities of a favor- 
able termination very remote. 

The pathological anatomy of this condition requires 
only a short description. In non-suppurative conditions 
the tissue is much congested, of a dark red color, dotted 
with small hemorrhages. Under the microscope pigment 
degeneration of the cells is found, congestion of the capil- 
laries and the colloid infiltrated into the interstitial tissue. 

The suppuration is generally in the bands of connective 
tissue, looking under the microscope like small miliary 
abscesses. 

The diagnosis of acute thyroiditis presents but little 
difficulty. The treatment depends upon the cause, it 
being directed to the general infection. A purgative to 
deplete the system has often a good effect in reducing the 
tumor, external application of belladonna ointment or of 
hot compresses may be of service. If there is suppura- 
tion the abscess should be opened as soon as it can be 
definitely defined, usually it will heal up rapidly. 



134 THE THYROID AND PAKATHYBOn) GLANDi?. 

TUBERCULOSIS OF THE THYROID GLAIH). 

The thyroid gland is subject to two kinds of lesions in 
tuberculosis; it may be invaded by the tubercle bacilli 
with the development of the typical granulations, or the 
toxins formed in the general system may produce sclerosis 
and consequent loss of function. Tubercle formation in 
the gland is rare, on the contrary the sclerosis of the gland 
is always present. 

Previous to Lebert's work in 1862 the pathological re- 
search on the thyroid had been principally confined to 
goitre. The latter investigated and found miliary tu- 
bercles in the gland of a woman 25 years of age. Vir- 
cbow reported a case of caseous tubercle, which was fol- 
lowed shortly after by reports of cases by Praenkel, Bruns, 
RoUeston and others. Chiari found tubercles in the thy- 
roid in 4 per cent of his cases. Weigert found tubercles 
in the thyroid of all of the eleven cases of miliary tubercu- 
losis that he examined; others have not found them so 
frequently. They are more common in young persons and 
children than in older patients. 

In certain tubercular patients the tubercles produced 
by the disease cause a swelling of the gland, which may be 
so great as to cause discomfort to the patient, occasionally 
compressing the neighboring organs, producing the vari- 
ous symptoms already described. Fumolard describes a 
form of this infection under the title of follicular thyroid- 
itis, being subacute in its progress, characterized by suc- 
cessive infections, producing fistulous openings. 

In the second form the gland contains caseous nodules, 
but is not so enlarged as to press on the neighboring or- 
gans. In Virchow 's case the nodule was about the size of 
a cherry. In a case of Grasset and Estor's the left lobe 
was double the normal size, hard, covered with small 
tumors, the size of a lentil, on the anterior and superior 
surface, attached to the gland by a pedicle. Rolleston re- 



TUBEBCULOSIS OF THE THYROID GLAND. 135 

ported a case where there was a caseous mass in the gland 
with an abscess having two orifices opening into the 
esophagus, one the size of a ten-cent piece, the other much 
smaller. 

The third form corresponds to miliary tuberculosis, the 
tuberculous granulations are distributed on the surface 
and in the parenchyma of the gland, the granulations are 
yellow and easily distinguished with the naked eye and of 
about the size of a millet seed. Sometimes the granula- 
tions are very small and can only be recognized by the aid 
of the microscope, the gland appearing normal on macro- 
scopical examination and is not increased in volume. 

In the neighborhood of the 
tubercle the gland is pro- 
foundly altered, the position ^ 
of the vesicles is indicated 
by the granular cells, which 
are in circular or elliptical ' 
groups, but poorly stained. 
The cavity of the vesicles 
does not contain colloid but a 
few fibrils surrounding the 
epithelial cells. Between the 

. , ., . . Fig. 33.— Tuberculosis of 

vesicles there is an increase Thyroid. 

of fibrous tissue, enclosing 
numbers of fixed proliferated cells. 

On injecting cultures of the tubercle bacilli into the 
thyroid gland of animals by way of the thyroid artery 
granulations were produced of the same type as those 
found in man. The first effect of the bacillus or its toxin 
is to cause degeneration of the cells. As the most highly 
differentiated elements are always least resistant, the ves- 
icular epithelium was the first attacked. If the cultures 
were very virulent or a large quantity was injected, and 
the organism like that of the guinea pig very susceptible. 




136 THE THYEOID AND PARATHYROID GLANDS. 

this reaction is not marked. If the action is less energetic 
or the resistance greater the reaction occurs. As soon as 
infection has become general, the toxins formed in the 
other parts of the body are brought to the gland by the 
circulation and sclerotic lesions commence. If, on the 
other hand, the baciUi penetrate and find a nidus in the 
gland the quantity of toxin formed produces a more in- 
tense reaction and tubercular granulations. 

Sclerosis of the thyroid is almost invariably found in 
tuberculous disease and has been described by Gamier as 
occurring in eleven out of twelve cases examined. Char- 
rin and Nathan Lerrier showed that it exists in the newly- 
born of tuberculous mothers. In a case described by 
Roger, where the gland was not sclerotic, the gland 
weighed 90 grms., being three times larger than normal, 
containing neither granulations nor sclerosis ; the vesicles 
were filled with colloid and the cells apparently normal. 
It would appear that the existence of a goitre had tended 
to preserve the gland from the action of the toxin. 

It is difficult to determine what symptoms in phthisis, 
if any, are due to sclerosis of the thyroid. The tachycar- 
dia, so often noticed in the early stages of tuberculosis, 
may be produced by a superactivity preceding the destruc- 
tion of the tissue and sclerosis. The sclerosis of the gland 
must necessarily, if going far enough, produce loss of 
function of the gland and may account for some of the 
many varied symptoms which occur in the disease. The 
fact that patients who recover from tuberculosis often 
become very stout may be due to a hypothyroidea pro- 
duced by a sclerotic condition of the gland. 

Gautier and Bourcet have shown that the iodin and ar- 
senic disappear from the gland in tuberculosis, which may 
account for the troubles of the skin and of the menstrual 
function and he claims to have removed these symptoms 



TUBEBCULOSIS OF THE THYBOID GLAND. 137 

by the administration of cacodylate of soda combined with 
very small quantities of iodin. 

A macroscopic examination of the gland shows that it is 
much reduced in size, weighing as low as 8 grms., the sur- 
face is paler than normal on section, the tissue is irregu- 
larly colored, partly yellow and partly pink; the gland is 
harder than normal and in advanced cases the bands of 
connective tissue can be distinctly seen. 

The microscopic examination shows either a pure scle- 
rosis or the latter associated with parenchymatous altera- 
tions. The most common lesion is atrophic sclerosis while 
more rarely there is a hypertrophic sclerosis. 

In trophic sclerosis the connective tissue may be diffuse 
and irregular, at other times regularly distributed, form- 
ing geometrical figures more or less typical. In the first 
case the tissue is abundant, surrounding the vessels in 
concentric circles, giving the idea of a lobular formation. 
The vesicles are compressed between the bands and may 
be empty of colloid. The external walls of the arteries 
are thickened, often accompanied by endarteritis, the 
lumen is decreased and sometimes obliterated. In the 
veins the lesions are usually less marked. 

The parenchyma is little changed, the vesicles appear- 
ing normal, but in certain parts the gland shows a condi- 
tion of functional hyperactivity. The islands of vesicles 
formed by the bands of connective tissue secrete actively, 
the cellular detritus infiltrates into the vesicles while occa- 
sionally the colloid appears in the lymph spaces. Some- 
times the sclerosis is accompanied by the formation of 
abnormal colloid. 

In hypertrophic sclerosis the gland is enlarged and may 
weigh as much as 52 grms., the sclerosis is irregularly 
distributed, and in the neighborhood of the larger vessels 
are large islands of vesicles. The parenchyma is in a 
state of active cell proliferation, the irritation of the toxin 



138 THE THYROID AND PAKATHYROID GLANDS. 

has evidently produced an abnormal multiplication of the 
elements, the cells appearing healthy but of small se- 
cretory power. It is probable that this hypertrophy is 
the first effect of the action of the toxins which progresses 
to atrophy of the gland. 



CHAPTER IX. 
SYPHILIS OF THE THYROID. 

The thyroid gland is sometimes the seat of a syphilitic 
inflammation in secondaries or tertiaries, the gland be- 
coming so large as to cause dyspnea, but this is excep- 
tional. Wolfler records a case where the thyroid was 
found to contain a gumma the size of a fist. Fraenkel 
reports a case which died of syphilis of the trachea, lungs 
and liver. At the autopsy it was found that between the 
isthmus and the right lobe there was a mass of yellow 
substance which, on microscopical examination, proved to 
have developed in the interfoUicular tissue and had com- 
pressed and invaded the parenchyma of the gland. The 
lesion is differentiated from tubercle by the absence of 
giant cells and degeneration. 

Hereditary syphilis is occasionally found in the thyroid 
gland. Demme found small gummas in five cases. FtLrst 
records a case of a child born of a syphilitic mother who 
presented none of the typical symptoms but had a large 
goitre which he considered to be of syphilitic origin. 

Garnier studied the glands of five newly-born syphilitic 
children. In only one case was the gland healthy. The 
lesions were remarkable as being diametrically opposite 
to those found in the adult ; the colloid substance instead 
of being increased was reduced or absent. The vesicles 
were uniformly full of cells, the capillaries dilated, small 
hemorrhagic points scattered through the gland and at 
the same time focuses of cellular degeneration. These 
lesions are not confined to hereditary syphilis but occur 
more or less marked in all cases of infection of the fetus. 
These lesions are of importance as they may account for 

139 



\ 



140 THE THYBOID AND PABATHYBOID GLANDS. 

many of the troubles occurring in the development of the 
child. 

Abraham reports three cases of women who developed 
exophthalmic goitre, the first five months after the pri- 
mary lesion, the second during the height of secondary 
infection, and the third two years after infection, all of 
whom were cured by antisyphilitic treatment. 

Faisans and Audistere reported a case with both gonor- 
rheal and syphilitic infection, who developed a pseudo- 
myxedema in which the myxedematous symptoms were 
not affected by mercurial treatment but disappeared 
under thyroid feeding. 

Kohler has reported cases of myxedema following 
syphilis, and Demme has observed symptoms of Base- 
dow's disease to occur. 

CANCER OF THE THYROID. 

Cancer of the thyroid gland is rare, occurring only 19 
times in 10,000 cases and very rarely except in glands 
which are goitrous. It usually appears between the for- 
tieth and fiftieth year. Schuh observed it in a young man 
of 16, and Demme in a child. Traumatism is probably a 
factor and Kauffraan suggests pregnancy as favoring its 
development, owing to the congestion of the gland during 
that period. 

Usually the tumor is unilateral, but may affect both 
lobes ; the enlargement may be as large as a hen 's egg or 
even greater, being sometimes hard, at others soft. 

Cancer of the thyroid has a tendency to invade the 
neighboring tissue ; the trachea, the larjmx and the esoph- 
agus are compressed by the neoplasm, causing ulceration 
and perforation. 

Thyroid cancer is a tubular epithelioma characterized 
by the development of narrow spaces filled with polygonal 
cells, there being many grades between an adenoma and a 
true cancer. 



CANCER OF THE THYROID. 



141 



The tumdr generally develops in a preexisting goitre, 
probably remaining latent for some time, then developing 
rapidly, the patient dying in five or six months. During 
the course of the disease many of the symptoms of Base- 
dow 's disease occur, at other times the patient complains 
of heat and of sudden congestions of the head, accom- 





^^^^^g? 



Fig. 34.— Columnar celled Carci- 
noma of Thyroid Gland. 



Fig. 35.— Adeno Carcinoma of 
Thyroid Gland. 



panied occasionally by a temperature of 38 or 39 degrees 
C; also the urine shows increased nitrogen elimination, 
albumin or sugar as in Basedow 's disease. There are no 
premonitory symptoms, the patient seeking advice on ac- 
count of the rapid increase in size of the existing goitre. 
Owing to the rapidity of the growth of the tumor and 
its invasion of the neighboring organs, the patient suffers 
from great functional disturbance, the pain radiates to the 
lower jaw, the teeth, the neck, the temples, the ears or 
towards the hands ; violent pains of the stomach are not 
uncommon, probably due to pressure on the pneumo- 
gastric nerve. Compression of the trachea or the recur- 
rent laryngeals causes some dyspnea and strident inspira- 
tion. Should the esophagus be attacked deglutition is 
difficult and painful, sometimes impossible. When there 
is thrombosis the superficial veins of the skin are dilated, 
accompanied by edema of the presternal region. 



142 THE THYKOID AND PARATHYBOID GIANDS. 

Rarely does the patient die from the cachexia but by 
a complication, such as the extension of the disease to the 
lungs which can be recognized by the blood in the sputum 
or by a bronchopneumonia or suffocation. Ulceration of 
the carotids, obliteration of the jugular vein, ulceration 
of the trachea, perforation of the esophagus and ulcera- 
tion of the left carotid all occurred in a case reported by 
Poumet. 

The diagnosis is difficult, exploration with the needle 
is the most likely to give satisfactory results. 

The prognosis is very bad, as medicinal treatment is of 
no avail, and operation is hardly likely to give good re- 
sults, considering that in all probability the whole of the 
gland will have to be removed and that the neighboring 
tissues are more or less involved. 

SABCOMA OF THE THYBOH). 

Sarcoma of the thyroid is rare and, curiously, seems 
to be more common in men than in women. It usually 
develops between the ages of 50 and 60 years. It differs 
from cancer in that it attacks healthy glands more often 
than those affected with goitre. It may grow to a great 
size, having a glossy surface and being of a soft consist- 
ency. It often contains cysts or calcareous deposits. 
Pulsating sarcomas have been observed. 

The tumor develops in the intervesicular connective 
tissue and may be either spindle celled or round celled. 
The evolution is rapid, producing the symptoms of pres- 
sure, etc. The patient usually succumbs within a year of 
the development of the disease. The tumor is usually 
accompanied by the symptoms of Basedow's disease. The 
treatment is extirpation but the prognosis is grave. 

HYDATID CYSTS OF THE THYROID. 

Hydatid cysts of the thyroid are very rare and can only 
be diagnosed by exploration. The syringe will contain 



HYDATID CYSTS OF THE THYROID. 143 

a clear liquid, sometimes purulent. The diagnosis can be 
made with the microscope and by chemical examination 
for succinic acid. 

The treatment consists in opening up the cyst or inject- 
ing iodin, when it heals easily ; should the cyst break into 
the trachea the prognosis is very grave. 



CHAPTER X. 
CRETINISM. 

Myxedema, a disease the result of absence or loss of 
function of the thyroid gland, either congenital or ac- 
quired, was first described in 1873 by Sir William Gull, in 
a paper read before the London Medical Society, entitled 
**A Cretinoid Condition Supervening in Adult Life," in 
which he describes the three principal symptoms as tume- 
faction of the skin, a general cachexia and a cretinoid con- 
dition. Four years later Dr. Ord published observations 
on two similar cases, with an autopsy as well as a chemical 
examination of the skin, giving the disease the name of 
myxedema, since which time the literature on the subject 
has become very voluminous, giving a complete picture of 
the disease and establishing its symptomatology. 

Myxedema is subdivided into cretinism (endemic and 
sporadic), which are cases of congenital absence or loss of 
function of the gland occurring during the first year of 
postnatal life. Infantilism is a term applied when the 
thyroid function is partially or completely lost before 
puberty. The term myxedema is applied to those cases 
where the function is lost during adult life. Between the 
normal condition of the gland and its complete or almost 
complete cessation of function, there are necessarily an 
infinite number of degrees, producing various symptoms 
which it is of great importance to recognize as pointing to 
a possible relief by thyroid feeding and which are classi- 
fied as masked myxedema. There is yet another form of 
infantilism known as ^^Type Loraine'' which appears to 
be only partially due to loss of function of the gland. 
These various forms have one etiological lesion conunon 

144 



CRETINISM. 



145 



to all, viz: the loss of function of the thyroid gland, the 
differences being due to the age at which the disease 
occurs and the amount of functionation lost. 

Endemic cretinism occurs in districts where goitre is 
endemic and almost invariably in the children of goitrous 
parentage; 75 per cent of these cretins are goitrous. 




Fig. 36. — Cretin with goitre. (v. Brims.) 

Theie is no reason to suppose that cases with the same 
etiology as the sporadic form may not occur in goitrous 
districts, but the very large number of cretins in the af- 
fected districts is positive proof that a connection exists 
between endemic goitre and endemic cretinism. Occa- 
sionally a child is born with a small goitre and very rarely 
the goitre may be so large as to impede delivery ; in these 
rare cases it is reasonable to suppose that there is an an- 

10 



146 THE THYHOID AKD PARATHYBOID GLANDg. 

tenatal infection of the fetus through the mother. In by 
far the largest number of cases, however, the goitre does 
not appear till the second year of life, that is after wean- 
ingj when the infection is presumably postnatal. En- 
demic goitre rarely produces mj^edema in the adult, but 
it seems as if when the goitre occurs in early childhood 





Ftc. 37.— CreLin with goitre, (v. Mikuiic^;*} 

the gland ceases to functionate, producing the typical 
sjTnptoms. In the 25 per cent of cases which have no 
goitre but simply an atrophy or congeuital absence of Uie 
gland it is evident that the condition cannot be due to 
either ante- or postnatal infection, with the eontagium 
vivum of endemic goitre, and it is presumable that they 
are the result of the Fame etiological factors which pro* 
duce sporadic cretinism. 



CRETINISM. 



147 



The etiology of sporadic cretinism is by no means defi- 
nitely settled; a certain number of cases may be due to 
the morphological absence of the thyroid gland, but such 
a lusus naturae must be very rare. In the previous 
chapter on thyroiditis it was shown that syphilis and 
tuberculosis in the mother 
produce a hypothyroidea 
in the child and it is prob- 
able that other diseases, 
such as rheumatism, may 
have the same effect. Alco- 
holism in the parents, and 
especially if one or both 
were under the influence 
of liquor at the time of 
coition, has been accused. 
Fletcher ascribes two of 
his cases to this cause and 
other writers about 15 per 
cent of all cases. In Scot- 
land the first-born was 
often feeble-minded and 
known as a * * daft callant, ' ' 
which was popularly sup- 
posed to be due to the in- 
toxication of the parents, 
the wedding festivities being often prolonged for several 
days after the ceremony, during which it was customary 
for the groom and often the bride to drink very freely 
of the national beverage. Consanguinity of the parents, 
impressions received during pregnancy and prolonged 
labor have also been cited as causes, but are probably 
merely coincidences. 

The infectious diseases of the mother which have been 
observed as associated with cretinism in the child are 




Fig. 38.— Cretin, 22 years old. 
(v. Wagner.) 



148 



THE THYROID AND PARATHYROID GLANDS. 



tuberculosis, erysipelas, acute articular rheumatism, ma- 
laria and influenza, which are among the diseases de- 
scribed in the chapter on thyroiditis as producing patho- 
logical conditions of the gland. That the specific organism 
of these diseases should pass the healthy placenta and 
infect the fetus is improbable, but the toxins produced by 

them in the maternal circula- 
tion will certainly circulate 
in the fetus and possibly pro- 
duce disease of the gland. 
These conditions will account 
for a certain number of 
cases, but some other etiolog- 
ical cause must be invoked for 
the majority. 

In the chapter on the physi- 
ological experiments on the 
thyroid gland attention was 
drawn to the experiments of 
Halstead and others, who 
found that in the case of a bitch 
who had had two-thirds of her thyroid gland removed and 
who was impregnated by an unoperated dog she produced 
puppies with thyroid glands twelve times larger than 
normal. This experiment has since been repeated by 
Edmunds with the same results, showing that nature com- 
pensated for the absence of the thyroid secretion in the 
mother by stimulating the growth of the gland in the 
pups. It is probable that the reverse would occur, viz: 
that should the mother have an excess of thyroid secretion 
the gland in the young would not be developed and conse- 
quently the child would show cretinic symptoms after 
weaning, as up to that time it would receive a certain 
amount of the maternal thyroid secretion with the milk. 
In these cases the child would be a cretin, or should the 




Fio. 39.— Cretin. (v. Wagner.) 



CRETINISM. 149 

gland develop to a certain extent the symptoms would 
decrease in proportion to the development of the gland. 

The occurrence of a cretinic condition without goitre, 
where goitre is endemic, suggests that the parenchy- 
matous increase of the maternal gland, in conjunction 
with the normal hypersecretion of pregnancy, prevents 
the development of the fetal gland. The same reasoning 
will account for cases of sporadic cretinism, should the 
maternal gland be hyperexcited during pregnancy from 
any cause, then the fetal gland would fail to develop. 

In support of this theory the following cases have been 
observed: 

A lady who when first seen was between 50 and 60 
years of age, suffering from a large bilateral goitre, with 
tremors, tachycardia and great depression, giving a his- 
tory of being the mother of two girls and five boys, the 
goitre having begun to develop after her third pregnancy, 
and to have steadily progressed. The first four children 
were normal, the two girls were feeble-minded and died 
young, while the youngest boy, though mentally up to the 
average,, weighed at 19 years of age 340 pounds. Another 
case was that of a woman who had a goitre, two of whose 
sons were feeble-minded and one of the daughters devel- 
oped a melancholia at her second pregnancy, recovering 
under thyroid treatment. A third case is that of a woman 
who while pregnant with her youngest child developed a 
large parenchymatous goitre which disappeared a year or 
so after the birth of the child which was a typical cretin. 

In the majority of cases of sporadic cretinism the dis- 
ease of tha gland can be traced to some acute postnatal 
infection which, producing a thyroiditis, arrested the de- 
velopment or partially destroyed the gland. It is by no 
means uncommon to get a history of the child having 
developed normally, both mentally and physically, till a 
few months after some sickness, from which time it has 



150 



THE THYROID AND PARATHYROID GLANDS. 



ceased to grow and the symptoms of cretinism to appear. 
The older the child at the time of the arrest of the thyroid 
fmiction the more incomplete are the symptoms and the 
more diflScult to trace their true cause. 

The etiology of infantilism is the same as that of cret- 
inism, except that it is probably never congenital, the 
lesion of the thyroid only taking place after infancy, the 
function of the gland being decreased and not entirely 
destroyed. 

In myxedema in the adult the cause is the same, being 
a progressive arrest of function of the thyroid gland, the 
result of some disease or traumatism. Women are much 
more liable to this disease than men, the proportion being 





Fig. 40.— Acute thyroiditis. 



Fig. 41.— Suppurative struma of Thy- 
roid gland. 



about five to one, while in cretinism and infantilism the 
sexes are about equal. The susceptibility of women to this 
disease is no doubt the result of the strain thrown upon 
the gland by menstruation and pregnancy, the hyper- 
activity producing cell fatigue with a resulting atrophy. 
Hun and Prudden state that 64 married women with 
myxedema had 300 children and 29 abortions, and prob- 
ably not all the abortions were admitted by the patients ; 
but of 78 patients there were only 14 unmarried. 



CRETINISM. 151 

Pathology.— Th^ indispensable lesion necessary to pro- 
duce myxedema in any of its forms is an abnormality of 
the thyroid gland involving loss of function. Formerly 
the absence or pathological condition of the gland was 
regarded as accidental and not connected with the symp- 
toms, but since the work of Gull, Ord, Schiff, Riverdin, 
and Kocher it has been recognized as the essential cause 
of the disease. The British commission on myxedema de- 
clared in 1884 that there was but one constant anatomical 
lesion in myxedema, the atrophy or abolition of function 
of the thyroid gland. 

The abolition of function may be due to degeneration 
(goitre) or to atrophic sclerosis. Bramwell describes 44 
cases of myxedema with 10 autopsies, in 9 of which no 
trace of the thyroid could be found and in the tenth the 
lobe was the seat of a tumor, which was either congenital 
or followed some infectious disease. In many cases the 
thyroid is represented by a mass of connective or of adi- 
pose tissue, the thyroid arteries being absent. In endemic 
cretinism 25 per cent of the cases show no trace of gland 
tissue, it being re^placed by connective tissue ; in the other 
75 per cent the secretion' is suppressed or perverted, due 
to a degeneration of the gland. 

Virchow daimed that the mental deficiency in cretinism 
was due to premature ossification of the sphenobasilar 
bone, preventing the elongation of the base of the skull ; 
others contended that the pressure of the goitre on the 
carotid arteries prevented a suflScient blood supply to the 
brain, and that the nongoitrous cases were due to insuffi- 
cient cerebral circulation, from narrowing of the cranial 
foramina and other causes. Malcame counted the lamellae- 
of the c^ebellum and found only 300 instead of the normal 
600; this observation was confirmed by others. 

Ord, Virchow and Horsley examined the tissues micro- 
scopically and failed to find any trace of acini or of thyroid! 



152 THE THYROID AND PARATHYROH) GLANDS. 

cells, only a mass of connective tissue occupying the posi- 
tion of the gland. Stilling found the same condition and 
also the absence of the thyroid artery. Langhans sug- 
gested a process of interstitial inflammation of the gland 
with infiltration of the embryonic cells, absolutely compar- 
able with cirrhosis of the liver, 
the sclerotic tissue developing 
little by little, the vessels suc- 
cumbing to endarteritis obliter- 
ans, the acini atrophying and dis- 
appearing. The British com- 
mission decided that the inflam- 
mation commenced in the parietal 
vessels, infiltrating the embryonic 
cells, which inflammation was 
accompanied by a proliferation 
of the endothelium, destroying 
the vessel walls. Under these con- 
ditions the epithelium of the acini 
proliferate, the connective tissue 
of the gland and the parietes of 
the acini become congested with 
^ ,^ ,, ,. , ,, embryonic cells which slowly 

Pig. 42.— Atrophic gland from *; . i . i. 

a case of myxedema. transform mto SclcrotlC tlSSUC. 

The sclerosis little by little stifles 
the glandular tissue, which takes on the appearance of 
islets, which gradually disappear; in short, there is an 
atrophy from interstitial inflammation which develops 
slowly toward a final sclerosis and thus to the suppression 
of the function of the gland. Coulon examined six cases 
and found that in no case was the thyroid entirely absent, 
but that there were tissue and cytological changes, which 
showed that the gland had almost, if not entirely, ceased 
to functionate, the acini being very few and small, appar- 
ently containing little or no colloid, while there was a great 





CRETINISM. 153 

increase of connective tissue. Other investigators have in- 
variably found little or no normal tissue in the gland. 

In cretins persistent thymus is not uncommon, the hypo- 
physis cerebri is sometimes enlarged, sometimes atrophied. 
An observation of great interest is that the thyroid can be 
atrophied in cases when the mentality is nearly normal, 
though the physical condition 
may be distinctly cretinic. 
This observation and the re- 
sults of physiological experi- 
ments with extirpation of the 
thyroid and parathyroids 
has led Brissaud to advance 
the theory that the thyroid 
gland has to do with the 
physical and the parathy- 
roids with the mental de- Fig. 43.-Myxedematous gland. 

velopment. Murray is of 

opinion that the parathyroids have to do with the nervous 
symptoms and the thyroid with the nutrition and assimila- 
tion. 

Coulon points out that in the lower type of cretins the 
small amount of colloid present is of such a consistency as 
to be unable to pass into the lymphatics while in the higher 
types the colloid is mere fluid. 

The skin is in a thickened pseudoedematous condition ; 
there is hypertrophy of the connective tissue with atrophy 
of the sebaceous sudoriferous glands and hair follicles ; on 
microscopical examination there appears to be an increase 
of connective tissue reverted to an embryonic type; the 
fibrils are disassociated and separated by a substance 
which is said to be mucin ; the fibres and fibrils of the con- 
nective tissue are gelatinous and swollen; the interstitial 
lymphatic spaces are enlarged; the cells are hyper- 
trophied; the nuclei enlarged; in fact, a return of the 



154 THE THYROID AND PARATHYBOID GLANDS. 

tissue to an embryonic state. Virchow considers that it 
is not a regressive but an irritative process, analogous to 
phlegmasia dolens or elephantiasis, justifying Charcot's 
nomenclature of * * pachydermia ' ' The subcutaneous layer 
of fat is often very thick. The cutaneous vessels partici- 
pate in the general condition, the walls are thickened, their 
lumen reduced, progressing to obliteration. 

Kopp, a pupil of Langhans, found thickening of the 
walls of the vessels in the nerve trunks, and also in the 
peripheral nerves, the lymph spaces were enlarged, con- 
taining edematous vesicles and fusiform cells. Schultz 
and Benant claim that these findings are not pathognomic 
as they are found in the normal cases as well as in various 
diseases. 

In the central nervous system Hamilton and Boggowitch 
describe alterations in the brain; Custue in the horns of 
the spinal cord; Hadden in the sympathetic. De Quer- 
vain, who examined the nervous system of thyroidecto- 
mized monkeys, dogs and cats, came to the conclusion that 
these lesions are not constant, and that there is no path- 
ognomic lesion of the central nervous system in myxedema. 

Mendil, Lickenstein, Schotten and Kraeplin have ex- 
amined the blood and have found a diminished amount of 
hemoglobin (65 to 68 per cent), the diameter of the red 
corpuscles seemed to be increased (8/i to 10/*), nucleated 
reds were found and in some cases a slight leucocytosis. 
The coagulability of the blood was reduced. The blood is 
poor in proteids and inorganic salts. 

In cretinism and in cases of infantilism Hofmeister 
found an arrest of development of the skeleton ; exact ex- 
periments made on animals showed that the long bones, 
the vertebral column and the pelvis were one-third less 
than in the control animals, the head alone developing nor- 
mally. The epiphyseal nucleus remains cartilaginous, 
failing to ossify, explaining the rachitic appearance. 



CRETINISM. 155 

In advanced cases of myxedema there is often hyper- 
trophy of the left heart, while chronic nephritis may de- 
velop and true edema appear. 

Symptoms.— When cretinism is fully developed during 
intrauterine life, which is very rare, it usually results in 
the death of the fetus, which displays a curious stunted 
conformation of body with redundant skin, thickened cra- 
nial bones, imperfectly formed face and a general irregu- 
larity of development. Those who are unfortunately bom 
alive present a remarkable picture of mental and physical 
deformity, being dwarfed monstrosities with vegetative 
intellects. The fontanelles are larger than normal, the 
hair thick and descending towards the eyebrows, so that 
the forehead appears small, the eyes are dull and expres- 
sionless, being usually half closed; the lids heavy and 
swollen, with only a few eyelashes ; the skin is livid during 
the first month, later becoming a dingy yellow ; the nose is 
flat, the mouth large, the tongue dry and protruding from 
the mouth, the lips thickened and purple, the lower one 
being pendulous, over which the saliva flows continuously. 
The cries are harsh and unnatural; they take the breast 
sluggishly but never refuse it, appearing to be never sat- 
isfied. Should they survive they develop into the lowest 
form of cretinism. 

As a rule however, in both sporadic and endemic forms 
there are usually no symptoms apparent at the birth of 
the child, nor do they appear till the sixth or seventh 
month, the thyroid secretion being probably supplied from 
the mother through the milk. About the time of weaning 
it is observed that the child appears dull and that there is 
a want of proportion in the growth of the limbs and trunk, 
the head being proportionately much larger than the rest 
of the members. As the child ages these symptoms be- 
come much more marked, the extremities becoming short 
and stumpy, the subcutaneous tissue thick and baggy and 



156 THE THYROID AND PARATHYROID GLANDS. 

a goitre may develop with great rapidity. The facies are 
characteristic, the head is out of proportion to the body, 
with frontal insuflSciency and occipital flattening ; the f on- 
tanelles remain open until the eighth or ninth year, and 
sometimes into adult life ; the forehead is low, the base of 
the nose broad, the eyes wide apart and expressionless 
and half closed, with thickened lid and scanty eyebrows ; 
the lips are thick and purple, the lower lip pendulous with 




Fig. 44. Fio. 45. 

A case of sporadic cretinism before and after thyroid feeding. 

(v. Bruns.) 

the saliva running over it; the tongue swollen and pro- 
truding, the cheeks baggy, of a dirty icteroid hue, with- 
out the red patch of health. The teeth are sometimes 
absent or the first dentition appears late, decaying and 
falling out early. There may be no second dentition or it 
may be late in appearing, the teeth being irregular and 
poorly developed, decaying and falling out early; the 
lower jaw may either protrude or retreat, but is rarely 
normal; there is tumefaction of the nasal mucous mem- 
brane causing mouth breathing ; the oars are thickened and 



CRETINISM. 1 o t 

either waxy or purple in appearance. Fatty tumors are 
common in the older children, but wanting in infants ; they 
appear in the supraclavicular region behind the sterno- 
cleidomastoid muscle in the axilla, between the scapulae, 
and in other parts of the body, being often symmetrical 
and attaining at times the size of a hen's egg. The neck 
is short and thick, often with a depression above the 
suprasternal notch. In the endemic form goitre is present 
in 75 per cent of the cases and is nearly always due to 
postnatal infection; very rarely are infants bom with a 
goitre. The spine is crooked, having a posterior curva- 
ture in the cervical region, probably owing to weakness 
of the muscles and a compensating anterior curvature in 
the lower dorsal and lumbar region, causing the abdomen 
to protrude; there is also a lateral curvature developed. 
A pseudoumbilical hernia is generally present but con- 
tains no gut; true inguinal hernia is not uncommon. The 
genitalia are usually small and poorly developed, often 
with various deformities, the testicles do not descend until 
late and sometimes not at all ; the head of the clitoris is 
enlarged, looking like a penis between the edematous labia 
majora. 

The arms are thick, short and puffy, the fingers are 
thickened, the legs are cylindrical, giving the impression 
of props, or they may be bent, resembling rickets ; the feet 
are short and deformed, being too wide for the length, 
the great toe being swollen. The nails on both hands and 
feet are brittle and atrophied or may only be rudimentary. 
The mucous membranes are tumefied, dry and pale, the 
buccal mucous membrane swollen, as is also the palate and 
pharynx, the esophagus, stomach, intestines and rectum 
present a similar appearance, which accounts for the poor 
digestion, assimilation and severe constipation, with occa- 
sional attacks of diarrhea. There is edema of the glottis, 
the gums are puffy, bleeding easily; the tongue is swollen, 



158 



THE THYROID AND PARATHYROH) GLANDS. 



accounting for the thick, peculiar character of the speech. 
The skin is dry, harsh, scaly and thickened, sometimes 
over the whole body, with a baggy appearance as if it were 
too large for its contents ; the thickening may be only in 
patches. At first sight the condition of the skin suggests 
edema, but as on pressure it does not pit, clears up the 
diagnosis ; there is little or no perspiration and the seba- 




FiG. 46. Fig. 47. 

A case of sporadic cretinism aged 6 years before and after thyroid 
feeding, in the author's practice. 

ceous glands fail to secrete, the skin is free from down, 
the pubes and axillae may be hairless or the covering 
sparse, not appearing till very late ; the beard is usually 
absent as are also the eyebrows and eyelashes; the hair 
of the head is coarse, harsh and scant, receding from the 
temples, or the middle line, the scalp is more or less bald; 



CRETINISM. 159 

there may be bald patches in various parts of the head; 
sometimes the hair is very abundant. 

The physical development is arrested, cretins of 15 
years of age may be no more than two feet six or three feet 
high; the lips, nose, ears, hands and feet are cold, the 
temperature is subnormal, and they are very susceptible 
to cold. The respiration is slow. The digestion is very 
indifferent, the food being only partially digested, the 
feces containing undigested proteid, starch and fats ; the 
appetite is usually moderate, but there is a repugnance to 
meat, which is fortunate, as it is not well borne. It will be 
remembered that in a previous chapter the feeding experi- 
ments on thyroidectomized animals showed that proteid 
diet increased the symptoms. Mentally their develop- 
ment is very varied ; in the lowest types voluntary move- 
ment does not exist nor is there any mentality, the facul- 
ties being purely vegetative, *4'homme plante." Others 
again are vegetative and reproductive, *4'hoinme ani- 
mal." Their eyesight is generally fair, but their hearing 
is often defective. Niepee found the auditory foramen con- 
tracted and the ossicles large and spongy. The intellect- 
ual faculties are very limited, as a rule, though by train- 
ing some few can be taught to take some care of them- 
selves and to articulate a few words which they accom- 
pany with exaggerated and ungainly gestures. They are 
dull, stupid and indifferent to their surroundings; some 
are passionate and excitable, being guided in their emo- 
tions rather by instinct than by reason ; they are capable 
of a certain amount of training and though their affec- 
tions are not deep they form attachments to those who 
minister to their wants. Puberty is delayed and may 
never occur at all. Broca states that in true cretinism it 
never occurs. Masturbation is the exception, most of 
them having no sexual desire ; a few have paroxysms of 
great sexual excitement. The disease progresses slowly 



160 



THE THYROID AND PARATHYBOID GLANDS. 



with no tendency to improvement ; they are not, however, 
very susceptible to the diseases of childhood, but usually 
succumb to some pulmonary trouble before 20 years of 




FiQ. 48. — Cretin, aged 12 years, with the permission of Dr. A. C. Roger, 

Fairbault, Minn. 

age, a few live till 40 or even longer. Eachitis is a com- 
mon complication; in fact, it is said that all cretins are 
rachitic, but this is highly improbable, the nondevelop- 
ment and ossification of the epiphyseal nuclei being mis- 



CRETINISM IN ANIMALS. 161 

taken for rachitis which it closely resembles. Asthma is 
a common complication, possibly due in a certain number 
of cases to persistent thymus. 

The blood is low in hemoglobin and in red blood cor- 
puscles, while the arterial blood is of a venous hue from 
its containing a reduced quantity of oxygen. 

The most marked symptom is the shortness of stature, 
in illustration of which Hertoghe, of Antwerp, quotes a 
case which had not grown since his twelfth year, who at 
27 was four feet six inches high and weighed 81 pounds, 
and who grew one inch in three months on thyroid treat- 
ment, and another who had not grown since his four- 
teenth year and at 18 was five feet one inch, weighing 
110 pounds. In these cases the arrest of growth had com- 
menced about puberty, the patient ceasing to increase in 
height but gaining in weight. 

CRETINISM IN ANIMALS. 

Cretinism in animals has occasionally been recorded. 
Eberth in 1878 described a monster calf which he consid- 
ered a cretin. Qurlt in 1877 describes a few cases. In 
South Kensington Museum there is a stuflfed specimen 
and the Royal College of Surgeons possesses the skeleton 
of a typical cretin calf. 

Cretinism appears to occur with curious frequency in 
Dexter-Kerry cattle, a breed which has become popular in 
Engand in recent years. C. 6. Selegmann in the Journal 
of Pathology and Bacteriology for March, 1904, describes, 
the occurrence of cretins in the herds of this particular breed. 
They are usually born prematurely, with short-rounded 
head, depressed nostrils and projecting mandible, combined 
with extreme shortness of the limbs. They have been 
chri stened * * bull dog calves ' ' by the herdsmen. They seem 
to occur with considerable frequency in all herds of this 
breed irrespective of locality. In 1891 one herd produced 
11 



162 



THE THYROID AND PARATHYROID GLANDS. 



seven cretins out of twenty births, or 35 per cent, another 
herd produced twenty-seven calves, five of which were 
cretins or 18.5 per cent. The pregnancies of the cows are 
abnormal; the calf is usually dropped about the sixth, 
seventh or eighth month, the cow's belly begins to swell, 
becoming enormously distended, before the cretin is born ; 




Fig. 49.— Skull of Cretin calf. (C. G. Selegmann. ) 



the cow loses a large quantity of water, decreasing in size 
before labor. When this occurs months or weeks before 
labor, a further abnormal increase followed by a decrease 
may occur. After the birth th^ lochia is more abundant. 
The placenta, instead of coming away in from one half 
to four hours after delivery as normally, is got rid of 
slowly and in fragments, the process often lasting two or 



CRETINISM IN ANIMALS. 163 

three days. The thyroids of the cretin calves examined 
were represented by a couple of more or less rounded 
edematous dark purple colored masses one on each side 
of the trachea, the isthmus being absent. On microscop- 
ical examination the cells appear to be only partially or 
not at all arranged in vesicles, usually forming irregular 
masses or branching columns with or more frequently 
without a lumen. Colloid is commonly absent, occasion- 
ally present in a few vesicles only. Injection of the gland 
substance into cats did not produce the typical fall in 
blood pressure. These observations of Selegmann are of 
great interest and further investigation may show that 
sporadic cretinism may be due to placental disease. 



CHAPTER XL 
MYXEDEMATOUS INFANTILISM. 

Myxedematous infantilism has been defined as an 
anomaly of development characterized by the persistence 
after puberty of the morphological characters of child- 
hood, the arrest of the physical development being often 
accompanied by a general mental deficiency corresponding 
to the physical retardation. 

In 1871 Faneau published an article on f emininism and 
infantilism in the tuberculous. Joflfroy, Bourneville, 
Sollier, Souques, Barety, Fere, Marfans, Guinon, Capitan, 
Richer, Gerard and others published reports of interesting 
cases of femininism, infantilism and senilism, but these 
forms were not recognized in medical literature till the 
last decade, when Brissaud and Hertoghe, of Antwerp, de- 
scribed the etiology, symptoms and treatment. In 1894 
Brissaud, in his lectures on myxedema and cretinism, at 
the Saltpetriere described a less severe form of cretinism, 
consisting of a partial arrest of physical and mental devel- 
opment, at the same time showing to his class a boy of 18 
suffering from thyroid insufficiency, who presented all 
the symptoms of infantilism. Miege in 1895 described the 
condition of the genital organs in these cases and drew 
attention to their arrested development, pointed out that 
many of the cases whose want of development was attri- 
buted to congenital syphilis, or to tuberculosis were really 
suffering from hypothyroidea, drawing attention also to 
the possible connection of giantism, dwarfism, rachitis and 
obesity with an abnormal functionation of the thyroid 
gland. Hertoghe published his observations in the same 
field, assuring that there was no infantilism without insuf- 

164 



INFANTILISM. 165 

ficiency of the thyroid gland. Hofmeister, Gley, Broca, 
Brissaud and others followed, showing in the most conclu- 
sive manner the important part played by the thyroid 
gland in physical and mental development. 

The etiology of infantilism, to be more definite, myxe- 
dematous infantilism, is undoubtedly a lesion of the 
thyroid gland which has resulted in a deficient secretion. 
The cause of this lesion may be, though probably very 
rarely, the result of partial sclerosis of the gland from 
hereditary syphilis or tuberculosis, but in the vast ma- 
jority of cases it will be found on obtaining the history of 
the case that the patient has suffered from some acute 
disease in childhood which has affected the gland, pro- 
ducing a so considerable sclerosis that it is incapacitated 
from secreting sufficient for the needs of the organisms. 

The symptoms of infantilism are those of cretinism in 
an attenuated form, varying with the age at which the 
disease conunenced, and the amount of the destruction of 
tissue in the thyroid gland. The following symptoms 
may appear but will never or rarely all be found in a 
single case. When the physician is consulted upon the 
nondevelopment of a patient, if he finds a few of these 
symptoms, especially if coupled with the history of an 
acute disease antedating the commencement of the arrest 
of development, he is justified in prescribing thyroid 
feeding. 

The patient appears old for his years, short in stature 
but usually of symmetrical proportions, though stout and 
heavy. The face is large, round and moonlike, with a 
stupid surly expression, pale and waxy looking, the scalp 
and the skin of the face are thickened, the eyes somewhat 
wide apart, the mouth large, the nose broad, the hair is 
usually abundant but coarse up to about the twentieth 
year, when baldness commences, the mucous membranes 
are turgid, especially in the nasal passages and larynx, 



166 



THE THYBOID AND PARATHYROID GLANDS. 



causing mouth breathing with a peculiar harsh nasal into- 
nation as if the patient were suflfering from a severe cold ; 




Fig. 50. — Before treatment. 
( Hertoghe. ) 



Fig. 51.— After 6 months' treat- 
ment. (Hertoghe.) 



the tongue may be swollen, which has a characteristic 
effect upon the articulation. The neck is short and thick, 



INFANTILISM. 



167 



the body usually well nourished, but there is a thickening 
of the skin which disguises the outlines of the muscles and 




Fig. t52.— After 1 year's treatment. 
( Ilertoghe. ) 



Fio. 53.— After 2 years* treat- 
ment. (Hertoghe.) 



bones. The hands are thick and of a bluish tinge, the 
veins being distended. The feet are flat, short and broad. 



168 



THE THYROID AND PARATHYBOID GLANDS. 



The hands and feet are cold, suflfering from chilblains in 
winter and fetid perspiration in summer. The skin is dry 
and harsh, perspiration being absent or subnormal. The 
organs of generation remain infantile, at 23 there may be 
no more sexual development than in a normal child of 10. 
In females menstruation is delayed and even when estab- 
lished is scant, irregular and painful. The nondevelop- 
ment of the sexual organs is one of the most constant and 
important symptoms from the diagnostic standpoint, 
though occasionally the organs may be normal. The teeth 

are small, irregular and decay 
early. If the disease com- 
mences in early childhood, the 
abdomen may protrude and 
there may be a slight pseudo- 
umbilical hernia. The limbs 
are often round and straight, 
having the appearance of 
columns. There is a persist- 
ence of the epiphyseal cartil- 
ages which can be distinctly 
seen with the X-rays. 

The mentality is sometimes 
apparently not impaired, the 
child being equal to the aver- 
age; in other cases he is 
mentally dull and can only be taught to read and write 
witli ililViciilty. This diftVrtnu»e between tlie physical and 
mental development lias caused some observers to come 
to tlie eonelusion that on the thyroid gland depends the 
physieal growth while the mental development is asso- 
ciated with the parathyroids. 

There is, ho\\e\ er» a want of mental development in the 
ehiMi>huess ot* the j\Mtieuts; altlunmh their education may 
Iv up to the avcraiie th.ore is an arivst of development in 




Fuj. M.- - Skiajinim of the lunul 
of a typo l^oruine, 17 years oUl. 



INFANTILISM. 



169 



ideas and mode of thought; they are childlike in manners, 
easily provoked to tears or laughter, associating with those 
much younger in years and continuing to take interest in 
the amusements of children; often there is a certain 
amount of effeminacy which suggests sexual perversion. 




Fig. 55. — Skiagram of the hand of a Fio. 56. — Skiagram of the hand of a 
normal child, 6 years old. case of myxedema, 19 years old. 

The pulse and temperature are usually normal, but the 
respiration is often labored and noisy, due to adenoids or 
to hypertrophy of the mucous membranes of the air pas- 
sages. 

Albuminuria and rachitis are two diseases which may 
exist with thyroid insuflSciency, the former may disappear 
under treatment. There is also a hyperazoturia occurring 
at intervals, owing to a retention of nitrogen. 

In weighing the symptoms in these cases the age at 
which the disease developed has to be taken into consid- 
eration, the older the child at the commencement of the 
disease the more obscure and atypical will be the symp- 
toms. 

Infantilism of the type Loraine has been described by 



170 



THE THYROID AND PARATHYROID QLAKD6. 



Brissaud, Loraine, Faneau de la Cour and others as a 
particular form of arrested development, diflfering from 
myxedematous infantilism in many points, and appears to 
be due to a congenital nondevelopment of the arteries, 
sometimes combined with thyroid insuflSciency. Admit- 

__ ^^^^^^^^1 ting that there is such a con- 

I flL|9^1iBI^^I d^t^^^ ^3 congenital nonde- 
j^. ^^ ^^ JK i# velopment of the arteries, in 
^ ^R-»« ^w ■ which the aorta, the renal and 

pulmonary arteries, etc., are 
reduced in size, it is evident 
that with the other organs 
the thyroid will not receive 
suflScient nourishment and 
will consequently be arrested 
in its growth and functiona- 
tion. Much has been written 
for and against the existence 
of a condition of congenital 
narrowing or arrest of de- 
velopment of the aorta and 
blood vessels, but there seems 
to be no reason why such a condition should not exist in 
the blood vessels as in other organs of the body. Suter, 
in the '* Archives of Exp. Path, and Pharm.," vol. xxxix, 
holds that there is no such thing as congenital narrowing 
of the aorta but that the variation in calibre found at 
autopsy is merely a question of greater or less elasticity ; 
in any case, it appears that some aortas are at least more 
elastic than others. Ohlmacher, in his researches on con- 
genital epilepsy, found narrowing of the aorta in nearly 
every case. That aortic narrowing must have far-reach- 
ing pathological effects, from the insuflScient blood supply 
to the various organs and upon the heart from the extra 
work thrown upon it, is evident. A congenital mitral 
stenosis would act in much the same man3er. 




Fig. 67.— Skiagram of the hand of 
a type Loraine, 16 years old. 



INFANTILISM. 



171 




In the form of infantilism under discussion there is an 
hypertrophy of the left ventricle with a high Wood pries- 
sure and small arteries, the pulsation of the aorta cannot 
be felt in the neck, the temperature is subnormal; the 
physical appearance is not 
that of myxedematous infan- 
tilism. The patient is short of 
stature, at the first glance 
looking like a boy, but on 
closer observation he appears 
as a small adult, which has 
been well described as a man 
seen through the large end of 
an opera glass; the shoulders 
are large, the chest narrow, 
the bony projections well 
marked, the muscles without 
being strongly developed are 
distinct, having lost the fatty covering of childhood. He 
is a man in miniature giving the impression of effeminacy 
and debility. 

He may have little or no hair on the face, pubes or in 
the axillaB, the sexual organs are small but developed in 
proportion to his size. The head, which in the myxe- 
dematous form is usually large, is small, the face is often 
pitted with psoriasis, the feet small and flat, the teeth 
decayed, the gums red, irritable and lined with tartar. 
The fontanelles close early and the epiphyses ossify nor- 
mally, differing in this from the myxedematous form. 
Fetid perspiration of the feet is common. Nocturnal in- 
continence of urine is associated with this form of in- 
fantilism. 

It is by no means evident that this form of infantilism 
is directly due to hyposecretion of the thyroid gland; on 
the contrary, it is evident that the arrested development 



Fig. 58.— Skiagram of a normal 
hand, 20 years old. 



172 



THE THYROID AND PARATHYBOH) GLANDS. 



of the circulatory system plays an important part ; other 
glands are probably trophic in their function, the testicles 




Fig. 59. Fig. 60. 

Infantilism aged 19 yrs. 
Before treatment. After 1 year's treatment. 

Heiorht, 4' 6%"; weight, 7G lbs. Height, 4' UVa"; weight, 92 lbs. 



INFANTILISM. 173- 

and ovaries, the thymus, the suprarenals and the spleen 
may all have a function to perform necessary for the com- 
plete and normal development of the organism which has 
not as yet been discovered. Many of these cases, however, 
improve on thyroid treatment, though not so completely 
as in the case of myxedematous infantilism. 

If a skiagraph of the hand or long bones is taken and it 
is found that the epiphyses are ossified it is evident that 
increase in height will not follow any treatment, but 
should the intraosseous cartilage still persist the proba- 
bilities are that thyroid treatment will stimulate growth. 

Anangioplasia, or the congenital diminution of the lumen 
of the larger arteries, is considered as a separate form of 
infantilism by some authors, and has been found associ- 
ated with the lymphatic constitution in many cases of so- 
called idiopathic epilepsy by Ohlmacher. Such a condi- 
tion will produce an arrest of development of the organism 
as a whole, acting upon the various organs of the body, 
reducing their growth and secreting powers. There are 
three quantitative conditions of the circulation required 
for the nutrition, growth and f unctionation of an organ ; 
that is to say, the minimum amount of blood will nourish 
the organ and prevent degeneration from starvation, a 
further quantity is required for growth and a still 
further quantity for functionation, consequently any in- 
terference in the quantity of the blood supply will first 
cause loss of function, a further diminution will arrest 
growth and development, and a still further decrease will 
cause starvation and death. Further, the total quantity 
of blood in circulation will be materially decreased by the 
narrowing of the arteries. 

Other organs besides the thyroid may be implicated in 
causing infantilism. Imperfect action of almost any 
organ of the body can be conceived as arresting develop- 
ment, either physical or mental ; it has been described as 



174 



THE THYROID AND PABATHYBOID GLANDS. 



occurring in disease of the abdominal organs, as the liver 
and pancreas, and especially in that condition of lymphatic 
hypertrophy known as status lymphaticus, in which the 
lymphatic tissues all over the body are enlarged, especially 
the mesenteric and intestinal glands, a persistent thymus 




Fig. 61. Fig. 62. Fio. 63. 

Before treatment. After 4 months* treatment. After 7 months* treatment. 
Infantilism simulating type Loraine, aped 21 years. (Hertoghe.) 

being also generally present. Cardiac lesions, such as 
mitral stenosis, or insufficiency, will also probably produce 
a defective development in the same manner as congenital 
narrowing of the vessels produces a condition which, 
though simulating, is not identical with infantilism. 
There is no doubt the testicles and ovaries have an effect 



INFANTILISM. 175 

upon development, both physical and mental, and certain 
cases of infantilism of the type Loraine are said to have 
been improved by the administration of orchitic extract 
when it was evident that the testicles were poorly de- 
veloped. • 

The close association of the thyroid with the physical 
and mental development, as shown in cretinism and myxe- 
dema, point to its being a probable primary cause in the 
majority of cases, the lesions of the heart, liver, pancreas, 
etc., being secondary to the general want of nutrition. 

Dr. Platauf has described a disease under the name of 
ateleiosis (aT€\£iWw, not arriving at perfection), of which 
a few cases are on record. Dr. Hastings Gifford has de- 
scribed some half dozen cases as follows : The most char- 
acteristic features of this disease are (1) its abrupt onset; 
(2) the absence of perceptible cause; (3) the presence of 
infantilism of a conspicuous kind; (4) the retention of 
unimpaired intelligence, and (5) a special tendency to 
marked delay of development of the sexual system. He 
states the disease may appear at any of the developing 
periods of life and divides them into groups according to 
the age at which they develop. Group I, fetal origin; 
Group II, early childhood; Group III, that period which 
intervenes between childhood and maturity, each present- 
ing special aspects depending on the development at the 
time of the onset of the disease. 

Group 7.— Fetal ateleioses is accompanied by certain of 
the characteristics of microcephaly. There may be no ab- 
normal smallness of the brain when compared with the 
size of the body ; in fact, the brain may be disproportion- 
ately large. It, therefore, seems as though the characters 
of microcephaly were due to the fact that a virtual arrest 
of the brain growth takes place at a time when the brain 
is so small and so undeveloped as to be incapable of per- 
forming its proper functions. In only one of Dr. Gif- 



176 THE THYROID AND PARATHYBOID GLANDS. 

ford's cases was there imbecility together with the physi- 
ognorny which is characteristic of ateleiosis. 

Group IL—IUhe disease is most characteristic when it 
commences in early childhood. It may occur in more 
than one member of the same family and in one of his 
cases the father was a dwarf who had been exhibited. The 
disease resembles cretinism in the almost complete arrest 
of growth and development. The form of the body re- 
mains for the rest of life with those infantile characters 
which it possessed at the time of the onset of the disease. 
The stature is preternaturally short, while the head is 
large when compared with the adult, the face is broad and 
flat, the nose sunken at the bridge, while the head is high 
when measured from the ear to the vertex. The childlike 
form and physiognomy, added to a look of independence 
combined with the wrinkling and weltering of the skin, 
give an appearance which is not that of a child or of a 
cretin ( T), and is still less like that of an ordinary adult. 

In describing a case Dr. Gifford says the patient was 
28 years old at the time of the description. He had ceased 
to grow normally at 18 months and by measurement he 
continued to grow till his twenty-seventh year. He left 
school at 16, after passing the sixth standard. ^'His gen- 
eral configuration is that of a child, the outlines of tlie 
muscles are hidden by fat while the contour of both body 
and limbs is rounded and childish in appearance. He is 
3 feet 7^ inches tall, and his head 19^ inches in circum- 
ference, and weighs 57 pounds. His head is large, his 
limbs short, and the relative lengths of the segments of 
the limbs more nearly resemble those of a child than of 
an adult. His height is equal to that of an average child 
between 6 and 7. By means of the radiograph the bones 
of the hand and wrist were examined, showing ossification 
equal to that of an average boy of 13. On the other hand, 
his sexual organs are no more developed than are those of ' 



INFANTILISM. 



177 



an infant. It will be seen that the rate of development of 
different parts is by no means uniform." 

A second ease is described by Dr. Gifford, as follows: 
**He has the broad, flat face and retrousse nose of child- 
hood, but combined with it is the harsh and wrinkled skin 




Fio. 64. 

Normal boy, 17 years 

of age. 



Fio. 65. 

Type I^iraine, 27 

years of age. 



Fig. 66. 

Myxodeinatoiis Infantilism, 

18 years of age. 



of middle age. The countenance is of the cretinoid type, 
but it differs from that of cretinism in that the lips are not 
thick and that the whole face is lighted up by a look of 
intelligence. Sexual hair is completely absent from the 
face as from every other part, but the hair of the head is 

12 



178 THE THYBOID AND PARATHYROID GLANDS. 

fairly abundant and encroaches upon the forehead in a way 
which is more often seen in children than in adults. His 
muscular strength is equal to that of a child of his height. 
All the organs of secretion and special sense appear to be 
normal. He sweats on exertion and is not particularly 
sensitive to cold. His voice is more treble than that of an 
adult. The thyroid gland can be detected. Dentition is 
backward, the permanent canines having apparently not 
long protruded through the gums, while the temporary 
canines of the left side have not been shed. His general 
health is excellent, and he shows no signs of syphilis, 
rickets or of any other disease.'' His age is not stated. 

Dr. Gifford does not state the treatment, if any, nor the 
result, but it seems as if the majority of the symptoms 
described in both cases were those of myxedema, possibly 
associated with a pathological condition of some other 
organ which modified the disease, making it atypic. 

Group ///.— Ateleiosis of this group beginning in adult 
life is not so typical in physical features as the first two 
groups. In these cases there is a curious combination of 
the size and facial characters of a boy combined with the 
mannerisms of an adult. The skin, however, has not the 
soft, delicate tinge of youth, but is more like that of the 
aged or weather-beaten face of grown-up people. In 
ateleiosis there is at times a normal development of the 
sexual organs with powers of reproduction and the bones 
may ossify normally at puberty. 

The description of this group is meagre, but shows 
little or no evidence of myxedeira, and applies more to 
those who have remained childish from the want of proper 
environment. 

Senilism is another form of disease often commencing 
in early cliildhood, which may be mentioned here as it may 
possibly be due to a hypersecretion of the thyroid. 

Normal senilism may occur at various ages, some be- 



INFANTILISM. 179 

coming senile at 55 or 60, others again being vigorous in 
both mind, and body at 80 or more. This normal senilism 
is due to the changes in the arteries and the chemical 
activity of the cells. 

On the other hand, precocious development is an indica- 
tion of disease and a sign usually of early decay. Sexual 
precocity is probably the most common symptom, some- 
times combined with rapid growth in height and weight. 
A well-known case of great premature development is that 
of Thomas Hall, known as the ''fat boy of Willingham." 
In his case there was a premature development of the 
sexual organs at the ninth month ; at 3 years of age he was 
3 feet 9 inches tall and weighed 56 pounds, and his muscu- 
lar strength was equal to boys of 7 or 8 years. His voice 
was ''changed." His intelligence was above the average 
for his age, while his sexual organs resembled in size those 
of a man. At the age of 5 he began to grow a mustache ; 
at six he died of consumption. 

In another case the first dentition began at 10 months, 
the child could walk at 12 months, and at 13 months he 
was 3 feet high and weighed 57 pounds, the head being 
20f inches in circumference. His mentality was about 
equal to his years, he was weak, not being able to sit up 
straight without support, and there was an enormous 
growth of subcutaneous fat; the skin was pale and un- 
healthy. On close inspection coarse dark bristly hair 
could be seen sprinkled sparsely over the body and limbs ; 
that on the upper lip and on both sides of the face being 
longer than elsewhere and resembling in quantity that 
which grows at puberty in normal boys. His sexual or- 
gans were about equal to those of a boy at puberty. He 
suffered from syncope and died in a sudden attack at the 
age of 14 months. 

Progeria is a fonn of senilism which simulates ateleiosis, 
being characterized according to Dr. OiflFord by its abrupt 



180 THE THYROID ANp PARATHYBOID GLANDS. 

onset, the absence of perceptible cause, the presence of a 
conspicuous form of senilism, the retention of intelligence. 
Only two cases appear to have been reported, in one of 
which a postmortem examination showed atheromatous 
conditions of the arteries and the valves of the heart, 
which would account for most of the symptoms.^ 

Yet another form of senilism has been reported by Drs. 
A. S. and T. B. Charcot, in La Nouvelle Iconographie de 
la Saltpetriere, and named by them **geromorphinicu- 
tanee.'' The patient was a young woman of 20, having 
the appearance of being 60 years of age owing to the skin 
hanging in loose folds so that at the neck it hung down 
like the dewlaps of an ox. In the other cases of progeria 
reported there was atrophy of the hair, nails and breasts, 
though in the above case these symptoms were not present. 

Achondroplasia is a form of arrested development which 
may be mistaken at first sight for myxedematous infan- 
tilism. It was first described by Parrot and Depaul in 
France and by Kirchberg and Marchand in Germany, Dr. 
Porak writing a monograph on the disease in the Nouvelles 
arch. d'Obst. et de Gyn., 1889-90. In 1892 Kaufmann 
studied three skeletons of fetal achondroplasia. In 1893 
Thomson reported a case, Apert, Hergott and Marie other 
cases in 1900. 

The disease is usually mistaken for rachitis; the most 
marked traits are the large size of the head and trunk, the 
shortness of the limbs, the forearm and the leg being 
longer than the arm and thigh respectively. 

The symptoms consist of a macrocephalic condition 
which may simulate hydrocephalus ; the head is round, the 
frontal and parietal bones projecting, the face large, the 
features gross, the root of the nose depressed, the nose en- 
larged and rounded at the end, the nostrils dilated, the 
roof of the mouth arched. The depression at the juncture 
of the lumbar vertebrae with the sacrum is verv marked, 



INFANTILISM. 



181 



the latter being elevated, giving the impression of a dislo- 
cation. The hands are small and square, reduced in all 
dimensions, the fingers shriveled and of almost equal di- 




Fi(j. 67. 



Fig. 08. 



Achondroplasia. (Comby.) 



mensions. Sometimes the legs are bowed, at others the 
knees are inclined inwards. The muscles are usually ab- 
normally developed and they are often athletic dwarfs. 



182 THE THYKOID AND PARATHYBOID GLANDS. 

The genitalia are well developed, many of them having 
families. 

The bones which develop directly from the primitive 
embryonic tissue, as the clavicle, ribs, frontal and parietal 
bones, etc., which do not pass through the cartilaginous 
stage, escape the dystrophy, which explains the normal 
development of the trunk. On the other hand, the ossifi- 
cation of the epiphyseal cartilage is arrested, the bones of 
the limbs are unable to lengthen. In distinction from 
rachitis, achondroplasia usually commences from the third 
to the sixth month of intrauterine life, while rachitis is a 
postnatal disease. In achondroplasia there is penetration 
of the periosteum inward, between the epiphysis and the 
diaphysis, which is not seen in cretinism or rachitis. 



CHAPTER XIL 
MYXEDEMA. 

Myxedema in the adult is usually a slowly progressive 
disease, though cases are on record where it has developed 
rapidly. Charcot and Ord report cases which commenced 
with a chill, in one case with hematuria, developing within 
a week. Byrom Bramwell states that in one of his cases 
the disease appeared in a few days after an attack of in- 
fluenza. It is probable that in these cases the disease had 
been latent, unobserved by the patient for some time, until 
some intercurrent disease made a call upon the gland for 
an increase of secretion to which it was unable to respond. 

The initial symptom is an intense lassitude and debility.. 
Women who have heretofore been bright and active in 
their duties have a repugnance to exertion both of body 
and mind. This is associated with an increase of bulk of 
the body, a dryness of the skin and an increased suscepti- 
bility to cold. I have observed that in the very early 
stages there is a hyperactivity of the sebaceous glands, the 
surface of the skin being greasy, while the head is full of 
dandruff. Frontal headache is often a cause of complaint 
in the earliest stages. As the disease advances the face, 
trunk and limbs increase in bulk with the appearance of 
edema, except that the skin does not pit on pressure nor 
does it exude fluid on puncture ; there is an appearance as 
if the skin were too large, hanging in thick folds on vari- 
ous parts of the body. Ordinary dropsy of the feet occurs 
in about 20 per cent of the cases. 

At the first glance the observer notices a heavy, stolid 
expression of sorrowful immobility, the face is full, broad, 
coarse and round, looking puffy and swollen ; in some cases 

183 



184 



THE THYROID AND PARATHYBOID GLANDS. 



the wrinkles are flattened out; tlie upper eyelids droop 
over the eyeballs, causing a eoiisequeut elevation of th<* 
eyebrowSj prndiicing transverse wrinkles in the forehead 
as in paralytic ptosis. Sometimes the lids are so swollen 
that thej' completely cover the eyeball and the patient has 
to raise them with the finger in order to see at all- The 
skin of the eyelid has a jieculiar translucent appearance. 




Baggj^ swellings appear under the eyes, which suggest 
Bright -s dit^ease, Tlie cheeks are pendulous nnd puflfy. 
The thickening of the skin usually comniences in the scalp 
anterior to the ears? and in the nasolabial folds. Owing to 
tlie capillary dilatation there is often a rosy tinge over the 
malar boue, abruptly limited by the lower margin of the 
orbit, contrasting strongly with the dingy yellow color of 



MYXEDEMA. 185 

the rest of the face. The lips are thickened, especially the 
lower, of a purplish color, feeling firm and tense to the 
touch. The tongue is swollen, the gums edematous, bleed- 
ing easily, the buccal mucous membrane is also edematous, 
sometimes to such an extent as to be injured during mas- 
tication. The tonsils are enlarged, the uvula, pharynx 
and larynx are edematous. The swelling of the soft parts 
/)f the back of the mouth may be so considerable that the 
patient may experience difficulty in swallowing, complain- 
ing of a choking sensation. The nose is broad and coarse 
looking, the mucous membranes of the retronasal cavities 
are swollen, impeding respiration, which becomes aggra- 
vated with the least cold. The patient usually complains 
of easily catching cold, of a frontal headache and of a 
^* stopped up" feeling, such as is associated with acute 
coryza. 

The neck is usually broad and thick, with puffy elastic 
swellings above the clavicles. Though the neck appears 
thick the rings of the trachea can be distinctly felt and yet 
the thyroid may not be palpable. It is, however, very dif- 
ficult to palpate the thyroid gland during life even in the 
healthy subject, and it can be assumed that if it can be so 
detected it has increased in size. 

The hands are enlarged, thickened and spadelike, the 
fingers broad, thickened and flat, the patient complains 
that they feel numb and that they are unable to perform 
the finer movements, such as sewing or buttoning the 
clothes; in some cases the swelling is so great that they 
are unable to close the hands; the feet present the same 
changes and, as before stated, there may be true edema 
of the feet and ankles. The abdomen is full and large, 
the trunk as a whole being increased in size ; the vulva and 
external genitals may be swollen. 

The skin is coarse, harsh, rough, dry and scaly looking, 
it may be split up into lozenge-shaped areas, wrinkled and 



186 THE THYROID AND PARATHYBOID OLAND6. 

cracked, resembling ichthyosis. The sudoriferons and 
sebaceous glands cease to secrete, the absence of sweating, 
even in hot weather or after muscular exertion, is a very 
characteristic symptom. The electrical resistance of the 
skin is much increased owing to its dry condition. Byrom 
Bramwell notes the presence of flat moles and warts. On 
the abdomen appear patches of yellow discoloration re- 
sembling the so-called liver spots; there is often a very 
marked desquamation, so much so that the scurf can be 
scraped from the bed linen in quantity. The hair of the 
scalp has a tendency to fall out, complete baldness occa- 
sionally occurring with great rapidity, the eyelashes 
and eyebrows become thin and may fall out entirely. 
There is an incrustation on the scalp, eyebrows and eye- 
lids. The fine hairs at the back of the neck fall out and 
give a peculiar bare appearance. The hair becomes 
coarse and brittle and may change color. In the axillae 
and the pubes the hair falls out, the parts may become 
quite bare. 

The nails are brittle, dry and opaque, the teeth carious 
and loose ; in many cases there is an increased secretion of 
saliva which may be very troublesome. It has been ob- 
served that the secretion from the parotid gland in these 
cases contains an excess of mucus. There is also a run- 
ning from the eyes and nose. 

The mucous membranes of the stomach, intestines and 
rectum share in the general tumefaction of the mucous 
membranes, producing malnutrition and the obstinate con- 
stipation from which the patients invariably suffer. The 
stomach examination after the Salzer-Ewald testmeal 
shows a marked hypochlorhydria, sometimes anachlorhy- 
dria, usually with excess of organic acid, also excess of 
mucus, want of motility and of absorption. 

There is a wheezing inspiration in advanced cases which 
is often ascribed to asthma, the patient may make a noisy 



MYXEDEMA. 187 

gasping inspiration after a sentence. From tlie edematous 
condition of the nasal mucous membrane the patients are 
compelled to breathe through the mouth, consequently 
their intonation is harsh, rasping and nasal ; when adenoid 
growths are present, which is often the case, the breathing 
is noisy even at rest. Owing to the thickening of the 
vocal cords and the enlargement of the tongue the speech 
has a peculiar sound as if the patient had something in 
her mouth. Owing to the impaired mentality the speech 
is slow and deliberate. 

The mental condition is always abnormal, resembling 
dementia; there is a lack of quickness of perception, a 
slowness of thought, an emotional depression and suppres- 
sion combined with listlessness and torpor ; the repugnance 
to exertion of any kind is a marked feature and is often 
the first symptom noticed by the patient. Hallucinations 
of sight and hearing are not uncommon ; there may be a 
singing in the ears and even ' ' hearing voices. ' ' The hallu- 
cinations of sight resemble those of alcoholism ; less often 
hallucinations of taste and smell occur, any of which may 
be so severe as to prevent the patient from sleeping ; as a 
rule, however, patients sleep well or excessively. Some 
few are garrulous, continuing to talk regardless of ques- 
tions or interruptions, simulating mania. Usually these 
patients are even tempered, but sometimes very irritable, 
having violent fits of passion; others are suspicious of 
their friends and of themselves. The memory is much 
impaired. The placidity and stolidity of myxedema is in 
marked contrast to the excitability and perpetual unrest 
of Basedow's disease. The mental symptoms may become 
so severe as to be insanity, rarely maniacal. They arc 
usually melancholic. 

The tactile sensibility of the skin is delayed or dimin- 
ished, sight and hearing impaired. Headache, cramps, 
neuralgic pains, faintness, giddiness, tinnitus aurium and 
muscular pains are often accompanying symptoms. 



188 THE THYBOID AND PARATHYBOID GLANDS. 

The gait is heavy and clumsy, the muscular power is 
much impaired and there is a certain amount of loss of 
coordination, the patient being apt to stagger and even to 
fall. The walk, owing to the increased size of the body 
and the muscular weakness, combined with the slowness 
and numbness of the movements, has been termed the 
' * hippopotamus gait. ' ' 

The reflexes are usually diminished, the knee jerks often 
abolished. The sensibility is often especially impaired in 
regard to heat and cold, the patients being extremely sus- 
ceptible to variations in external temperature, complaining 
of feeling cold. It has been observed by Horsley and 
others that thyroidectomized animals would survive the 
operation much longer and symptoms even not developed 
at all as long as the subject was kept in a room at a high 
temperature. The patients often complain of a tingling or 
pricking sensation of the skin. The body temperature is 
subnormal, being 96.5 degrees F. or even a little lower. 
The subnormal temperature and the susceptibility to cold 
are due to decreased oxidation and a pathologic condition 
of the cutaneous capillary system. 

The pulse is slower than normal, soft and weak, the 
heart's action feeble, the second sound accentuated, the 
mean blood pressure increased, the heart dilated, the car- 
diac muscle degenerated and the arteries atheromatous; 
in the latter case thyroid feeding must be conducted with 
caution. Fainting may occur, palpitation is often com- 
plained of after exertion. Anemia is usually present, the 
hemoglobin may be as low as 60 per cent and the red 
corpuscles reduced to 3,000,000. 

The appetite is poor, as is the digestion ; obstinate con- 
stipation is the rule, diarrhea the exception, but as is com- 
mon in hypochlorhydria, there are often severe attacks of 
diarrhea without apparent cause. 

In females amenorrhea is the rule, menorrhagia the ex- 



INCOMPLETE MYXEDEMA IN ADULT. 1 HO 

ception. In cases of amenorrhea there may be occasional 
profuse hemorrhages ; there is also a marked tendency to 
hemorrhage owing to the high mean pressure and disease 
of the vessels as well as to the reduced coagulability of 
the blood. Epistaxis and bleeding from the gums are 
common, any small injury may bleed profusely. Should 
a case become pregnant, which rarely happens, postpartem 
hemorrhage should be guarded against. 

The urine is usually normal or increased in quantity, 
the specific gravity low, total nitrogen low, urea nitrogen 
decreased, ammonia nitrogen increased, uric acid nitrogen 
decreased or normal, and the residual nitrogen increased. 
The carbon nitrogen factor is high, the carbon elimination 
being greater than the nitrogen; oxalic acid is often in- 
creased, total sulphates are low, ethereal sulphates high 
and the neutral sulphur very high. Indican is excessive, 
bile pigment and indoxylglycuronic acid are often present, 
the latter sometimes in sufficient quantity to reduce Fehl- 
ing's solution. Albumin is sometimes present, and albu- 
mose. Byrom Bramwell reports a case where serum 
globulin was present but no serum albumin. It would 
have been interesting in this case to have had an analysis 
of the blood, in order to have observed the proportion of 
serum albumin and serum globulin. I have found nucleo- 
albumin in several cases, but rarely serum globulin or 
serum albumin, except in cases where there was evidently 
an associated kidney lesion. 

INCOMPLETE MYXEDEMA IN THE ADULT. 

Between the healthy condition of the gland and its com- 
plete or almost complete cessation of function there are 
necessarily an infinite number of degi-ees producing vary- 
ing symptoms, more or less acute, giving varied clinical 
pictures, which it is of importance to recognize as pointing 
to possible relief by thyroid feeding. In the cases where 



190 THE THYROID AND PARATHYBOIP GLANDS. 

there is a hypothyroidea, either congenital or acquired, a 
condition of premature senility is produced, the patient 
appears old for her years, she becomes gray early, either 
generally or in patches, the hair may fall out rapidly either 
over the temples in front, along the median line or at the 
back of the head, the down on the back of the neck disap- 
pears and there is a baldness extending up to the occipital 
protuberance, where it looks scanty and ragged, the skin is 
yellow, shriveled and coarse, the hair feels brittle and dry 
and is fluffy, looking untidy; there is an incrustation of 
the scalp or there may be a large quantity of dandruff, 
sometimes there are bald patches. These changes are 
often concealed by the barber's art and must be especially 
looked for. The eyebrows and eyelashes are thin or may 
be entirely absent; there is a scaly condition of the skin 
at the external angles of the eyebrows, often accompanied 
with itching. The teeth are generally decayed, especially 
the molars; the gums are inflamed and soft, bleeding 
easily; the teeth are covered with black or green tartar, 
rarely yellow, especially the incisors of the lower jaw. 
The tongue is swollen and indented with the teeth. The 
nasal accumulation of tartar forces back the gums, the 
teeth become loose and fall out. The tonsils are swollen, 
often hiypertrophied. The mucous membrane of the 
pharynx is red and edematous, adenoids are often present. 
The fossae are contracted, being obstructed by the swollen 
mucous membrane; adenoids are common; sometimes in 
mild cases the nasal fossae are normal except during men- 
struation or a slight cold, when the posterior portions 
become engorged ; the nasal condition causes the patient a 
great deal of inconvenience, and is generally attributed to 
a chronic catarrh to which the patient ascribes her mental 
heaviness and drowsiness. Sometimes the condition pro- 
duces continued sneezing. The voice is high pitched and 
leathery, usually being more discordant during menstrua- 
tion and pregnancy. 



INCOMPLETE MYXEDEMA IN ADULT. 191 

The headaches which are -often attributed to cerebral 
anemia are of two kinds, sometimes appearing in the 
frontal sinus or behind the orbits, as in acute coryza, or 
they may appear in the occipital region. They are often 
described as migraine, but they differ from true migraine 
in being at their worst in the morning, disappearing as the 
day wears on or after a full meal. The patient is so accus- 
tomed to this that she may not complain of it till her atten- 
tion is called to it ; she usually attributes the falling out of 
the hair or its turning gray to these headaches, or again 
she may account for the headaches by the condition of her 
teeth. The thickening of the skin, which is so marked a 
symptom in complete myxedema, is not present, or only 
very slightly ; there may be a puffiness under the eyes, a 
red patch on the cheek extending to the nose ; the skin has 
a dirty yellow color or it may have a clear waxy appear- 
ance ; the raised eyebrows and transverse wrinkles of the 
brow may also be present ; the whole expression is one of 
sorrowful fatigue. Murray, in the Brit. Med. Jour., 1898, 
describes cases which he calls *' early thyroidal fibrosis, " in 
which he has observed hallucinations of sight and hearing, 
the patients seeing objects indistinctly defined resembling 
cats, mice, rats, etc., which rapidly traverse the room when 
it is well lighted. Buzzing and ringing in the ears is com- 
mon and may go so far as to take the distinct sound of bells. 
Hertoghe has made the same observation. 

There is also a rachialgia with pain between the should- 
ers the patient suffering from insomnia, falling into a 
sound sleep in the early hours of the morning, but is 
shortly awakened with pains which she describes as though 
the back were being wrenched asunder, so intense is the 
discomfort that sleepy and tired though the patient feels, 
she is unable to remain in bed and rises tired and unre- 
freshed, with a headache and rachialgic pains, which, how- 
ever, become less, disappearing entirely as the day ad- 



192 



THE THYROID AND PARATHYROID GLANDS. 



vances only to appear again on the following morning. 
Often the joints and muscles are painful, usually attrib- 
uted to rheumatism, but the temperature is normal or sub- 
normal and the pains do not yield to rheumatic treatment ; 
as the case advances the pains may appear first in one 
part and then in another, or in several places at once. The 
patient often complains of chills, which may occur with 
great regularity at a given time of the day, usually be- 





Fig. 70.— Before treatment. Fio. 71. — After months' treatment. 

Incomplete Myxedema. 

tween 4 and 6 o'clock; they simulate malaria, but the 
Plasmodia are not present nor do they yield to quinin. 
The patient complains of feeling cold in spite of coverings 
and wraps, the feet and hands being especially susceptible. 
A shortness of breath is a very constant symptom, some- 
times very slight and only noticeable on muscular exertion 
or going upstairs; at times it is accentuated. Occasion- 
ally, in advanced cases, the patient makes a quick, short 
noisy inspiration after each sentence, usually ascribed to 
asthma or embonpoint. This oppression exists even when 
the patient is not stout, and on careful examination of the 



INCOMPLETE MYXEDEMA IN ADULT. 



193 



chest dilatation of the base of the thorax will be found. 
Pulmonary emphysema is often diflBcult to explain and 
may be looked upon as pulmonary senility; as hypothyroi- 
dea produces premature senility, emphysema is the senile 
change in the lung corresponding to the graying of the 
hair. The oppression of respiration is often accompanied 
by palpitation and lancinating pains over the region of the 





Fig. 72.— Before treatment. Fig. 73.— After 10 months' treatment. 

Incomplete Myxedema. 



heart, resembling angina pectoris. There is often dilata- 
tion of the left heart and aortic insufficiency, the result of 
the increased mean blood pressure from the contraction of 
the arterioles and capillaries of the skin. 

The venous system suffers from the premature senility, 
varices, varicoceles and hemorrhoids are common, the 
veins in the back of the hands are dilated, even in the 
young and sometimes on the anterior surface of the thorax. 
The capillary system suffers with the rest of the vessels, 
as shown by the dry, harsh desquamatory condition of the 
skin; the red patches on the cheeks, the condition of the 

13 



194 THE THYBOID AND PAKATHYBOID GLANDS. 

gums and mucous membranes. Of the changes in the 
arterial system the loss of tonicity is the most marked. 

The liver often becomes congested. Ver Ecker has 
shown that thyroidectomized animals have a marked con- 
gestion of the liver ; Berkeley observed a general passive 
congestion of the organs in mice poisoned by thyroid feed- 
ing. In mild cases the liver is simply enlarged, in more 
advanced cases the patients complain of a weight in the 
hepatic region ; there is also pain over the gall bladder and 
gall stones are frequently present. 

The symptom which seems to predominate in all cases 
of hypothyroidea, whether in cretinism, myxedema or in 
the incomplete forms, is obstinate constipation ; to this the 
patient often ascribes all her ailments. 

Amenorrhea and dysmenorrhea are the rule; there is 
also retroflexion of the uterus even in the young, due to 
imperfect development of the posterior wall of the uterus, 
fibromas are often present, to the retroflexion and the 
fibromas the gynecologist ascribes all the symptoms, but 
operation fails to relieve the patient Impotence and loss 
of sexual desire are a common cause of patients seeking 
advice. 

Owing to the increased activity of the gland during 
pregnancy the patient is often in better health during this 
period, the extra secretion being utilized by the maternal 
system, often to the detriment of the fetus. During this 
period many of the symptoms disappear entirely and the 
patient becomes normal, but at the end of lactation she 
relapses and is generally worse than before. The first 
symptoms may appear after one or more pregnancies, if 
the patient's bowels have been regular before and become 
constipated after pregnancy, or if the menstruation be- 
comes abnormal ; it is well to look further for evidence of 
hypothyroidea, especially should the patient who pre- 
viously was active and energetic become languid and 
apathetic regarding her household duties. 



INCOMPLETE MYXEDEMA IN ADULT. 195 

When the disease is fairly advanced the patients become 
somnolent, fatigued, languid and apathetic, everything to 
be done appears to be above their physical and moral 
strength. They complain of feeling unnatural. 

The heart's action is feeble and the second sound accen- 
tuated, or there may be aortic valvular insufficiency, the 
pulse is slower than normal and the temperature may be 
subnormal ; there is often a feeling of depression, which 
appears to the patient to emanate from the cardiac region. 
The erythrocytes are decreased as is the hemoglobin. 
There is often a tendency to hemorrhage, slight injuries 
bleeding freely, epitaxis may occur and postpartem hem- 
orrhage has to be guarded against. These latter symp- 
toms are due to the increased blood pressure and the re- 
duced coagulability of the blood. In the urine there may 
be albumin and casts due to the venous congestion of the 
kidneys. I have rarely found kidney insufficiency in these 
cases, the freezing point of the urine being within normal 
limits, serum albumin and serum globulin are rare though 
nucleoalbumin is not uncommon. The nitrogen elimina- 
tion is low. Byrom Bramwell has noted large quantities 
of mucus in some of his cases. In the urine oxalic acid is 
often in excess, phosphoric acid is low, neutral sulphur is 
high, being often 25 per cent of the total sulphur. Chlo- 
rids are high in proportion to the nitrogen. There is an 
excess of ethereal sulphates, indican and skatoxyl being 
in excess, due to the constipation. The proportions of 
the nitrogen eliminated are pathologic, the urea nitrogen 
may be as low as 65 per cent of the total nitrogen, am- 
monia nitrogen 6 to 7 per cent or even higher. The uric 
acid nitrogen low or normal, the residual nitrogen is often 
very high. The carbon nitrogen factor is usually high; 
urorosein is in excess, bile pigments present in traces and 
sometimes indoxylglycuronic acid. 

The stomach usually shows a hypo- or anachlorhydria. 



196 THE THYROID AND PARATHYBOID GLANDS. 

The latter is rare ; there is an excess of mucus and organic 
acids. 

There are also certain mental changes which may 
amount to insanity, sometimes melancholic, at other times 
maniacal or simply delusional. These cases will be con- 
sidered later. 

The multiplicity and complexity of the symptomatic pic- 
ture calls for the most careful examination by the physi- 
cian, and even then he is often compelled to make a diag- 
nosis by exclusion. 

Treaiment.— The treatment of all forms of myxedema is 
the same, viz : the administration of the thyroid gland of 
some animal, that of the sheep usually being employed. 

Since the discovery of Murray, in 1891, that myxedema 
could be successfully treated by subcutaneous injections of 
an extract of the thyroid gland of the sheep, and the 
further advance of Howitz, of Copenhagen, and Mackenzie 
and Fox, in 1892, that the administration of the thyroid 
by the mouth was equally efficacious the disease is no 
longer looked upon as beyond relief. If the patient is suf- 
fering from abolition of function of the thyroid gland 
alone with no complications thyroid feeding is a specific, 
and no case will fail to be improved or cured by its use. 
There are cases which apparently do not react to thyroid 
treatment in which there is some complicating disease, or 
the disease has produced a dementia from which there is 
no recovery. In other cases the treatment fails from the 
nonabsorption of the drug. The active principle of the 
gland is not absorbed from the stomach, it being only 
soluble in alkaline solutions and is precipitated by organic 
and inorganic acids. Should the intestinal tract of the 
patient be acid throughout its whole length, a condition 
which must be not uncommon in these cases, with whom 
obstinate constipation and intestinal putrefaction, pro- 
ducing fatty acids in quantity, is a constant condition^ 



INCOMPLETE MYXEDEMA IN ADULT. 197 

there would be no absorption of the drug. It is, therefore, 
necessary that in all cases attention should be paid to the 
condition of the digestive tract. The administration of 
natrium bicarbonate in five or ten grain doses and two or 
three grains natrium sulphate in a tumbler of water about 
thirty minutes before meals washes out the stomach, neu- 
tralizes the fatty acids and helps to relieve the constipa- 
tion, the sulphuric acid of the sulphate combining with the 
phenols formed in the colon, rendering them innocuous. 
The desiccated thyroid gland, preferably that manufac- 
tured by Armour & Co., should be given in one grain doses 
three times a day and gradually increased to three grains ; 
it is rarely advisable to go above this dose, though occa- 
sionally five grains is borne without producing symptoms 
of thyroidismus. It should always be administered with 
caution, especially in those cases where the heart is weak, 
or the arteries degenerated, and it should be withdrawn on 
the first symptoms of thyroidismus, commencing again in 
a few days with a smaller dose. 

The addition of a little strychnia and arsenious acid 
have a decidedly beneficial effect. For the constipation 
there is nothing equal to sodium glycocholate mass and 
magnesium oxid. From three to five grains of each will, 
after a week or two, make the bowels act regularly. 

Where the mental depression is severe the addition of 
one grain of opium to each dose of the thyroid will act as 
a heart stimulant. 

In children the dose should never exceed two grains a 
day to commence with, and it is better to begin with one, 
gradually increasing it according to how it is borne. In 
children the alkali treatment is of as much or more impor- 
tance than in the adult ; strychnia and arsenic are useful 
adjuncts in children but the use of opium requires caution. 
The glycocholate of soda and magnesium oxid are not 
adapted for children unless they can swallow a capsule ; the 



198 THE THYBOID AND PAKATHYBOID GLANDS. 

taste of the glycocholate is too nauseous to be adminis- 
tered in solution; liquorice will disguise the taste fairly 
well. 

Should there be dilatation of the heart or if the skin 
symptoms are severe, the Shott baths are a very useful 
adjunct; when given at night they produce refreshing and 
prolonged sleep. 

The diet should be plain and substantial, calculated to 
assist in relieving the constipation. 



CHAPTER XIIL 

BASEDOW'S DISEASE. 

Basedow's disease, exophthalmic goitre, or Graves' dis- 
ease is one of the most interesting of diseases on account 
of the peculiarity of its symptoms and the mystery of its 
etiology and pathology. It was first described in 1835 by 
the celebrated Dublin physician Graves, and in 1840 Base- 
dow gave a complete and elaborate account of its clinical 
features. Since that date the literature on the subject has 
reached enormous proportions, as can be gathered from 
Albert Kocher's monograph on the surgical treatment of 
the disease, which contains no lees than 1423 references. 

Basedow's disease, like myxedema, is much more com- 
mon in women than in men, the proportions varying from 
5 to 10 to^l according to different authors and the age 
from 14 to 60 years, with the majority of cases between 
20 and 40. Unlike myxedema marriage and childbearing 
seem to have little effect in this disease, the preponderance 
of cases occurring in married women, though Byrom 
Bramwell, in his list of 79 cases, found 47 were single and 
26 were married or widows. 

Direct heredity, viz: that the parents had Basedow's 
disease and that it descended directly to the offspring has, 
so far as I can find, never been observed; occasionally 
more than one member of a family is affected. There are 
many cases recorded where the parents or near relatives 
have been affected with some other form of nervous dis- 
ease, or that there is some history of general nervousness, 
hysteria, epilepsy or insanity in some more or less remote 
relation. The weakness of the argument in favor of 
heredity in this and many other diseases, is shown by the 

199 



200 



THE THYBOID AND PAKATHYBOID GLANDS. 



list of cases which Byrom Bramwell cites as evidence of 
the heredity of the disease ; out of 79 cases he finds that in 
one case a sister had a large goitre, in one case an aunt 
had Basedow's disease,- in one case a cousin, two cases 
were sisters, and in another case the patients were sisters. 
In these six cases out of a total of 79 only one case can be 




Fig. 74. — Basedow's disease. 

attributed to heredity and that was from an aunt. Ex- 
haustion from acute illness, especially influenza or loss of 
blood, seems to be an exciting cause. Peripheral irrita- 
tion in the nose and in the abdominal and especially pelvic 
viscera is also an exciting cause ; many cases are on record 
where ovarian or uterine troubles were associated with 
symptoms of Basedow's disease, and that after laparot- 
omy the symptoms disappeared, which may be accounted 



Basedow's disease. 201 

for by the connection of the thyroid with the organs of 
generation. Anemia seems to play a part in the causation 
of the disease. Nervous shock, profound mental anxiety 
and fright seem to have some effect upon its causation, 
though more often a symptom rather than a cause. Many 
of the symptoms and the facial expression are identical 
with those of fright. 

The etiology of Basedow's disease is as yet unsettled. 
Though many theories have been brought forward at vari- 
ous times by different observers none have received gen- 
eral acceptance. Basedow considered that the disease was 
the result of a primary change in the blood, but recent 
investigators have shown that the red corpuscles and the 
hemoglobin are usually normal in amount and when 
anemia occurs it is due to starvation from continued 
vomiting. Stokes was of opinion that the cause of the 
disease was a heart lesion. Lemke attributed it to a 
disease of the muscle of the heart and Askanazy found 
histological changes in the muscle tissue in many cases. 
Jakob claims that these muscle changes are of toxic origin 
but it is more probable they are due to an abnormal meta- 
bolic condition. Disease of the pelvic viscera has from 
time to time been observed associated with this disease, 
the symptoms disappearing after operation on the pelvic 
lesion. Enteroptosis, diseases of the nose, floating kid- 
ney and autointoxication have all had their advocates. 
Benaut described the cirrhosis of the thyroid gland and 
claimed that an imperfect lymph circulation was the cause, 
which was supported by Miiller, who pointed out that the 
lymph glands of the neck are swollen; presumably the 
thyroid was unable to eliminate its colloid into the lym- 
phatics, which would cause swelling of the gland, with pos- 
sibly a change in the colloid substance and also necessi- 
tate its elimination into the blood vessels. Charcot and 
Baschan claimed that the disease was primarily due to 



202 THE THYROID AND PARATHYBOID GLANDS. 

alterations in the ganglion cells of the cortex. Ballet con- 
siders the disease as a bulbar neurosis and von Cyon as a 
lesion of the depressor cordis. 

Several writers agree that the symptoms are the result 
of an irritative lesion of the sympathetic. Pathologists^ 
however, have been unable to find any constant lesion in 
the ganglia either of the neck, thorax or abdomen. There 
being no marked or constant dilatation of the pupils 
argues against the disease being of sympathetic origin ; on 
the other hand, the dilatation of the blood vessels, which is 
a constant condition, may very well be due either to a 
paralysis of the vasoconstrictor or irritation of the vaso- 
dilator fibres of the sympathetic. Pressure on the sympa- 
thetic of the neck by the enlarged gland is also said to 
cause the disease, and some cases have recovered after 
section of the sympathetic of the neck. Frederick sug- 
gested that there might be a paralysis of the vasomotor 
nerves which would cause a dilatation of the coronary 
arteries, thereby increasing the excitability of the cardiac 
ganglia causing increased action of the heart. Lesions in 
the nuclei of the pneumogastric nerve and other structures 
in the medulla oblongata have been found but nothing 
that was not probably secondary in its origin. E. Ze- 
deschi implicates the restiform bodies. He states that 
lesions of the anterior portion of the restiform bodies in 
animals produce marked symptoms of Basedow's disease; 
further that animals in whom the symptoms of Basedow 's 
disease have been induced by lesions of the restiform 
bodies and when such symptoms have been diminished or 
have disappeared they may be reproduced wholly or in 
part by feeding with thyroid to the point of hyperthyroid- 
ism. He further states that lesions of the restiform bodies 
in thyroidectomized animals do not cause symptoms of 
Basedow's disease. In animals in whom the symptoms 
of Basedow's disease have been induced through lesions 



I Basedow's disease. 203 

of the restiform bodies removal of the thyroid diminishes 
or causes the disappearance of the greater part of such 
symptoms. These latter experiments, if confirmed, are 
of great importance. 

Mobius has strongly advocated the theory that the 
primary cause of the disease is hypertrophy and hyper- 
secretion of the thyroid gland. Greenfield and George 
Murray support this view, the latter arguing that the 
gland in Basedow's disease is to be compared to the mam- 
mary gland during lactation. The enlargement of the 
thyroid is one of the chief symptoms and even when com- 
paratively slight there is an increased circulation through 
the gland, producing a hypersecretion which must neces- 
sarily find its way into the circulation. Many of the 
symptoms of Basedow's disease are the exact opposite of 
those of myxedema, which is admittedly the result of 
absence of thyroid secretion ; further, it has been observed 
that Basedow's disease may develop into myxedema on 
the subsidence of the swelling, due to atrophy of the 
gland; while the converse, viz: myxedema developing 
into Basedow's disease has never been recorded and more 
conclusive still is the fact that partial excision of the 
enlarged gland has often been followed by improvement 
and cure of the disease. Edmunds has produced exoph- 
thalmos, tumor, etc., by feeding thyroid to monkeys, and 
cases are on record where the symptoms have developed 
in man from overdosing with thyroid extract. 

In the following table the symptoms of myxedema, 
Basedow's disease and thyroidismus are placed in parallel 
columns, so that the antagonistic symptoms as well as 
those which are common to both can be easily compared : 



204 



THE THYBOID AND PARATHYBOID GLANDS. 



Myxedema, 



Absence or atrophy of the 
thyroid gland. 

Slow, small, regular pulse. 

Torpid, stolid, stupid ex- 
pression. 

Narrowed fissure of the eye- 
lids. 



Slowness of digestion and 
excretion, poor appetite. 

Reduced metabolism. 

Thick, opaque, flabby, dry, 

scaly skin. 
Fingers short and thick, 

often spadelike. 
Drowsiness and somnolence. 

Slowness of perception and 
decreased sensation and 
action. 

Slowness of thought. 



Want of activity and slow- 
ness of motion. 
Stiffness of the extremities. 



Arrested development of the 
bones, short, thick, often 
deformed bones. 

Continuous feeling of cold. 

Slow difficult breathing. 



Increase of body weight. 
Premature aging. 



Electrical resistance of the 

akin diminished. 
Temperature subnormal. 

The bowels constipated. 



Basedow's Disease . > Thjfi'oidistnus. 



DiiTuse swelling of the 
gland, hyper vasculation, 
hyperplasia. 

Rapid, dilated, sometimes 
irregular pulse. 

Anxious, imsteady expres- 
sion; when the gaze is 
fixed fierce expression. 

Widened fissures of the 
eyelids, exophthalmos. 



Abundant excretion, gen- 
erally abnormally large 
appetite. 

Increased metabolism. 

Thin, transparent, injected 
damp skin. 

Long, slender fingers with 
pointed ends. 

Insomnia and disturbed 
sleep. 

Increased sensation, percep- 
tion and action. 



' Rapid, dilated* 
I weak pulse. 



I Widened fis- 
I sures of the 
I eyelids, ex- 
' opthalmos. 
, Abundant ex- 
I cretion. 

I Increased me- 
tabolism. 
Damp skin. 



Nervousness, ir- 
ritability. 



mel- 
and 



Rapidity of thought, 
chical disturbances, 
lucinations, mania, 
ancholia. 

Continuous activity 
rapidity of motion. 

Trembling of the extremi- 
ties, increased motility of 
the joints. 



Slender skeleton, here and 
there soft and thin bones. 

Unbearable feeling of heat. 

Superficial breathing with 
defective inspiratory ex- 
pansion of the chest. 

Decrease of body w^eight. 

Youthful appearance in the 
commencement of the dis- 
ease. 

Electrical resistance of the 
skin increased. 

Temperature normal with 
occasional increase. 

Diarrhea the rule. 



Paralysis of 
one or more 
limbs, mus- 
cular weak- 



Flushings, feel- 
ing of heat. 



Decrease of 
body weight. 



Temperature in- 
creased. 

Diarrhea the 
rule. 



BASEDOW'S DISEASE. 



205 



Myxedema. 

Thyroid feeding cures. 

Skin dry, cold, sweating ab- 
sent. 



Basedow* 8 Disease. 

Thyroid feeding usually in- | 
creases symptoms. | 

Sweatings,* flushings, tre- | 
mors, palpitation, in- | 
creased pulse. i 



! Thyroidismus. 



Characteristic edema of the i 
skin. I 

Loss of the hair of the head 
and eyebrows usually not | 
complete. 

Dryness of the hair, single 
hairs thick and rough. 

Loss of hair rarely complete. 

Pigmentation of the skin 
yellow to brown, seldom 
dark, affects the whole 
body. 

Pigmentation usually most 
marked on eyelids, fore- 
head, face, lips, nose and 
breafits. 

Reduced secretion of saliva. 

geduaad tear secretion rare- 1 

ly increased. 
Want of feeling in the ex 

tremities common. 
Tiredness in the legs. 



A characteristic edema. 

Loss of the hair of the head 
and eyebrows often com- 
plete. 

Hair dry, single hairs thin 
and rough. 

Loss of hair often very ex- 
tensive. 

Pigmentation of the skin 
generally brown, often in 
patches, resembling Ad- I 
dison's disease. | 

Pigmentation usually most 
marked on eyelids, fore- 1 
head, lips, breasts, axillse, | 
region of umbilicus, neck. { 

Reduced secretion of saliva i 
seldom. I 

R e dw s od tear secretion often ' 
increased. i 

Wnnt of feeling in the ex- j 
tremities seldom. ' 

Tiredness mostly very mark- 1 
ed in the legs. / 



Sweatings, 
flushings, tre- 
mors, palpi- 
tation, in- 
creased pulse. 



Hair becomes 
dry and falls 
out. 



The symptoms which are directly opposite, are more 
numerous and more important, while those in which the 
two diseases resemble one another are principally in con- 
nection with the skin. The edema of Basedow's disease 
is, however, hardly the same as the pseudoedema of myx- 
edema. The former is often an irregular condition ap- 
pearing in various parts of the body, rapidly disappear- 
ing, and which is described for want of a better term as 
'* nervous edema." In both diseases there are the lipo- 
matous swellings in the supraclavicular region and else- 
where, but they are by no means so common in Basedow's 
disease as in myxedema. The swelling of the lips and 



206 THE THYBOID AND PABATHYROID GLANDS. 

tongue is apparently the same, but in myxedema it is 
probably due to the pseudoedema, while in Basedow's dis- 
ease it is the result of a congestion. As Basedow's disease 
often passes into a myxedema as the result of the atrophy 
of the thyroid gland those symptoms which are the same 
in both diseases may be really the first symptoms of the 
myxedematous cachexia. The fact that many cases of 
Basedow's disease are improved by the administration of 
thyroidin or phosphoric acid goes to show that in some 
cases there is a pathologic condition of the thyroid secre- 
tion and suggests the possibility that, in spite of the ap- 
parent hypersecretion of the gland, there may be an 
absence of normal secretion producing myxedema, or pos- 
sibly that the gland possessejs a double function, one of 
which may be perverted or lost while the other is increased 
or normal. Recently Ecker, Faure, v. Jaksch, Mackenzie 
and others have observed symptoms of tetany in long 
standing cases of Basedow's disease or after operation. 
It is possible that these symptoms may be the result of 
lesions of the parathyroids. Others again claim that 
Basedow's disease is primarily a disease of the parathy- 
roids and, it is claimed, that good results have been ob- 
tained by parathyroid feeding. It seems not improbable 
that some of the symptoms at least may be due to a path- 
ologic condition of these glands. 

The theory that the hypersecretion of the thyroid gland 
is the principal factor in the production of the symptoms 
of Basedow's disease has been confirmed by the recent 
experiments of Edmunds, detailed in a previous chapter. 
He was able to produce many of the symptoms in mon- 
keys by thyroid feeding, and Notkin reports the case of a 
patient which was diagnosed as a case of Basedow's dis- 
ease, it being subsequently discovered that he had been 
taking enormous quantities of thyroid for obesity. M. 
Gagnevin, a healthy medical student, took full doses of 



Basedow's disease. 207 

thyroid for eight days under the supervision of Dr. Combe, 
of Lausanne, and suffered from palpitation, increased fre- 
quency of heart 's action, tremors, sweatings, flushings and 
exophthalmos. 

ETIOLOGY. 

The arguments against the theory of the hypersecretion 
of the thyroid gland being the cause of Basedow's disease 
are clinical rather than scientific. It is argued that the 
former theory is based upon two postulates. First, that 
the symptoms produced by large doses of thyroid are sim- | 

ilar to the symptoms of Basedow's disease. Second, that | 

the symptoms of myxedema the result of hypothyroidea 
are largely the antitheses of Basedow's disease. 

As to the first point it is argued that an atypical Graves 
disease is not produced by thyroid feeding but only a few | 

symptoms which simulate but are not identical with those j 

of Basedow's disease and that the same symptoms can be' 
produced by the continued administration of other animal 
extracts, especially the parotid, that the symptoms pro- 
duced by thyroid feeding resemble those of overdoses of 
the nitrites and allied drugs. i 

On the second point it is argued that though the symp- ' 

toms of hypothyroidin as seen in myxedema are the op- 
posite of those of Basedow's disease it by no means neces- 
sarily follows that the latter disease is the result of hyper- 
thyroidea and further that there is no other known ex- 
ample of a specific disease due to hypersecretion on the 
part of any gland whatever. Hypersecretion of any gland 
as far as is known is the result of some agent in the blood 
and not of the gland 's self-excitation. In parenchymatous 
goitre a blood poison is undoubtedly present which the 
gland had no share in producing, however much the gland 
may be affected. 

The objections to tlie theory of hypersecretion of the 
thyroid being the cause of Basedow's disease are worthy 



208 THE THYKOID AND PARATHYKOID GLANDS. 

of great consideration, "flie severity of the symptoms of 
Basedow's disease bears no relation to the degree of thy- 
roid hypertrophy which may reasonably be taken as a fair 
index of hyperactivity. The thyroid enlargement differs 
materially from parenchymatous goitre in being variable 
in size and even disappearing with no corresponding 
change in the general symptoms, the size of the thyroid is 
further no indication as to the severity of the disease, and 
that all the symptoms of severe Basedow's disease may 
occur in cases where the thyroid is not palpably enlarged 
as in the so-called masked cases described later. 

From the above it is argued that the enlargement of the 
thyroid is a secondary and not a primary element in the 
etiology of the disease, the result of overstimulation of 
the normal function of the gland or neutralizing certain 
blood poisons generated during digestion in excess. 

The results of feeding in thyroidectomized animals de- 
scribed in a former chapter has led to the conclusion that 
the functipn of the gland is intimately connected with the 
digestive processes and therefore that a marked change in 
the gland or its secretion may be caused by digestive dis- 
turbances. Thompson in his work on Graves' disease 
strongly advocates the digestive etiology of Basedow's 
disease and cites cases of cure or improvement in which 
the treatment has been entirely dietetic with relapses when 
the regimen was neglected. 

In weighing up the etiologic theories of Basedow's dis- 
ease it must be remembered that spontaneous enlargement 
or hypersecretion of the gland is more than improbable, 
that toxemia in some form or another is the cause of nearly 
all disease, that the functions of the thyroid are intimately 
connected with metabolism and assimilation and that the 
chemical evidence of hyperthyroidea being the cause of the 
disease is by no means complete. From the evidence at 
our disposal the etiology of Basedow's disease may be 



Basedow's disease. 209 

summed up to be due to an excessive or perverted secre- 
tion of the thyroid gland, the result of a toxemia probably 
produced in the digestive processes. 

The prognosis in Basedow's disease is a matter of great 
uncertainty. Usually the disease runs a chronic course, 
with intermissions of temporary improvement. In a few 
cases the disease subsides spontaneously, but as a rule the 
cure is far from complete, the symptoms subsiding to a 
certain point and remaining stationary followed by severe 
relapse. Rarely the disease begins suddenly and subsides 
rapidly. In other cases the disease progresses more or 
less slowly, but steadily, terminating in death. In those 
cases where the patient dies from the disease itself and not 
from some intercurrent complication death is gradual but 
occasionally sudden. 

There are five cardinal symptoms of Basedow's disease, 
increased action of the heart, enlargement of the thyroid 
gland, prominence of the eyeballs, tremors, nervous irri- 
tability or a condition of general nervousness, besides 
which the following symptoms may be present: 

Cardinal /&t/twpfom5.— Increased action of the heart, pal- 
pitation, throbbing of the vessels, etc.. 

Enlargement of the thyroid. 

Prominence of the eyeballs. 

General nervousness. 

Fine rhythmical vibratory tremor. 
Digestive Or^raw^.— Diarrhea, 

Vomiting, 

Loss of appetite, bulimia, sudden fits of hunger. 

Thirst, 

Jaundice. 
Respiratory Organs.— Coughj 

Increased frequency of respiration. 

Diminished inspiratory expansion. 
14 



210 THE THTROID AND PABATHYBOID GLANDS. 

Nervous System.— Von Graefe's symptom, 

Stell wag's symptom, 

Defective convergence (Mobius), 

Ophthalmoplegia externa. 

Paralysis, a peculiar form of paraplegia, 

Epileptiform convulsions, chorea, 

Headache, neuralgia, angina pectoris. 

Psychical derangements, depression, mania, etc. 
Integumentary /Sy^fem.— Sweatings, flushings, sensations 
of heat, rises in temperature. 

Diminished electrical resistance. 

Increased pigmentation, 

Leucoderma, 

Loss of hair, atrophy of nails. 
Urinary jSt/5<em.— Polyuria, 

Albuminuria, 

Glycosuria, 

Hyperazoturia, 

Phosphaturia, (?) 

High uric acid. 
Generative St/5<ew.— Menstrual derangements. 

Loss of sexual desire, impotence. 
GeweraZ.— Debility, loss of weight, anemia, cachexia, 
edema of lower extremities. 

Murray and Koeher are very decided in their statements 
that without enlargement of the thyroid gland Basedow's 
disease cannot exist, and in my experience this is true in 
the very great majority of cases. I am, however, con- 
vinced that cases do occur where there is probably a very 
marked hypersecretion of the gland without any palpable 
enlargement; that the enlargement of the gland may be 
posterior or that the hypersecretion may be due to acces- 
sory glands is possible ; the palpation of the gland is ad- 
mittedly attended with difficulty, and any slight enlarge- 



Basedow's disease. 211 

ment may easily escape detection. Byrom Bramwell 
claims that in 10 of his 79 cases thyroid enlargement was 
absent. 

In a typical case the size of the gland may vary from 
being hardly palpable by the practiced diagnostician to 
the size of a goose egg, in which cases the isthmus and the 
pyramid and the accessory glands are also enlarged. 

The enlarged gland is of variable consistence, depend- 
ing upon its vascularity. It is usually firm and elastic if 
the swelling is of some duration. If examined soon after 
its appearance it may be soft and not uniform, some parts 
not being vascular, but firmer and harder than others. It 
is rare that the hyperplastic struma, the common form, 
presses on the trachea sufficiently to produce dyspnea; 
the dyspnea when marked is of cardiac origin. The vas- 
cular struma, or, as Kocher prefers to call it, the telean- 
gretoid struma, is characteristic in its symptoms. 

The circulatory changes in the enlarged gland are usu- 
ally very apparent, the gland pulsates in a manner sug- 
gesting aneurysm, sometimes combined with a lifting 
movement of the whole gland, due to the pulsations of the 
carotids. The gland can be compared to an elastic cap- 
sule filled with enlarged vessels, through which the blood 
stream is passing with abnormal rapidity on account of 
the increased heart's action, producing a marked diastole 
followed by a systole. So great is the dilatation of the 
vessels in severe cases that the arteries can be seen to 
pulsate and the branches of the superior thyroid artery can 
be traced through their tortuous course on the surface 
of the gland by palpation. The veins of the gland some- 
times pulsate, as do also the large vessels of the neck. In 
severe cases the pulsation of the gland veins is a negative 
pulse, due to the dilatation of the vessels, the increased 
circulation and the weakness of the vessel walls. 

On auscultation there is a distinct blowing murmur 



212 



THE THTBOID AND FARATHyBOm GLAXDG- 



present over the gland and vessels, the intensity of whielt 
varieg with the severity of the disease; it is short or loo^ 
and sometimes continaous, systolic in point of time, and 
when continuous is emphasized in systoles. It is best 
heard over the trunk of the arteries^ esi>et-*ialiy in the 
superior thyroid arteries; should the arteria ima or pyra- 
midalis be present the murmur can be heard over them* 
The mummrs are not usually heard over the whole glands 
but only in places ; where vascularitj" is most marked com- 
pression of the gland usually increases the murmur. 

Combined wnth the murmur is another symptom which 
is often present » viz: a friction thrill which can be felt on 
palpation occasionally over the whole gland, but usually 
only in the vascular portions and over the artery where 
the mummr is loudest. Both the murmur and the fric- 
tion sound are due to the rapid circulation and to the swirl 
of the blood stream as it passes from a narrow into a 
wider vessel. 

The vessels are very much enlarged, especially those 
arteriefi which supi:>ly the vascular portion of the struma ; 
if the whole gland is aflfected then all four arteries are 
dilated, as are also the arteria ima and pyramidalis when 
present. Should the hyperemia be reduced the arteries 
will return to the normal size, providing the case is not 
one of too long standing. Hand in hand with the increase 
of the arteries goes an increase in the size of the veins, 
but often not to the same extent, the veins being full and 
only in severe cases dilated- Occasionally when tlie 
struma is compressed, owing to its being extended into 
the upjjer opening of the thorax, the veins of the throat 
and the superficial veins of the breast become dilated, Ib 
long standing cases the jugulars may become dilated. 
The walls of the veins and arteries become thin and weak, 
which cannot be diagnosed clinically, but is a i>oint to be 
remembered during a surgical operation. The micro- 




Basedow's disease. 213 

scopical examination of the walls of the vessels show a 
reduction of the elastic fibres and a space between the 
intima and adventitia. 

Another symptom is that the struma can be partially- 
emptied of blood by pressure, returning to its original size 
as soon as the pressure is removed. It is improbable, ac- 
cording to Kocher, that pressure on the gland causes an 
increased outflow of colloid into the system, which many 
operators consider the cause of occasional sudden fatal 
results from operative procedures. In many cases the 
patients have themselves on several occasions reduced the 
goitre by pressure without any untoward results. 

The etiology of the hypervascularity of the gland and 
the enervation of the vessels must be connected with the 
primary cause of the disease. A vessel nerve degenera- 
tion has been recorded by Guttman and Gerhardt but 
why the nerves of the thyroid vessels should be especially 
attacked is a question which cannot yet be answered. 

The heart fluctuates in size in the majority of cases and 
is dilated in about 30 per cent, depending on the severity 
of the disease. Tachycardia is one of the cardinal and 
most pronounced symptoms of the disease which is always 
present, and may vary from 90 to 250 pulsations per min- 
ute and in some cases is arhythmic ; attacks of angina pec- 
toris are not uncommon; the apex beat is diffuse and 
increased in force ; in severe cases the whole of the car- 
diac area pulsates visibly, the pulsation passing along the 
main arteries producing a marked epigastric pulsation. 
In very severe cases the whole thorax may pulsate while 
the patient is at rest, being so severe as to produce move- 
ment of the head. Palpitation may also be very severe 
but is by no means a constant cause of complaint; it is 
usually the first symptom of which the patient complains 
and is constant, fluctuating in degree, being usually more 
severe in the morning. 



214 



THE XHYKOID AND PAHATHYROID GLANm, 



The heart sounds are accentuated but an abnormality 
can seldom be detected. Murmurs and friction sounds are 
common, varying with the irritation and rapidity of the 
heart, but valvular insufficiencies can rarely be detected. 

As stated above, the pulse is rapid, and throbbing of 
the vessels in the head and neck are often complained of, 
causing great discomfort- The pulse is usually small in 
size and regular; at times it is dicrotic and in the latest 
stages of the disease it may become irregular or intermits 
tent* Besides the murmurs heard over the vessels of the 
neck^ murmurs can occasionally be heard over the smaller 
arteries, as the brachial and crural; there is a distinct 
capillary pulse. Hemorrhage, epistaxis^ bleeding of tlie 
gums, pulmonary hemorrhage may occur- Varicose veins 
and hemorrhoids are common, Becker's retinal pulse and 
Gerhardt's liver and spleen pulsation have been occasion- 
ally obsei'ved. In long standing cases edema of the feet 
and ankles may occur. 

Prominence of the eyeballs, exoplithalmos, which is 
usually bilateral, rarely unilateral, is one of the most 
prominent symptoms, being rarely absent in well marked 
cases. When the exophthalmos is marked and the upper 
lid spasmodically contracted, as sometimes happens, there 
is a typical staring look which gives a fierce or frightened 
expression to the face. So great may be the protrusion of 
the eyeballs that the recti muscles become visible, and 
eases are on record where the eyeball has become dislo- 
cated from the orbit and had to be replaced with the 
finger. The exophthalmos varies according to the emo- 
tional condition of the patient, any excitement causing it 
to increase. A school teacher stated that she first became 
aware of the exophtlialmos by her pupils becoming fright- 
ened by her appearance; this no doubt was partially due 
to the normal retraction of the lid which takes place dur- 
ing excitement. The protrusion may be so great that the 




Basedow's disease. 215 

eyelids are unable to close over the eyeball, producing 
conjunctivitis and ulceration of the cornea, but as a rule 
the eyesight is but little affected, the retinal vessels are 
dilated and occasionally pulsate. Spasm of the fibres of 
Miiller's muscle and the accumulation of fat behind the 
eye in the orbit, with dilatation and engorgement of the 
vessels back of the eye are often given as causes. The 
pupils are usually normal, but may sometimes be dilated, 
they may be unequal ; the absence of any marked change 
in the pupils seems to oppose the theory that the exoph- 
thalmos is due to a lesion of the sympathetic. Stellwag's 
sign is the contraction of the upper lid, which is probably 
due to spasm of Miiller's muscle. The spasmodic con- 
traction of the lid varies in degree and causes the aperture 
between the lids to be wider than normal. This is not a 
constant symptom, but is of importance, though it has 
been observed occasionally in cases where Basedow's dis- 
ease did not exist. Absence of blinking occurs in about 
5 per cent of the cases. Von Graefe's sign consists in the 
upper lid failing to follow the eyeball in a steady coordin- 
ate manner, the lid only following the downward move- 
ment 6f the eyeball in irregular jerks. This symptom can 
be observed by fixing the patient's gaze on an object above 
the level of the eye and slowly lowering the object towards 
the groimd, when the failure of the lid to follow the eye- 
ball can easily be seen. This symptom is present in about 
50 per cent of the cases. Mobius' symptom consists in 
the patient being unable to converge for near objects and 
is present in about 25 per cent of cases. 

One of the most constant and important symptoms is 
the muscular tremor first described by Marie and Charcot, 
consisting of fine rhythmical tremors about eight or nine 
to the second or twice as rapid as the tremors of paralysis 
agitans. The muscles usually affected are those of the 
upper and lower limbs, though occasionally the whole body 



216 THE THYKOID AND PARATHYBOID GLANDS. 

trembles and can be felt by placing the hand upon the 
shoulder. Charcot mentions that the individual digits do 
not tremble, which he claims distinguishes it from the 
tremor of alcoholism and the general paralysis of the 
insane, in which conditions the tremor is equally rapid. 
Occasionally the tremor is unilateral. It can be observed 
best by extending the arm at right angles to the body and 
placing a pencil between the fingers. In a certain pro- 
portion of cases there is an irregular spasmodic jerking 
of the fingers and toes. The tremor usually does not 
appear till the palpitation has become marked; it is a 
symptom of great value in diagnosing cases of masked 
Basedow's disease, which will be described later. 

The nervousness of the patient is a very marked symp- 
tom, contrasting with the apathy and torpor of myxedema. 
There are a number of what may be termed ** simple" 
psychic sjTnptoms, more or less marked, connected with 
Basedow's disease which can be broadly classed under the 
headings of psychic instability and irritability with the 
want of continuity of ideas resembling hysteria or neuras- 
thenia ; occasionally true hysteria or neurasthenia are as- 
sociated with Basedow's disease but the majority of cases 
do not present the stigmata associated with true hysteria 
and neurasthenia and are a part of the symptom complex 
of Basedow's disease. 

Sooner or later after the onset of the disease the char- 
acter of the patient changes, he becomes irritable, selfish, 
peevish, exacting, intolerant of contradiction, never satis- 
fii\l and never recognizing the sacrifices made for him by 
otluM's ; at times he may have periods of most enthusiastic 
Kaioty, changing almost suddenly to bitterness and mel- 
nnoli()li(» doprossion. Generally they have an abnormal 
luMivity, a dosiro to continually change their position, an 
in ilnhility of desire, a fooling of desire, but not knowing 
\N lull it is thov want, tliov are tormented bv an indefinable. 



Basedow's disease. 217 

incessant desire for change ; at one moment taciturn and 
reserved, they almost suddenly become loquacious, speak- 
ing with a singular and apparently forced volubility, sup- 
porting theories contrary to their normal views with 
spasmodic energy, often almost fiercely, forgetting the 
courtesies of argument and at the slightest contradiction 
becoming rude and irate. In time these psychic symp- 
toms which have been happily described as ** psychic 
chorea'' become accentuated, the patient may suddenly 
develop a most marked aversion for some member or 
members of the family without any apparent reason 
which no amount of explanation or argument can over- 
come. More rarely the patient is habitually depressed, 
continually occupied with the contemplation of his own 
troubles he becomes taciturn and morose ; as a rule Trous- 
seau 's description, *Ma maladie de Basedow est une colere 
perpetuelle, " is correct. 

Insomnia and nightmares are almost invariably present, 
adding to the mental and nervous instability ; the memory 
becomes defective in chronic cases, details escape and be- 
come mixed, scientific data and words of a foreign lan- 
guage are the first to be forgotten; in severe cases the 
memory may become so defective that the patient forgets 
what he has read only three or four lines above, making 
reading valueless. 

Will power is as a rule not affected ; it may be dimin- 
ished and very rarely abolished. In most cases, however, 
the patient is changeable, forming different and often con- 
tradictory resolutions at short intervals.. 

These psychic symptoms become mpre and more ac- 
centuated, the patient at times passing the border line and 
becoming insane. Many observers have considered the 
occurrence of insanity in Basedow's disease as a coinci- 
dence, each disease developing separately and from sep- 
arate pathologic conditions, arguing from the insanity 



l\% 



THE THYROID AND PARATHYROrD GLA^'DS. 




being of various kinds— hysteria, epilepsy^ alcoholisin^ 
mania and melaneliolia— whieli progress finally to de- 
mentia. 

The theory of the duality of the disease is not borne out 
by clinical examination; insanity may develop for the 
reason that tlie nervous and mental condition is enfeebled, 
but it is by no means uncommon for the insanity and Base- 
dow *s disease to develop at the same time, the insanity 
subsiding with the other symptoms* In some cases of 
insanity the Basedowic symptoms develop only after some 
time, in which case they may have been latent, uiesked or 
incomplete and have been the primar>* cause of the in- 
sanity, or they have developed independently of the in- 
sanity- 

The form of insanity supervening in Basedow's disease 
is most frequently depressive mania, exaltation rarely 
occurring, melancholia and delusions of persecution re- 
sembling paranoia. In a case diagnosed ajs paranoia 
which came to autopsy the thyroid was found much en- 
larged, weighing 94 grams, though no enlargement had 
been observed during life. 

The insanity of Basedow's disease is attributed by 
Hirschl to changes in the cerebral eireulation (probably 
the cause of all the insanities). Jactjuim considers it due 
to the emaciation imd weakness when the nutrition is poor 
and the continued vomiting and insomnia have weakened 
the nervous system. In his opinion insanity plays the 
same role in Basedow *s disease as delirium in typhoid 
feven Most observers ascribe the mental sym]>toms to 
the diseased eonc^tion and hypersecretion of the thyroid. 

Direct experiment upon the human as to the effect of 
excessive thyroid feeding on mentality is of course impos- 
sible^ but several cases are on record where mental symp- 
toms have been produced by accidental overdosing with 
thyroid. 



Basedow's disease. 219 

Dr. Boinet in the Semaine medicale, 1899, records the 
case of a man suffering from exfoliating general derma- 
titis who took large doses of thyroid, followed by palpita- 
tion, trembling of hands, increase in size of thyroid, with 
psychic symptoms of delusions of persecution and mental 
confusion, which disappeared on the treatment being sus- 
pended. Dr. Ferrarini treated a woman for obesity with 
large doses of thyroid. She developed mental confusion, 
motor disturbances, depression, tremor and increased 
pulse rate; the symptoms disappeared on the suspension 
of the drug. 

Headache is a severe cause of complaint, neuralgia is 
common, the condition as to sleep is variable, migraine, 
angina pectoris, epilepsy and chorea occur as develop- 
ments during the disease. Charcot describes a special 
form of paraplegia which is peculiar to the disease. The 
parlysis is usually incomplete but may be absolute, the 
muscles are placid and atrophied, the reflexes, deep and 
superficial, are abolished, there are no twitchings, sensi- 
bility and electrical reactions are normal and the bladder 
and rectum under control. There is a sudden giving 
away of the legs, due to an unexpected flexion of the knees, 
which is characteristic of the condition. The paraplegia 
is functional and is not permanent; from the fact that 
there are no sensory disturbances it does not appear to 
be typical. 

In a considerable proportion of cases of Basedow's dis- 
ease there is developed a pigmentation of the skin distrib- 
uted in patches or general, the genital organs, the areolae 
of the nipples and around the orbits are usually darkest 
and may be the only places where the discoloration takes 
place. There is a peculiar dirty, dingy, yellowish brown 
appearance of the skin of the face and more or less of the 
whole body. The pigmentation in one form or another 
occurs in about 40 per cent of the cases, and where goitre 



220 THE THYBOID AND PABATHYBOID GLANDS. 

and exophthalmos are absent is of considerable diagnostic 
value. Patches of leucoderma, urticaria, eczema, ery- 
thema and other skin eruptions have been observed in 
about 10 per cent of the cases. 

There Is diminished electrical resistance of the skin, 
which is in marked contrast to the increased resistance in 
myxedema. This diminished resistance is probably due 
to the dilated capillary vessels which keep the epidermis 
bathed in fluid, the consequent sweating keeping the skin 
moist. Wolfenden found that the average electrical re- 
sistance of the normal skin was from 4000 to 5000 ohms, 
while in Basedow's disease he found it as low as 200 and 
in eight cases the highest was only 500 to 700. In alcohol- 
ism and akromegaly there is also a marked decrease in the 
electrical resistance, but not to anything like the extent as 
the above observations indicate. 

The hair falls out and becomes thin in about 20 per 
cent of the cases and atrophic changes occur in the nails 
in a few cases ; both these symptoms are probably due to 
the anemia rather than to the disease itself. 

The respiratory symptoms are a short, deep, nervous 
cough, occurring in about 16 per cent of the cases ; rarely 
a profuse pink watery secretion pours out from the bron- 
chial mucous membrane. Increased frequency of respira- 
tion occurs, due to anemia, cardiac complication or is 
possibly of nervous origin. Bayson's symptom has been 
observed, viz : a diminished expansion of the chest during 
inspiration. Air hunger is common, the result of the 
anemia ; there is also a weakening of the voice in a number 
of cases. 

The lips are sometimes swollen and congested, bleeding 
easily, sometimes with a continuous tremor, which is in- 
creased while speaking ; the tongue is swollen, the papillae 
enlarged and of a bluish color, vibrating tremors are often 
present. There is a great increase in the secretion of the 



Basedow's disease. 221 

saliva in some cases, in others the patients complain of 
dryness in the mouth and throat ; often there is a difficulty 
in swallowing, rarely due to the pressure on the esophagus 
by the goitre but to the swollen condition and dryness of 
the mucous membranes of the mouth, pharynx and esoph- 
agus, which are of a bluish color; the gums are swollen, 
bleeding easily; the teeth are brittle. 

In about 50 per cent of the cases there is vomiting, 
which cannot be ascribed to stomach derangements, as 
the secretions are usually normal or there may be a slight 
hyperchlorhydria. In some cases the vomiting is one of 
the first symptoms of which the patient complains; the 
vomiting may only take place in the morning when the 
stomach is empty, quantities of mucus being ejected 
which may be neutral or very slightly acid ; the vomiting 
is sometimes so severe as to produce starvation, when the 
breath may have the sweet odor of acetone, diacetic acid 
appearing in the urine. It has been suggested that the 
vomiting of pregnancy is the result of the increased secre- 
tion of the thyroid. 

Diarrhea occurs in about 50 per cent of the cases in 
sudden paroxysms without any apparent cause, persisting 
for several days and then disappearing; the evacuations 
are frequent, copious and watery, containing much mucus 
unattended by pain or colic, though in exceptional cases 
there may be colicky pains before an evacuation. There 
is said to be a very large elimination of phosphates in the 
feces. During an attack the tongue is clean and the appe- 
tite good or even voracious. Astringents are usually of 
little value, the diarrhea being of circulatory origin due to 
vaso-dilatation. The diarrhea, like the vomiting, may 
only occur in the morning, and in some cases is followed by 
obstinate constipation. Acholia is occasionally observed. 

Excessive sweating is a very characteristic and constant 
symptom, combined with flushings of the face, hands, feet 



222 



THE THYEOID AKD PASATHYBOID GLAKD8. 




or body with sensations of heat, but distinct rise of tem- 
perature is rare. The flushings and excessive sweating 
without increase of temperature are a valuable diagnostic 
symptom^ occurring in about 90 per cent of all cases. 

Enlargement of the lymphatic glands and spleen has 
been obsei'ved. In this connection it is interesting to note 
the frequency of persistence or regeneration of the thymus 
in this disease. Rendu, Johnstone, Hale White, Mobius, 
Maricj Joflfroy, Schnitzler, Mackenzie and Edmunds, Ga- 
zone and Murray have all pointed out the frequency of 
this condition. Bonnet reports 20 cases in which this 
abnorniality existed, coinciding usually with a hyjTeriilasia 
of the lymphatic tissues. 

Loss of weight is usually a very prominent synii>tom. 
In severe cases not only does the panniculua disappear but 
the muscles are also affected. Very rarely a patient in 
spite of vomiting and nervous irritability will remain in 
good condition, sometimes even gaining in weight. The 
vomiting is probably the result of the increased thyroid 
secretion, as is perhaps also the voiuiting of pregnancy. 
The loss of weight is accompanied by general weakness, 
until the patient is unable to do any work, and finally is 
confined to bed* A paraplegia already described results 
with the typical giving way of the knees. At the com- 
mencement of the disease there is usually a feeling of 
tiredness in the muscles which renders all exertion a 
burden. 

Menstruation is usually decreased^ though occasionally 
it may be profuse but is rarely normal. The maminie 
shrink as the disease progresses but there is not a distinct 
atrophy. 

The urine is usually normal or slightly increased in 
quantity, even when polydipsia is iiresent^ the excess of 
fluid being eliminated by the skin. Glycosuria occurs in 
a few cases and albumin in small amounts is often present. 



Basedow's disease. 223 

sometimes with casts probably of vasomotor origin. The 
urea and nitrogen are much increased, the phosphorus 
elimination is sometimes normal, usually much increased. 
Drechsel found that in patients taking considerable quan- 
tities of sodium phosphate there was no increase of the 
phosphates in the urine, probably they were eliminated in 
the feces ; the uric acid was enormously increased in one 
case. Drechsel found 5.4 grms. in the 24 hours. This 
may be due to the cell destruction. The carbon nitrogen 
factor is low, oxalic acid is often slightly increased, the 
proportion of neutral sulphur is low, chlorids are usually 
low, bile pigment is often present, indol is generally above 
normal. In cases where there is starvation acetone and 
diacetic acid may be present. 

There is a great aggravation of the cardinal symptoms 
immediately preceding death, the mental symptoms de- 
velop into an acute delirium requiring restraint, the tem- 
perature rises to 103° and 104°, the pulse and respiration 
are greatly increased. Vomiting, diarrhea, sweating, der- 
matitis, jaundice and convulsions may occur. The patient 
appears as if the victim of a nerve storm, some centres 
being more aflfected than others. The delirium consists in 
wriggling about the bed and refusing nourishment; severe 
hysterical-like delusions and hallucinations are common; 
rarely is there melancholia, the patient ultimately re- 
lapsing into a state of complete lethargy with rapid, catchy 
breathing. These final symptoms resemble death from 
removal of parathyroids. 

The pathology of the thyroid gland in Basedow's dis- 
ease has been the subject of very careful study by Achard, 
Askanazy, Brissaud, Edmunds, Ehrlich, Famer, Green- 
field, Haemig, Horsley, Joflfroy, Matheson, Mobius, Miiller, 
Renaut and others with variable results. The most com- 
mon form is parenchymatous hyperplasia of the gland, 
accompanied by structural changes and increased cell pro- 



224 THE THYBOID AND PAKATHYBOID GLANDS. 

liferation, with changes of the colloid substance and of the 
stroma. These changes are characteristic of the tumor 
in the majority of cases, but Famer and Haemig describe 
a number of different forms of struma, most of which 
point to a chemical change in the secretion. It has been 
suggested that the colloid substance becomes qualitatively 
the same as the thyroid mucin, which is the sole constitu- 
ent of the gland during fetal life. Ehrlich and Famer 
found the veins and arteries enlarged, also the capillaries 
were dilated and increased in number. Langhans consid- 
ers that there is an increase in the number of follicles in 
nearly every case and that the contents are sometimes in- 
creased, sometimes diminished, there being apparently a 
qualitative change in the composition of the colloid sub- 
stance. The changes in the protoplasm and nuclei of the 
cells are not constant but usually appear to be in the 
nature of a degeneration. He also found an excess of col- 
loid in the lymph and blood vessels as well as in the stroma 
in the majority of cases. In a certain number of cases 
there is a mixed condition of parenchymatous hyperplasia 
and nodular formations. Struma nodosa is rare and when 
it occurs is probably the result of long standing disease. 
In the mixed form the nodules are usually typical, rarely 
developing into cysts, the hyperplasia is usually colloidal, 
seldom parenchymatous. Langhans found in the exam- 
ination of 16 tumors that 8 were of the diffuse colloid 
variety, 6 partially colloidal and part parenchymatous, 2 
wholly parenchymatous; the colloid substance being ap- 
parently normal. There is apparently no definite histo- 
logical lesion of the thyroid in Basedow's disease. Le- 
sions the same as those described above have been found 
in the thyroid glands of patients who exhibited no symp- 
toms of Basedow's disease. 

The question as to the increase, decrease or qualitative 
change of the colloid secretion in the disease is not yet 



Basedow's disease. 



225 




Fig. 



5.— Thyroid gland in Basedow's 
disease. 



settled. Decreased secretion or rather a decreased quan- 
tity of the colloid substance in the gland has been often 
observed. Oswald, in his analyses of glands from cases 
of this disease, found a decreased percentage of iodin, but 
agreed that as the gland was increased in size the total 
be really increased. Far- 
ner's observation that the 
amount of thyroidin might 
stroma, blood and lymph 
vessels contained an ex- 
cessive amount of colloid 
points to an increased elim- 
ination with or without in- 
creased secretion. Haemig 
and Ehrlich are of opinion 
that the substance found 
in the stroma and vessels 
is either not colloid or at 

least not normal colloid, the latter considering that the 
changes in the colloid substance are due to the increased 
vascularity. 

That the tumor is due to increased vascularity there 
can be no doubt; the pulsation, the murmur and above 
all the fact that ligatures of the arteries cutting off the 
blood supply immediately reduces the size of the tumor, 
and that pressure on the gland reduces the size, it filling 
up again on removal of the pressure, place this point be- 
yond question. 

In the vessels themselves there is usually a thickening 
of the intima and a thinking of the media, the veins suf- 
fering in a like manner. 

The lymphatic glands in the neck are usually enlarged 
and also those of the mediastinum, pointing to a patho- 
logical condition of the lymphatic system. 

15 



226 THE THYBOm AND PAKATHYROID GLANDS. 

INCOMPLETE BASEDOW'S DISEASE. 

As there is an incomplete myxedema so there is an 
incomplete Basedow's disease, which is the result of a 
hypersecretion of the thyroid gland and consequent thy- 
roidismus. These cases vary from the typical with all the 
cardinal symptoms to what appears at first sight to be 
simply nervousness. The tremor is nearly always present 
to a more or less marked degree, combined with a pulse 
rate of 90 or above ; the patient usually gives a history of 
having lost weight rapidly, which she ascribes to her ner- 
vous irritability, the least contradiction or annoyance 
throws her into a state of excitement ; fear is usually the 
most marked symptom, which may resemble paranoia or 
delusional insanity. The appetite is poor, amounting in 
some cases to absolute refusal of all food, often accom- 
panied with vomiting of mucus. There may be occasional 
fits of hunger amounting to bulimia, at other times there 
may be great thirst, the so-called nervous diarrhea may 
also occur. Associated with these symptoms are epilep- 
toid convulsions, chorea, headaches, neuralgia and angina 
pectoris. In these atypical cases flushings, which the pa- 
tient calls rushings of blood to the head, excessive sweat- 
ing, and subjective temperature are of diagnostic value. 
The patient often complains of a difficulty in swallowing. 
A dirty, yellowish pigmentation of the skin is often pres- 
ent, being a lighter shade than the bronzing of Addison's 
disease. I have seen a case where the tremors, the ner- 
vousness and the discoloration of the skin in patches 
around the eyes, the nipples and on the back of the hands, 
with slight oon\'ul$ious, were the main symptoms. There 
are also usually irregularities of the menstrual function. 
In malos loss of sexual desire and impotence are common 
oausos of oomi^laint. 

The hair falls out in a considerable number of eases. 

The urinary dorangonunits are jx^ljTiria, albuminuria 



INCOMPLETE BASEDOW'S DISEASE. 



227 



and glycosuria. Diacetic acid may be present where vom- 
iting is severe, owing to starvation. The nitrogen elim- 
ination is increased at least in the earlier stages, being 
markedly more than the amount taken in the food. 

Of the cardinal symptoms of Basedow's disease the 
exophthalmos is usually absent or very slight and the 
enlargement of the thyroid may not be palpable. 




Fig. 70. F,o. 77, 

Masked Basedow's disease with slight exophthalmos. 

The blood pressure is usually normal but there is not 
the rise either in mean or maximum pressure which should 
occur on taking the erect position ; for example, in a case 
in which the diagnosis of atypical Basedow's disease was 
made the blood pressures were : 

Reclining.— Pulse 95, mean p. 101, maximum p. 140 = 
0.726. 

Standing.— Pulse 105, mean p. 95, maximum p. 135 = 
0.703, showing that the vasomotor system was abnormal. 

The diagnosis of these cases has usually to be made by 
exclusion, but the abnormal postural variations in the 



228 THE THYBOID AND PARATHYBOID GLANDS. 

blood pressure, the sweatings, flushings, rapid pulse, dis- 
coloration of the skin, fine tremors and nervous irritabil- 
ity are usually sujficiently marked to enable the physician 
to make a diagnosis. 

Treatment.— The medicinal treatment of Basedow's dis- 
ease has not so far proved very satisfactory, and the opin- 
ion of today is in favor of surgical interference. Many 
cases can, however, be improved and even cured by careful 
attention to details and by the intelligent use of drugs. 

All cases of peripheral irritation should be removed as 
far as possible and excitement of any kind avoided, the 
patient leading a quiet routine life, in which nothing 
should be attempted likely to increase the rapidity of the 
heart's action. When the case is severe the patient should 
remain in bed. The diet should be plain and nutritious, 
stimulants, such as tea, coffee, alcohol or tobacco, should 
be forbidden or reduced to a minimum. It is not wise in 
this or any other disease to absolutely interdict habits 
which are perhaps lifelong. The worry of the unsatisfied 
desire for the stimulants is usually worse for the patient 
than their moderate use. 

The dietetic treatment is strongly advocated by Thomson 
on the etiologic theory of a toxemia. It consists of a milk 
diet, preferably using fermented milks, such as Koumys, 
Matzoon, Zoolak, etc. Poultry, fish, oysters and eggs 
with well baked or perfectly toasted bread are to be used 
in moderation; vegetables, such as asparagus, tomatoes, 
beets, turnips, carrots, spinach, peas and beans, are pro- 
hibited, as well as red meats ; any food which is tasted in 
eructations is to be avoided, a good rule to follow in all 
dietetics. Thomson's medicinal treatment consists prin- 
cipally of intestinal antiseptics, mercury being preferred 
in the form of blue mass pill once or twice a week. I have 
found that one-thirtieth gr. of the bichlorid combined witli 
five grs. sodium glycocholate-mass three times a day after 



INCOMPLETE BASEDOW'S DISEASE. 229 

meals is more effective ; almost invariably it reduces the 
pulse rate, at the same time stimulating the liver. For the 
gastric disturbances he employs resorcin, bichromate of 
potash, bismuth, salol, etc. 

Other drugs, arsenic, quinin, strychnin, digitalis, iron, 
ergot, are all described as being indicated and producing 
amelioration of the symptoms. Probably strophanthus 
and belladonna are the most reliable of the empiric treat- 
ments. On the theory that the secretion of the thyroid 
was chemically altered and that therefore there was a 
hypothyroidea, desiccated thyroid and thyroidin have 
been administered with apparent success in a few in- 
stances, but most observers report, as would be expected, 
that the symptoms were either not affected or were aggra- 
vated under the treatment. Orthophosphate of soda or 
potash, the latter is to be preferred, as it is less likely 
to produce diarrhea, or better still, phosphoric acid in 
full doses, have produced marked benefit in many cases, 
being especially advocated by Professor Kocher of Berne. 
There is some connection between the phosphorus meta- 
bolism and the thyroid secretion. Administration of 
phosphorus seems to restore the balance of the iodin in 
organic combination in the colloid substance, decreasing 
it when too high and increasing it when too low. 

As the physiological action of the suprarenal gland is 
diametrically opposed to that of the thyroid it occurred to 
the writer that it ought to at least relieve the symptoms 
due to the hyperthyroidea, further it had been shown that 
when the thyroidin molecule is saturated with iodin it 
becomes inert. On these principles desiccated suprarenal 
and Lugol 's solution were administered in a very marked 
case in 1898 with complete success; in 1899 Dr. Todd 
treated a case in the same manner with success, since which 
date Dr. E. L. Whitney and others have tried the treat- 
ment in several cases and the majority have done well. 



230 THE THYBOn) AND PARATHYROID GLANDS. 

Occasionally the addition of a little strychnia has mate- 
rially assisted the heart symptoms. This treatment seems 
to give the best results in those cases which occur at pu- 
berty, menstruation or during and after pregnancy, and in 
the atypical cases referred to above phosphoric acid com- 
bined with this treatment has also apparently been of use. 

Electricity has been strongly advocated by M. Vig- 
oroux and others. He recommends that the constant cur- 
rent should be applied to the neck and the interrupted 
current to the precordial region. In using the constant 
current the electrodes should be firmly pressed deep into 
the neck beneath the angle of the jaw at each side for 
about seven minutes or until the skin is slightly red. The 
strength of the Faradic current depends upon the sensa- 
tions of the patient, bearing in mind that they are in a 
nervous and excitable condition. 

In the most severe cases medical treatment fails and 
recourse has to be made to the surgeon. Ligation of the 
thyroid arteries and partial removal of the gland is at- 
tended with considerable success, the mortality being 
about 1 per cent or less. In cases where the exophthalmos 
is the most severe sjTuptom, section of the cervical sympa- 
thetic is said to be followed by good results. 

Some observers have claimed that thymus feeding has 
produced good results in some cases. It seems hardly 
probable, however, that feeding with a gland which should 
have atrophied under normal conditions and which is path- 
ologically persistent in the majority of severe cases should 
produce any good effects. 

Recently attempts have been made to treat Basedow's 
disease by means of a serum but with only very partial 
success. Portis endeavored to produce symptoms similar 
to those which follow removal of the thyroid and para- 
thyroid glands in animals by means of specific cytotoxins 



INCOMPLETE BASEDOW'S DISEASE. 231 

whose action was selective on the thyroid and parathyroid 
cells, producing degeneration and loss of function. Man- 
kovsky and Goutscharukov claim they have made a thyro- 
toxic serum which produced symptoms resembling tetany, 
the thyroid cells showing evidence of degeneration. Man- 
kovsky introduced the thyroid glands of dogs into the peri- 
toneal cavity of cats at fourteen day intervals; after the 
third injection the serum was separated and proved toxic 
to dogs. Goutscharukov used the thyroids of dogs, inject- 
ing them into rams, producing a serum which was thyro- 
toxic. Portis employed emulsions of dogs' thyroids; be- 
ginning with one gland he increased the dose to ten glands 
which he injected into the peritoneal cavity of a goat. He 
claimed that the serum of the injected animal acquired 
certain characteristics. Injected into dogs it produced de- 
pression, convulsions, vomiting, rapid breathing, hemo- 
globinuria and death ; in other cases fever, lachrymation, 
emaciation and progressive loss of weight. The thyroid 
showed absence of colloid substances, desquamation and 
disintegration of the epithelial cells, followed by the de- 
velopment of papillary proliferations ; there were degen- 
erative changes in other organs. Moebius, assuming that 
the blood of thyroidectomized animals would contain cer- 
tain bodies which would normally have been destroyed by 
the thyroid secretion, considered that they might be used 
to neutralize the excess of thyroid secretion in Basedow's 
disease. Lanz employed the milk from thyroidectomized 
goats in several cases with good results. Moebius serum 
was prepared by Merck and used with satisfactory results 
by J. Moebius and Schultes, but Murray was unable to 
obtain any results. 

Dr. Murray of Newcastle-upon-Tyne prepared a serum 
by feeding rabbits on gradually increasing doses of thyroid 
extract, but obtained no definite results. Lepine prepared 



THE THYROID AND PAKATHYROID GLANDS. 

a serum in a similar way by feeding a goat on sheep 
thyroids. 

One or two cases have been reported where parathyroid 
feeding produced good results, but further experiments 
are necessary before definite conclusions can be reached 
on this point. 



CHAPTER XIV. 
THYROID FEEDING IN GENERAL THERAPEUTICS. 

The thyroid has an especial therapeutic action which 
can be utilized to advantage even when there is no defi- 
ciency in the secretion of the gland of the patient. As 
shown in a previous chapter, its administration dilates the 
arteries, reducing the blood pressure, thereby accelerating 
the heart's action and decreasing the work of that organ; 
it also increases metabolism, causing an increased elimina- 
tion of nitrogen as well as of carbon dioxid ; it also acts as 
a diaphoretic by dilatation of the vessels of the skin ; is a 
slight diuretic and increases the oxygen carrying power of 
the blood. Probably its primary actions are the dilatation 
of the vessels and the increased oxidation. 

The use of thyroid as an accessory to other treatments 
is perfectly rational, especially in cases where there is high 
arterial tension with increased mean pressure : the vasodi- 
lators of the Pharmacopeia are too fugitive in their action 
to be of much value except in emergency, but in the thy^ 
roid we have a drug which can be administered for any 
length of time and which is the natural drug, so to speak, 
of the body. 

One point in the physiological action of thyroid and 
in which it acts differently to the nitrites is its effect on 
the capillary circulation. The nitrates appear to dilate the 
arterioles, thereby increasing the heart rate, but they do 
not produce an increased bulk of blood in the peripheral 
circulation. The administration of thyroid appears to 
dilate the capillaries at least of the skin, producing marked 
reddening and diaphoresis; this point is further empha- 
sized by the dry harsh condition of the skin in hypothy- 

233 



THE THYROID AND PABATHTBOH) GLANDS. 

roidea. The thyroid is the only drug in the writer's ex- 
perience which acts as a capillary dilator; the Nauheim 
haths have the same effect, with this advantage, that at 
the same time the pulse rate goes down. 

When the first successes were recorded thyroid was util- 
ized in almost every kind of disease without any attention 
being paid to its indications and limitations; it appeared 
as if the dream of a universal medicine was about to be 
realized. The medical literature of the nineties abounds 
in reports of its successful use in albuminuria, epilepsy, 
diseases of the skin, gout, tuberculosis, the fevers, leprosy, 
etc., but whatever good effects were obtained were due 
either to the cases being atypical myxedema or to the 
beneficial effects of its physiological action, as stated 
above, upon the patient. 

OBEsmr. 

There is a form of obesity which seems to be due to a 
loss of function of the thyroid gland and which shows but 
few symptoms of myxedema. They are generally cases 
where there has been a somewhat sudden increase of 
adipose deposit over the whole body following some acute 
disease, such as typhoid fever, or in women after preg- 
nancy, or when the climacteric has arrived at 35 or 40 years 
of age. These patients will usually complain of rheumatic 
pains in the limbs, which they ascribe to the extra amount 
of weight they have to carry. There are also often ner- 
vous disturbances which may be due to fatty heart, con- 
sisting of giddiness and faintness combined with a nervous 
condition which sinmlates hysteria. Nervous attacks of 
this nature occur at irregular intervals without any appar- 
ent cause, the patient may be domineering and irritable, 
causing family troubles. There are few physical signs 
excej^t the ol>osity which may be confined to the face and 
body, the lower limbs lacing but little larger than normaL 



\ 



GLYCOSURIA. 236 

There is a peculiar change in the contour of the neck, 
which appears square, the anterior central portion failing 
to project. Occasionally the symptoms of myxedema 
may be present in an attenuated form, at other times they 
are entirely absent. 

In these cases great care should be exercised in the ad- 
ministration of the thyroid; on no account should more 
than one grain per day be given at the commencement, 
increasing the quantity very slowly and keeping the pa- 
tient under close observation. It is well to give a little 
arsenious acid and strychnia or adonis vemalis at the same 
time. Very serious accidents may occur from an overdose 
of the thyroid in these cases, owing to the condition of the 
heart and the anemia of bulk which exists in the obese. 
It has been shown that in the moderately obese the total 
weight of blood in circulation may be as low as one-thirty- 
third of the body weight, when it is obvious that any dila- 
tation of the vessels may produce very serious collapse. 
Constipation is often a very troublesome accompaniment 
of obesity, but if the disease is due to thyroid insufficiency 
the first sign that the thyroid treatment is indicated will 
be the regulation of the bowels. 

Thyroid feeding is not an *'antifat" of universal appli- 
cation and should always be given with caution. It is true 
that if large enough doses are given any patient will lose 
flesh, but the heart failure and depression of spirits result- 
ing prevent its use. 

GLYCOSURIA. 

The increased metabolism of carbohydrates and fats pro- 
duced by the administration of thyroid naturally suggested 
its use in glycosuria. At the suggestion of Dr. E. L. 
Whitney it was administered to several patients who had 
sugar in their urine, and where possible, prescribing a 
mild diabetic diet, viz: the patient to abstain from all 



236 THE THYBOm AND PARATHYKOID GLANDS. 

starchy foods and sugars, substituting as much fat, in the 
shape of oil, butter, cream, fat meat, etc., as possible, but 
allowing one slice of toasted bread twice or three times a 
day. It is an easy matter to prescribe a diet but a very 
difficult thing to get a patient to keep to it, but it was 
found that by allowing this small amount of bread the 
patient was able to keep to the diet without much discom- 
fort. There are probably several forms of glycosuria, 
nervous, muscular, hepatic, pancreatic and possibly renal. 
The thyroid treatment could presumably only be indicated 
in the hepatic and muscular forms, while general improve- 
ment of the metabolism might be successful in the nervous 
form. In the pancreatic form, although I have never tried 
it, I should consider it as contraindicated. 

In cases of glycosuria occurring in old age, obesity, as 
well as in some of those occurring in middle life, the above 
diet, coupled with the administration of two grains of 
desiccated thyroid and five grains of sodium glycocholate- 
mass (Hynson & Westcott, Baltimore), to increase the ab- 
sorption of fat and to purge the liver, have brought about 
complete recovery in several cases, so that on returning to 
their ordinary diet there was no return of the glycosuria. 
In other cases in which the diagnosis of hepatic glycosuria 
was made the treatment failed, though in most cases there 
was an improvement in the general condition of the pa- 
tient which was probably due more to the diet than to the 
drugs. 

SENILISM. 

In old age the thyroid atrophies under normal condi- 
tions and although the administration of thyroid wiU not 
restore youth, it will, if given in small doses with some 
stimulant, such as opium or strychnin and arsenious acid, 
improve the action of the heart and dilate the vessels, 
increasing the bulk of the circulation to the various organs. 
In senilism it must be administered with caution, as 



EPILEPSY. 237 

atheroma of the arteries or fatty degeneration of the heart 
muscle may exist. 

BRIGHT ^8 DISEASE. 

In the eariy stages of this disease, when the headaches, 
the dizziness and the dilatation of the left ventricle have 
commenced, all of which symptoms are primarily due to 
increased mean blood pressure, thyroid will often relieve 
the symptoms and arrest the disease in its progress. The 
highest mean blood pressure the writer ever found, 215 
mm. Hg., was in a man of 59 years of age, who complained 
of the most agonizing paroxysms of pains in the head and 
limbs and who had an apex beat to the left of the nipple, a 
slight trace of albumin in his urine with other symptoms 
of early Bright 's. He was relieved by thyroid treatment 
and up to the present the disease does not appear to have 
progressed. Many cases can be relieved and the progress 
of the disease arrested by using the thyroid as a means of 
reducing the blood pressure and attending to the digestive 
organs and the intestinal tract. 

EPILEPSY. 

It would seem that thyroid treatment would be indi- 
cated in epilepsy, as the contraction of the vessels is the 
immediate cause of the spasm, but experience has shown 
that not only does the treatment do no good but is posi- 
tively harmful, increasing the number and severity of the 
spasms. There have been a few cases recorded where the 
administration of thyroid appears to have relieved and 
even cured but they are rare. Parathyroid feeding would 
be presumably indicated from the results of the physio- 
logical experiments detailed in a previous chapter, and 
Dr. Charles G. Hill gave thyroid and parathyroid to an 
idiotic epileptic child in Mount Hope Retreat. The child 
improved in mentality and grew considerably, he also be- 
came clean in his habits, his seizures were less frequent 



238 THE THYBOID AND PARATHYROID GLANDS. 

and much less severe, but whether this latter was due to 
the parathyroids or to his general improvement it is diflS- 
cult to say. In another case of epilepsy in a young man 
the parathyroids were given alone with very great im- 
provement, the seizures being reduced from one or two 
a week to one or two in three months. In a third case 
Dr. Hill reports decided improvement. These results are 
sufficiently satisfactory to call for a further trial of the 
drug. 

MENSTRUAL DISTURBANCES. 

From the connection of the thyroid with the organs of 
generation it is in this field that the most beneficial results 
should be expected ; probably no drug is of so universal a 
benefit in menstrual disorders as the thyroid. At puberty, 
when menstruation is delayed, irregular or scanty, a small 
dose of thyroid daily for a month or two will often bring 
about a normal menstruation with improvement of the 
general health. In young women who suffer from amen- 
orrhea or dysmenorrhea the same treatment is usually 
effective and should always be tried before the patient is 
condemned to a surgical operation. It should be remem- 
bered, in examining these cases, that many of the acute 
diseases of childhood produce a sclerosis and consequent 
loss of function of the thyroid gland, which may render 
it incapable of developing sufficiently at puberty for the 
increased call upon its f unctionation. The thyroid, as was 
stated in the chapter on Physiology, increases in size 
prior to puberty and enlarges at every menstruation as 
well as during pregnancy, and it is therefore evident that 
its funetionation acts as a stimulating cause to the sexual 
proi^esses. In eases of grown women, and especially those 
who have not been married, it often happens, though no 
atrophy of the gland can be detected, that the stimulus of 
an extra amount of thyroid secretion given as desiccated 
thyroid will reestablish menstruation. At the climacteric. 



TETANY. 239 

especially when occurring prematurely, the drug is often 
of benefit, sometimes reestablishing menstruation for a 
time and relieving the various minor symptoms which are 
so common at this period. 

Dr. Charles G. Hill, of Mount Hope Retreat, was the 
first to observe this very important result of thyroid feed- 
ing. He noticed that in some of the chronic insane who 
had not menstruated for a year or two there was a return 
of the flow after one or two months' treatment, invariably 
causing improvement in their physical and mental condi- 
tion. For some reason, which is at present inexplicable, 
the administration of parotid gland is said to have a bene- 
ficial effect upon some cases of dysmenorrhea and is at 
times combined with thyroid treatment. It must be re- 
membered that unlike other emmenagogues which can be 
administered in large doses, producing their effects in a 
day or two, thyroid must be given daily for a month, 
doubling the dose for a day or two before menstruation is 
due, and it may take two or more months before the end 
is attained. In many cases which had been diagnosed as 
retroflexion of the uterus by gynecologists and upon whom 
they had operated without giving relief, a course of thy- 
roid treatment has brought about normal functionation 
and perfect health. 

TETANY. 

Tetany is produced by thyroidectomy and occasionally 
occurs as a symptom in cachexia strumipriva, showing 
that it can be produced by cessation of function of the 
thyroid and parathyroid glands; certain experiments de- 
tailed in a previous chapter seem to point to the latter be- 
ing the etiologic factor. In those cases of cachexia strumi- 
priva which survive the tetanic symptoms may disappear 
for a shorter or longer period, reappearing during preg- 
nancy or some other excitant. 

Tetany is usually associated with disturbances of the 



240 THE THYKOID AND PARATHYBOID GLANDS. 

digestive tract and is probably due to a toxemia ; it has 
also been known to occur as an epidemic. Emotions, 
muscular effort, dentition and rachitis are all given as 
exciting causes. It occasionally occurs in Basedow's dis- 
ease. Infancy, puberty, menstruation, lactation and preg- 
nancy are the periods at which it most commonly occurs. 
The disease has been recorded as associated with gout, 
rheumatism and malaria. 

There are certain forms of epilepsy which have been 
described as ** tetanoid epilepsy," in which there are only 
tonic contractions. The head may be turned, the arms 
extended, elbow joints flexed and fingers flexed, the latter 
in the interosseal position. The spasm may last for a 
longer or shorter time, the muscles affected varying, there 
may be frothing at the mouth and the tongue may be bit- 
ten, the distinctive point being that there are no clonic 
convulsions as in the true epileptic seizure. 

In certain cases in childhood the tetany may be due to 
defective thyroid secretion, cases being on record where 
thyroid treatment has proved effective. The physician 
often never sees the patient during the seizure and has to 
be content with the report of the friends as to the nature 
of the convulsions. Consequently he is unable to make 
the ' distinction between a tetanoid and a true epileptic 
seizure. Though by far the greater number of convul- 
sions in childhood are due to digestive disturbances, it is 
a point worthy of careful investigation, especially if the 
attacks occur at intervals, as to whether the attacks are 
epileptic or tetanic in their nature and in the latter case 
to examine for ix)ssible hypothyroidea. 

The importance of the thyroid during menstruation, 
pregnancy and lactation has been emphasized in preceding 
chapters, and con\nilsions occurring at these periods with- 
out any apparent cause point to thyroid insufficiency. 
Attacks occurring during pregnancy, labor or lactation 



ECLAMPSIA. 241 

are usually termed eclamptic. Recent investigations go 
to prove that eclampsia is due to thyroid insuflSciency in 
a certain number of cases. There are cases where convul- 
sions occur during the latter months of pregnancy as well 
as during labor, which continue at intervals without these 
exciting causes. 

A case occurred in the writer's practice where a mar- 
ried woman had had convulsions during pregnancy and 
labor on three occasions, giving birth to healthy children. 
During the fourth pregnancy and labor no convulsions oc- 
curred ; with the fifth and last pregnancy there were again 
convulsions. On recovery the seizures returned at inter- 
vals, sometimes as often as two or three times per week. 
The convulsion consisted in tonic contractions only, the 
patient being partially conscious during the attack. She 
was treated with large doses of thyroid, as high as 30 grs. 
per diem; the seizures were reduced in number and se- 
verity but after treatment was suspended they gradually 
increased in number and severity, again decreasing on the 
resumption of treatment. 

From experimental and clinical evidence it is probable 
that a certain number of cases of tetany which simulate 
epilepsy are due to thyroid insuflSciency. 

ECLAMPSIA. 

The consensus of opinion at present is that eclamptic 
convulsions are the result of an autointoxication, and that 
the conditions existing are an increased mean blood pres- 
sure, a perverted metabolism, a decreased elimination by 
the kidneys, with, in the majority of cases, albuminuria 
with or without casts, the pathologic findings being fatty 
degeneration of the liver and kidneys. The placenta may 
be looked upon as a digestive organ preparing the nutri- 
tion for the fetus, and possibly it may also have a hepatic 
function destroying the toxic products of fetal metabolism 

16 



242 THE THYROID AND PARATHYROID GLANDS. 

before the fetal blood enters the vena cava; consequently 
a pathologic condition of the placenta might produce 
toxemia in the mother. 

The connection of the thyroid gland with the organs of 
generation has been well established, the gland enlarging 
at puberty and during menstruation, pregnancy and lacta- 
tion. The far-reaching effect of hyposecretion of the gland 
and the various disturbances the condition produces has 
led many investigators to experiment as to the possibility 
of producing eclampsia by partial thyroidectomy. 

In experimenting with thyroidectomy Halstead observed 
that a bitch, who had been deprived of a large portion of 
her thyroid gland but remained in apparently perfect 
health, became impregnated by a normal dog and prog- 
ressed without any signs of hypothyroidea till term, but 
at delivery showed all the symptoms of athyroidea, in- 
cluding convulsions. Since this observation many experi- 
ments have been made on this point, notably those of Ver- 
straeter and Vanderlinden (Ann. de la Soc. de Med. de 
Gand., 1897), v. Eiselberg (Die Krankheiten der Schil- 
druse), I. Jeandelize {Insufjisance thyroidienne et parcu- 
thyroidienne) and Lange (Zeit. f. Geburt. u. Gyn.). 

The latter removed one-fifth of the thyroid gland from 
10 pregnant cats; 2 died in coma, one 23 days and the 
other 38 days after the operation, 3 had convulsions 23 
and 25 days after operation. Three of these cases had 
albuminuria and at autopsy fatty degeueration of the liver 
and kidneys was found. The other five cats remained well, 
but at autopsy three of them were found to have the same 
pathologic lesions. Lange also examined a series of 133 
cases of pregnancy and found that the hypertrophy of the 
thyroid commenced in the fifth month in multiparas and 
in the sixth month in primiparas; he also found on the 
administration of small doses of thyroid to pregnant 
women with enlarged thyroids that the gland returned to 



ECLAMPSIA. 243 

• 

normal size, but on the cessation of the treatment it again 
hypertrophied. Of the 133 cases examined he found the 
gland enlarged in 108 cases, 3 were doubtful, in 22 there 
was no enlargement, of the 22 twenty showed albuminuria, 
16 albuminuria with casts, 6 of these cases developed 
eclampsia ; of the 108 with hypertrophied gland only two 
had albuminuria and one of these was a nephritic ; none of 
the 108 developed eclampsia. 

Herrgott reports a case of incomplete myxedema where 
eclampsia developed. Verstraeter, Vanderlinden and 
Nicholson (The Scot Med. and Surg. Jour., 1901) report 
cases of eclampsia, which they attribute to thyroid insuf- 
ficiency, the latter treating a case with thyroid with suc- 
cess. 

The thyroid function being increased during pregnancy 
it is evident that if for any reason the thyroid has failed 
to fully develop, though secreting sufficient under ordinary 
conditions, it will fail to respond to the excessive demand 
upon it during pregnancy. It is by no means uncommon 
for the thyroid to be affected by the acute diseases of 
childhood, rheumatism, typhoid, etc., as has been shown 
by Gamier and Roger ; consequently at the first pregnancy 
there is a deficiency of thyroid secretion which may be a 
factor in producing eclamptic convulsions at term in pri- 
miparas. The excitation of the gland during pregnancy, 
will have a tendency to increase its functionation, prevent- 
ing the recurrence of the symptoms at the next pregnancy. 
In other cases the gland never acquires a sufficient secret- 
ing power and eclamptic convulsions occur at every suc- 
cessive labor. In those who have no eclamptic symptoms 
at the first pregnancy, but in whom they appear in the 
later pregnancies, it may be assumed that the strain upon 
the gland during the first pregnancy or some intercurrent 
disease has affected the functionation of the gland. 

The principal symptoms of eclampsia are the same as 



244 THE THYKOID AND PARATHYBOID GLANDS. 

• 

those t)f hypothyroidea, viz : high mean arterial pressure, 
decreased elimination by the kidneys, perverted metabo- 
lism and very often albumin and easts. In partially thy- 
roidectomized animals the same symptoms occur while the 
principal pathologic lesion is fatty degeneration of the 
liver and kidneys. From the above data it is probable 
that a certain number of cases of eclampsia are due to a 
hyposecretion of the thyroid and parathyroid glands. 

The following case occurred in the practice of Dr. 
Charles G.Hill: 

A primipara was examined six weeks before term. Her 
24 hours' urine was found to contain 11.37 grms. albumin, 
with some casts, the nitrogen occurring as urea, 79-8 per 
cent; ammonia N, 9.2 per cent; uric acid N, 1.8 per cent; 
residual, 9.2 per cent; chlorids, 10.4; phosphoric acid, 
PA, 2.65: 

carbon G.16 

=0.77. 

nitrogen 7.98 

The blood pressure showed a very high mean in proportion 
to the maximum 

mean 1G8 mm. 'Hg, 

=0.8, 

max. 208 mm. Hg. 

with a pulse of 105. Dr. Hill, who had attended her be- 
fore marriage, had diagnosed hypothyroidea when she had 
improved under thyroid treatment. He gave her full 
doses of thyroid and parathyroid, the blood pressure fall- 
ing under the treatment to 

mean 152 mm. Hg. 

=0.76; 



max. 198 mm. Hg. 

pulse, 95 ; the relation of maximum pressure to mean pres- 
sure being nearly normal. She was delivered two weeks 
before term without any accident. The day after delivery 
the blood pressures were 



IMPOTENCE. 2-15 

mean 140 mra. Hg. 



max. 182 mm. Hg. 



= 0.7 



or normal. Nineteen days after delivery albumin was 
absent from the urine; urea N, 83.7 per cent; ammonia N, 
8.0 per cent ; uric acid N, 0.55 per cent ; residual N, 7.75 
per cent, being normal except for the still high proportion 
of ammonia N : 

carbon 4.56 

=1.0; 

nitrogen 4.48 

chlorid, 6.4; phosphoric acid, P2O5, 1.68. The thyroid 
treatment was discontinued at the time of delivery, but 
commenced again on the fourth day, as the urine became 
scanty, the pulse hard and lactation had not commenced.' 
In a day or two the lactation was normal, the patient 
making an uninterrupted recovery. 

IMPOTENCE. 

Impotence in man and frigidity in woman are conditions 
which are occasionally benefited by thyroid treatment. In 
man when the want of sexual power is due to a non- 
development of the penis, as shown by the small size of 
the organ with an elongated prepuce covering the glans 
which is with difficulty withdrawn, and when the testicles 
are small and soft to the touch, the scrotum without the 
pigmentation and the rugsB of the normal adult, combined 
with a history of congenital want of power and possibly 
also of desire, a course of thyroid feeding, extending over 
several months, will sometimes produce a marked develop- 
ment of the penis, the prepuce withdrawing from the glans, 
the testicles enlarging and becoming firm to the touch 
and the scrotum normal in appearance. The desire and 
capability for the sexual act may become normal and even 
excessive. I have often observed among the insane that 
patients under thyroid treatment became intensely erotic. 



246 THE THYKOID AND PARATHYROID GLAND3. 

mapturbating continually. This is more often observed in 
females. Occasionally the treatment had to be suspended 
owing to the sexual excitement it produced. If the im- 
potence is due to pollutions or spermatorrhea or any 
derangement of the circulation of the organs, thyroid 
treatment is, of course, useless, but in those cases where 
there is no apparent cause and especially when the patient 
is obese the treatment is often successful. In the female 
it is difficult to diagnose arrested development of the 
sexual organs, but should there be a history of delayed 
menstruation with a tendency to masculinism the treat- 
ment will often increase the sexual desire. 

In cryptorchidia, either unilateral or bilateral, thyroid 
feeding will sometimes cause the descent of the testes. 

It is obvious that this treatment is only indicated in 
isolated cases where there is evidence of arrested develop- 
ment of the organs or loss of thyroid function. A female 
patient,, who was under thyroid treatment for amenorrhea 
and delusions, complained of almost uncontrollable sexual 
desire after the menstruation had been established and the 
delusions had disappeared. 

From the connection of the thyroid with the sexual 
organs, its increase in size at puberty, during menstrua- 
tion and pregnancy, as well as from the fact that in cretin- 
ism and infantilism the genitalia do not develop and 
puberty is either never established or delayed for it may 
be years, it is surprising that more cases of impotence in 
the male and frigidity in the female are not benefited by 
thyroid treatment. 

NERVOUS DISEASES. 

As has already been stated the action of the thyroid is 
alterative. By dilating the vessels it brings an increased 
blood supply to the organs and tissues of the body and 
consequently may and does act beneficially in many dis- 



DISEASES OF THE SKIN. 247 

eases. In most cases where there is an increased iqean 
blood pressure thyroid medication will do good, provided 
it is not pushed so far as to produce thyroidismus or men- 
tal depression from its effect upon the heart. In some of 
these unclassified conditions which are grouped in the 
conglomeration of ** functional neuroses'' it will be found 
on careful examination that there are symptoms of incom- 
plete or marked myxedema, while in others the increased 
mean pressure is an indication for thyroid treatment. 

PARALYSIS AGiTANs— Parkinson's disease. 

This disease is ascribed to exogenous toxemia from al- 
cohol, lead, mercury, etc., but variability and the absence 
of nerve lesions seems to point to some constitutional de- 
fect or to autotoxemia. Castelloi considers that autoin- 
toxication is the etiologic factor. The tremblings, sensa- 
tions of heat and other symptoms common in this disease 
also occur in exophthalmic goitre, which led him to think 
that the thyroid might be implicated. In two post-mor- 
tems he found in the first that the thyroid only weighed 
145 grains and in the second the gland was cystic. He 
also claims to have had good results from thyroid feeding. 

DISEASES OP THE SKIN. 

Thyroid treatment has been found to be of benefit in 
many cases of skin disease, notably psoriasis, due no doubt 
to the increased circulation in the skin. It will be remem- 
bered that one of the most marked symptoms of myxedema 
is connected with the skin, the pseudoedema and the dry, 
scaly, harsh condition, with the absence of^ perspiration 
and secretion of the sebaceous glands show that the circu- 
lation is decreased. It is probable that the benefit derived 
in skin diseases from thyroid treatment is due to the in- 
creased circulation to the parts. * 



248 THE THYROID AND PABATHYBOID GLANDS. 

ADIPOSIS DOLOROSA. 

Of this rare disease only five eases have yet come to 
autopsy, four having been reported by Dr. F. X. Dercum 
and one by Dr. Burr. In two, gross disease of the thyroid 
was found, the glands being the seat of calcareous deposit; 
in the third there was irregular atrophy of the thyroid 
gland with efforts at compensatory hypertrophy; in the 
fourth there were the same changes in the thyroid with 
enlargement and gliomatous degeneration of the pituitary 
body. In the fifth case the changes in the thyroid were 
slight, but there was adenocarcinoma of the protuberance 
of the pituitary body and hemolymph glands. The rela- 
tion of the thyroid to this disease seems to be established, 
but is probably combined with diseases of the pituitary 
body. Thyroid treatment does not seem to have amelior- 
ated the symptoms. 

In akromegaJy there seems to be some derangement of 
the thyroid gland, but up to the present the etiology of the 
disease is unknown. 

HEMORRHAGE. 

In certain cases of persistent hemorrhage the adminis- 
tration of thyroid extract in 5 gr. doses with the addition 
of calcium chlorid will increase the coagulative power of 
the blood. Dr. Bloodgood reports cases where he found 
this treatment effective when other methods of arresting 
bleeding had failed. 

MENTAL DISEASES. 

The use of the thyroid in insanity dates from 1892, 
when it was used in the Morningside Asylum in Edin- 
burgh with very good results, since which time it has been 
used with varying success by different specialists. There 
has been unfortunately an idea prevalent that the treat- 
ment was applicable to all forms of insanity and it has 



MENTAL DISEASES. 249 

been used without discrimination, no attention being paid 
to the symptomatic indications for its use. Several spe- 
cialists have given it to a large number of cases and, re- 
porting improvement or cure in about 5 per cent of the 
cases, were disappointed at the result. Easterbrook finds 
it of benefit in about 9 per cent of all cases, but disease of 
the thyroid gland is said to be more prevalent in Scotland 
than in this country. In the experience gained at Mount 
Hope Eetreat I am of opinion that about 5 per cent of all 
cases are improved by the drug and in many of these it is 
only as an accessory to other treatment that it is of benefit. 

The number of insane patients suffering from myx- 
edema, even in an atypical form, is probably very small 
and, as the mental disturbances may assume the form of 
dementia, melancholia, or mania, the psychic disturbances 
are no guide to the therapeutic use of thyroid. It is very 
rare that it is of any use in the acute stages of the disease 
and has the objection of decreasing the appetite, some- 
times producing absolute refusal of food, and further a 
drug which increases metabolism and elimination of both 
nitrogen and carbon must be contraindicated when there 
is poor assimilation and the system run down. Before 
commencing to administer thyroid the digestive organs 
should be got into a healthy condition and it is a good 
rule not to give thyroid unless the nitrogen elimination is 
at least 8 to 10 grms. in the 24 hours. In cases of true 
myxedema this does not apply, as often in these cases the 
nitrogen is as low as 5 grms. and rises, the appetite im- 
proving at the same time on the administration of thyroid. 

The indications for thyroid treatment are the same in 
insanity as in other diseases, the condition of the circula- 
tion being the principal guide. In cases of acute mania, 
where the mean and maximum blood pressure are low, the 
heart action weak and the patient suffering from anemia 
of bulk, it is strongly contraindicated and may produce 



250 THE THYROID AND PARATHYROID GLANDS. 

Serious results. On the other hand, in cases where the 
pulse is full, strong and rapid, the mean and maximum 
pressure high, the nitrogen elimination 15 grms. or even 
more, with a good appetite and hyperehlorhydria of the 
stomach, thyroid combined with opium will often produce 
very good results, the thyroid counteracting the contrac- 
tion of the abdominal vessels and heart stimulation of the 
opium. 

When there is marked venous stasis, pointing to insuf- 
ficiency of the right heart, and where the mean pressure is 
normal or little above normal, and the maximum pressure 
low, thyroid is contraindicated, as it will increase the 
amount of blood on the venous side of the circulation by 
dilating the arterioles ; on the contrary, if there is a dilata- 
tion of the left side of the heart, with high mean pressure 
and either normal or low maximum pressure, digitalis, 
strychnin or adonis vernalis should be added to thyroid 
feeding. In melancholia, when the mean blood pressure 
is often very high, thyroid is a valuable accessory to the 
opium treatment. 

When the acute stage of the disease is past, the diges- 
tion and appetite improved and the elimination suflScient, 
thyroid in small doses is very useful, increasing the 
amount of the circulation and consequently the nutrition 
of the organs, patients often gaining weight during its use. 

Puerperal insanity is probably the most uniformly bene- 
fited, the reason being that the thyroid has suffered from 
hypersecretion during pregnancy and is suffering from 
cell fatigue, but hypothyroidea is certainly not the cause 
of puerperal insanity or at least only in very rare cases. 

It would seem probable that the thyroid would act as 
an hypnotic from its action upon the blood vessels, re- 
ducing the bulk of blood passing through the brain ; in the 
ordinary sense, viz : that a dose at bedtime will produce 
sleep, it certainly is neither a hypnotic nor an anodyne. 



MENTAL DISEASES. 251 

but often the addition of a small dose of thyroid to the 
daily medicine will in a few days render the use of a hyp- 
notic unnecessary. Here again the indications for its use 
must be looked for. 

There are some cases of delusional insanity which seem 
to be entirely due to thyroid insufficiency; for example, a 
young woman of about 28 years of age, in the practice 
of Dr. MacCalman, complained of visions of ** seeing the 
dead'' at night. This delusion occurred once or twice a 
month and was so vivid that she would scream and run to 
another room for protection, leaving her in a very nervous 
condition. She could give no very clear account of any 
disease before puberty, but stated that she had not men- 
struated until her twentieth year, having had scanty and 
at times painful periods all her life. Her hair fell out at 
irregular intervals, her mean pressure was high ; her thy- 
roid gland could be palpated and was evidently enlarged, 
feeling hard to the touch. On these symptoms she was ' 
prescribed thyroid. During the first month of treatment 
she had one vision, her menstruation was free and normal 
and she had no more visions for some time while taking 
six grains a day. She stopped the treatment and the 
visions returned, disappearing again on resuming treat- 
ment. 

In the administration of thyroid there are several points 
which are of great importance: the initial dose should 
nearly always be small, one grain three times a day is, as 
a rule, safe and can be gradually increased, but it is very 
rarely necessary to go above two grains. Another point 
is the condition of the digestive tract, as thyroglobulin is 
precipitated by organic and inorganic acids, it is impor- 
tant that alkalis should be administered at the same time, 
as should the intestines contain large quantities of organic 
acids, a by no means uncommon condition, the drug will 
be only partially absorbed. The condition of the heart 



252 THE THYROID AND PABATHYROID GLANDS. 

requires watching, as an overdose may produce serious 
results and very great depression of spirits ; especial care 
is required in old people where atheromatous arteries and 
fatty heart may exist. Of the drugs which are advan- 
tageously combined with the thyroid arsenious acid is 
generally indicated and appears to aid the treatment. 
Strychnia, digitalis and adonis vernalis, especially the lat- 
ter, are of benefit when the heart is weak and the dilata- 
tion marked. Opium in nervous diseases gives better re- 
sults in many cases when combined with thyroid, the latter 
counteracting the tendency of the opium to contract the 
arterioles. 

Thyroid treatment is no universal panacea for every ill 
that flesh is heir to, but bearing in mind its physiologic 
action and seeking for the indications for its use it is un- 
doubtedly a valuable therapeutic aid. 

THE THYROro DURING FETAL LIFE. 

In the sixth week of intrauterine life the organs of the 
thorax and upper part of the abdomen may be said to 
have completed their development; that is to say, they 
grow during the remaining 34 weeks but show no changes 
in construction till birth forces new functions upon them. 
At this period the development of the thymus from the 
entoderm of the third gill cleft has begun, the two lateral 
anlages of the thyroid unite with the single median anlage 
at the seventh week, the ductus thyroglossus may remain 
open till the eighth week while hollow acini have com- 
menced to form. 

At birth the isthmus of the thyroid gland lies in front of 
the trachea, opposite the body of the fifth and sixth verte- 
brae; with the head flexed it is in contact with the upper 
border of thymus, its lateral lobes extending from the 
lower border of the thyroid cartilage to the level of the 
fourth or fifth tracheal ring. The weight of the gland is 



THE THYROID DURING FETAL LIFE. 253 

given by Ballentyne as 7 grms. The writer has found the 
average weight in two stillborn children at term to be only 
1.4 grms. ; other writers place the average weight at about 
2 grms. 

The thyroid is known to be the great regulator of body 
metabolism and to be essential for growth ; in at ajiy rate 
the early years of life defects in it are the cause of cretin- 
ism and infantilism, diminished thyroid activity leading 
to a decrease of the nutritive processes. The thyroid 
function is increased during pregnancy and also during 
lactation, the marked flow of milk on the third day of the 
puerperium is due to the increase of the thyroid secretion 
in the maternal blood caused by the birth of the fetus. 
Experimentally it has been shown as stated in a previous 
chapter, that the administration of thyroid increases the 
secretion of milk. The question arises,Has the thyroid of 
the fetus the same regulating fimction in connection with 
the metabolism of antenatal life as the thyroid of the 
mother over adult life, or has the thyroid of the mother 
the double function of regulating both the maternal and 
the fetal metabolic processes! It has been shown by ex- 
periment, as stated in a previous chapter, that if the thy- 
roid of the mother be removed there is apparently a com- 
pensating hypertrophy of the thyroid of the fetus ; it has 
further been shown that the fetal thyroid contains no 
iodin and in a number of cases that I have examined of 
stillborn children at term and also of children who have 
lived a few weeks that there is no iodin in the gland. The 
fetal gland contains thyromucin, but it does not contain 
the substance which quickens the pulse and lowers the 
blood pressure. Whatever may be the function of the 
fetal thyroid during fetal life it is evident that it is from 
the maternal gland that the fetus receives the active 
principle, and further that as the child at birth and for 
some time after has no thyroidin in the thyroid it must 



254 



THE THYBOID AND PABATHYBOID GLANDS. 



receive the amount which it requires from the mother 
through the milk. In the cow it is otherwise; the gland 
of the fetal calf contains iodin as well as the substance 
which increases the pulse rate and reduces the blood pres- 
sure. It seems probable that under these circumstances 
that cow's milk will not contain any thyroidin while hu- 
man milk will contain it. 

It seems possible that the difficulty of rearing infants 
on artificial food may be due to the absence of thyroidin 
in the cow's milk. 

Quantitative analyses of the thyroids for iodin and 
thyroglobulin were made of six children dying of inani- 
tion. In no case was any iodin found in the gland and 
the amount of thyroglobulin estimated by Oswald's method 
gave the following results : 



Childrb 


N Dying of Inanition. 




Normal Children 




Veightqf 


Thyroglob- 




Weight 0/ 


ThoroffMh 




Tiyroid. 


idin. 


Iodin, 


Thyroid. 


ulin. 


Iodin, 


1.4 


0.0912 


absent 


1.9 


0.4686 


trace 


1.4 


0.0882 


it 




(2 yrs. old) 




0.64 


0.0574 


t( 


1.3 


0.1083 


absent 


0.9 


0.084 


it 




(stillborn) 




1.45 


0.089 


(t 


1.4 


0.1029 


€t 


0.7 


0.035 


it 




(stillborn) 





The above analyses show that in children dying of inani- 
tion the weight of the thyroid is but slightly lower than in 
stillborn children, while the thyroglobulin is less, and that 
iodin is absent both in the inanition cases and in stillborn 
children. 



BIBLIOGRAPHY. 



Owing to the very large amount of literature on the subject of the 
thyroid and parathyroid glands only articles published since 1900 are 
indexed; for earlier publications the reader is referred to the Catalogue 
of the Surgeon-General's Library, Washington, D. C. 

Achar (G.) : XIII Congr^s Internat. de M6d., Paris, 1900. 

Apert (E.): Bulletin Medical, 1901. Arch, de M^. des Enfants, 1902. 

Bulletin de la Soc. de Pediatric de Paris, 1901. C. R. de la Soci6t6 

de Biologic, Paris, 1902. Annales de M6decine et Chirurgie Infan- 

tiles, 1902. 
Actualities M6dec.. 1902. 

Ausset (E.) : Congrfes P^riodique de Gyn., d'Obstet. et de Pediatric, 1901. 
Azoulay (L.) : Presse M6dicale, 1900. 
Baldi: II Morgagni, 1900. 
Baldoni: R. Accademia M^. di Roma, 1900. 
Ball (V.) : Soc. de Biol., 1902. 
Bassal: Th^se, Toulouse, 1900-1901. 
Belfrage: Hygeia, 1900. 

Bertarelli: Gazz. degli Osped., 1900. Revue Gen. de Path. Interne, 1901. 
Bezy: XIII Congrfes Internat. de M6d., Paris, 1900. 
Blum: Die schildriise ale entgiftendes organ, 1899. Virchow's Archiv, 

clviii. Jour, de physiol. et pathol. g^n., 1900. 
Blumreich et Zunte: Arch. f. gyn., 1902. 
Bourcet (P.) : Th^se, Paris, 1900. 

Boumeville: Traits de M^decine et de Therapeutique, 1902. 
Bourneville et I^aurens: Progrfes Miklical, 1901. 
Braoud6 (Mile. Nehama) : Th^se, Paris, 1901. 
Breton: Thfese, Lille. 1901-1902. 
Briquet: Presse MMicale. 1902. 
Callari: Gazzetta degli Ospedali e delle Cliniche, 1901. Riforma Medica, 

1901. 
Cao: Jour, des Maladies Cutan^s Syphilitiques, 1900. Riforma Medica, 

1900. 
Cardile et Fiorentini: R. Accad. Peloritana di Messina, 1900. 
Carrel : Gaz. des Hdpitaux, 1900. 
Carrel-Billard : Th^se. Lyon, 1900. 
Caseli: Rivista Sperimentalc di Freniatria e Med. Leg. d Alien, 1000. 

Lyon M^ical, 1900. 
Cecca: Soc. Medico-Chirurg. de Boulogne, 1902. 
Chantemesse et Podwyssotsky : Les Processus G^n^raux, 1901. 
Charrin et Bourcet: Soc. de Biol., 1900. 
Chatin et Guinard: Lyon M^ical 1900. 

255 



256 THE THYBOID AND PAKATHYBOID GLANDS. 

Chepault: Soc. de Pediatric, 1902. Gaz. Hebd. de M^. et de Chirurgie, 

1902. 
Cristiani: Soc. de Biol., 1900. Progrta M6dical, 1901. 
Cyon (do) : Rev. G^n. des rc. Pures et Appliques, 1901. 
Dalch4: Bulletin de la Soc. M6d. des HOpitaux de Paris, 1901. Soc. M4d. 

des HCpitaux, 1901. Sem. M6d., 1901. 
Debovc: Presse M^dicale, 1901. 
Dezon: Revue Hebdomadaire de Laryngologie, d'Otologie et de Rhinologie, 

1901. 
Duprd et Guillain: Bullet, de la Soc. M^., des HOpitaux, 1900. 
Easterbrook: The Scot. Med. and Surg. Jour., 1901. 
Ferrannini: Congr^s de la Soc. Ital. de M6d. Interne, Rome, 1901. 
Fraissex: Th^se, Paris, 1900. 
Fruhinsholz et Jeandelize: Presse M4dicale. 1002. 
Gamier: Province MMicale, 1900. 

Gautier (A.) : Acad, de M^., 1900. Bull. Acad, de MM., 1900. 
Gautier (Ch.) : Thfese, Lyon, 1900. 
Gley: British Med. Jour., 1901. 
Glynn: Liverpool Med. Soc, 1900. 
Hallion: Arch. G<?n. de M6d., 1901. 
Haushalter et Gu<^rin: Revue Mensuelle des Maladies de TEnfance, 1902. 

Soc. de MM. de Nancy, 1902. Rev. M6d. de PEst., 1902. Soc. de 

Biol., 1902. 
Herrgott: Soc. MM. de Nancy, 1902. Rev. MM. de I'Est., 1902. 
Hertoghe: Nouvclle Iconographie de la Saltp^trifere, 1900. 
Hutinel: Gaz. Heb. de Med. et de Chirur., 1902. 
Jacquemet: Th^se, Montpellier, 1900. 
Joachimstal : Deutsche med. Woch., 1900. 
Kashiwamura: Arch. f. pathol. Anat. u. Physiol., 1901. 
Katzenstein: Deutsche inM. Woch., 1900. 
Krafft Ebing: Bolletino delle Cliniche, 1900. 
Lannois: Nouvelle Iconographie de la Saltp^trifere, 1900-1901. 
Leblanc: Soc. de Biol., 1902. 
Lusena: Riforma MMica, 1900. 
Marie: Soc. MM. des HOp., 1902. Sem. MM., 1902. 
Mayet (L.) : Lyon MMical, 1900. Arch. General de MM., 1900. Bull. 

et M4m. de la Soc. d' Anthropologic de Paris, 1901. 
Meige et Allard: Soc. de Neurol, de Paris, 1900. 
Murray: Diseases of the Thyroid Gland, 1902. 
NichoLson: The Scot. Med. and Surg. Jour., 1901. 
Patel: Gaz. Hebd. de MM. et de Chir., 1901. 
Peckranz: Neurol. Centrallbl. Biol., 1899. 
Pollosson et Genevet: Lyon MM., 1901. 
Ponfick: Deutsche med. Woch., 1900. 
Porges: Berl. klin. Woch., 1900. 
Pornain: Progrfes MMical, 1900. 
Quincke: Deutsche med. Woch., 1900. 
Richardi^^re : Soc. de Pediatric, 1902. 
Rivifere: Lyon MM., 1900-1901. 
Roger et Gamier: Presse MMicale. Soc. de Biol., 1901. 



BIBLIOGRAPHY. 257 

Roux et Vitaut: Revue Neurol., 1901. 

Rumnio: Riforma Medica, 1900. 

Sainton et Ferraud: Bull, de la Soc. M6d. des Hftp. de Paris, 1901. 

Scheffmacher : Deutsche Archiv f. klin. Med., 1901. 

Siegert: Arch, de M^. des Enfants, 1900. Jahrbuch f. Kinderheilk., 1901. 

Thomas: Revue Hebdoni. et Laryng., d'Otol. et Rhinol., 1900. 

Torri: Suppl. al Policlinico, 1900. 

IJlrich: Nordiskt raediunskt Archiv, 1900. 

Verriest: Belgique MMicale, 1900. 

Ziegler: Lehrbuch der Allgemeinen und speriellen pathol. Anat., 1901. 



INDEX. 



Abnormalities of thyroid, 10 
Accessory thyroid, 13 
Achondroplasia, 180 
Acute thyroiditis, 129 

suppurative, 131 

gangrenous, 132 

rheumatisnial, 132 

mumps, 132 

grippe, 133 

malaria, 133 

typhoid, 133 

pyemia, 133 
Adiposis dolorosa, 248 
Anatomy, thyroid, 8 

parathyroid, 17 
Analysis, methods of, 57 
Anangioplasia, 173 
Anesthesia, 107 
Anthrax, 126 
Aorta, 44 
Arsenic, 68 
Ateleiosis, 175 

B 

Basedow's disease, 197 

blood pressure, 227 

insanity in, 218 

incomplete, 226 

pathology, 223 

symptoms, 203, 209 

scrum treatment, 230 

skin pigmentation, 219 

treatment, 228 

urine, 222, 226 
Blood changes after thyroidectomy, 

26, 40 
Bone marrow, extract of, 5 
Brain, desiccated, 6 
Bright's disease, 237 
Bromin in thyroid, OS 



C 

Cancer, 140 

Cachexia strumipriva, 118 

Castratos, 2 

Chemistry, 56 

Complications, surgical, 104, 106 

Congestion, 121 

pathologic anatomy, 122 
Cretinism, 144 

in animals, 161 

parathyroids in, 153 

pathology, 154 

symptoms, 155 
Cystic goitre, 90 
Cysts, surgery of, 113 

I) 

Dangers of operation, 100, 103, 107 
Desiccated brain, 6 
Development of thyroid, 39 
Dibromostearic acid, 68 
Diphtheria, 125 

toxin, injection of, 127 

E 

Eclampsia, 241 
Embryology, 8 
Emergency operation, 100 
Enucleation, 110 
Epilepsy, 237 
Extirpation of thyroid, 23 

of parathyroid, 29, 34, 37 
Extracts of bone marrow, 5 

kidney, 7 

liver, 6, 7 

lymphatic glands, 7 

ovaries, 3 

parotid gland, 5 

pituitary body, 5 

prostate gland, 7 

spleen, 5 

suprarenal, 7 



259 



260 



INDEX. 



Extracts of testicles, 2 
thymus, 4 



Feeding thyroid, 35 

influence after thyroidectomy, 
55 
Fetal thyroid, functions of, 252 
Functions of thyroid, 21, 69, 72 

parathyroid, 33, 72 

Notkin's theory, 60 

antitoxic theory, 70 

G 

Gangrene, 132 
Geromorphine cutan^e, 180 
Glycocholate of soda, 6 
Glycosuria, 235 
Goitre, endemic, 73 

anatomy, 81 

congenital, 70 

distribution of, 74 

etiology of, 76 

experimental production of, 77 

infection theory, 70 

follicular goitre, 86 

struma vasculosa, 87, 05 

struma fibrosa, 88, 05 

symptomatology, 80 

struma parenchymatosa, 04 

struma colloide, 05 

mixed goitre, 05 

thyroid feeding in, 08 

thymus feeding in, 08 

iodin in, 08 

sporadic, 80 
Grippe. 133 

H 
Heart, effect of thyroid feeding 

on, 40 
Hemorrhages, 105, 248 
Historical, 1 
Histology, thyroid, 14 

parathyroid, 17 
Hydatid cysts, 142 
Hypophyses cerebri, 53 



Infantilism, myxedematous, 1G4 

etiology, 165 

non-myxedematous, 174 

symptoms, 165 

type Loraine, 169 
Infectious diseases, 121 
Inoculation experiments, 126 
Iodin, 57, 50, 64 
Impotence, 245 

Insanity in Basedow's disease, 218 
Isthmus, removal of, HI 

K 

Kidney, 7 

L 
Lactation, 43 
Ligature of arteries, 112 
Liver, 7 
Lymphatics, 12 

M 
Malignant diseases of thyroid, 112 
Malaria, 133 
Measles, 125 

Menstrual disturbances, 238 
Metabolism experiments, 44 
Menstruation, 41 
Mental disease, 248 
Mucin, 8 
Mumps, 132 
Myxedema, 183 

incomplete, 180 

production of, 33 

symptom, 183 

treatment, 106 

urine, 180 

N 

Nerves, 28, 35 
Xervous diseases, 246 
Nitrogen metabolism, 46 

O 

Obesity, 234 

Organs of generation, 41 

Oxydase. 07 

Oxygen, metabolism of, 45 



INDEX. 



261 



Parathyroids, anatomy, 17 

histology, 17 

cretinism, 153 

infectious diseases, 124 
Paralysis agitans, 247 
Parotid gland, G 
Pituitary body, 5 
Pneumococeus, 126 
Precocious development, 179 
Pregnancy, 42 
Progeria, 179 
Prostate, 7 
Puberty, 42 
Pyemia, 133 

R 
Rheumatismal thyroiditis, 132 

S 
Sarcoma, 142 
Scarlet fever, 125 
Senilism, 178, 236 
Skin in Basedow's disease, 226 

diseases of, 247 
Smallpox, 125 
Splenic extract, 5 
Sj)ermin, 3 

Suppurative thyroiditis, 127-131 
Sulphur, 06 

Surgery, indications for operation, 
100 

emergency operation, 100 

tracheotomy, 101 

dangers of, 101-103, 107 

statistics of, 104, 114 

complications, 104, 106, 115, 
118 



Surgery, hemorrhage, 105 
anesthesia, 107 
preparation, 107 
technique, 108 
enucleation, 110 
isthmus, removal of. 111 
malignant disease, 112 
ligature of arteries, 112 
cysts, 113 
wounds, 119 

Syphilis, 139 

T 

Temperature alter thyroidectomy, 

54 
Tetanus toxin, 127 
Tetany, 115, 239 
Thymus gland, 4 
Thyroidismus, 48 
Thyroid feeding, 46, 48, 49 
Thyroglobulin, 58 
l\vroantitoxin, 56 
Tracheotomy, 101 
Tuberculosis, 134 
Typhoid bacillus, 126-133 
Type Loraine, 169 

U 
I'rine after thyroidectomy, 54 
in myxedema, 189 
Basedow's disease, 226 



r 



Veins, 12 



W 



Weight of thyroid, 11 
Wounds, surgery of, 119 



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MAY 1 
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