With Compliments of the Author. 
[Extracted from the Transactions of the Medical Society of the 
State of Pennsylvania. Yol. XII. 1879.] 
A CONTRIBUTION TO THE CLINICAL STUDY OF 
EXOPHTHALMIC GOITRE. 
By WILLIAM PEPPER, A.M., M.D., 
PROP. OF CLINICAL MEDICINE IN THE UNIVERSITY OF PENNSYLVANIA. 
Many names have been applied to the peculiar condition of dis- 
ease characterized by rapid action of the heart, protrusion of the 
eyeballs, and enlargement of the thyroid gland. Most of them are 
open to the objection of not indicating definite!}' either the princi- 
pal symptoms, or the essential character of the affection. It is on 
this account that I much prefer the name “Exophthalmic Goitre” 
to either that of Graves’ disease, or of Basedow’s disease, by one or 
the other of which it is most commonly described. 
Exophthalmic goitre is not a distinct and specific disease in the 
sense that typhoid fever and acute croupous pneumonia are, but 
still it has a perfectly well-established claim to its place in our 
nosology. It is true that in well-marked cases there are certain 
features which are dependent on the anaemia which is so frequently 
present, and others which are due to the general neurasthenia that 
is usually attendant. But apart from these, there is the clearly 
defined group of symptoms first mentioned, which are so peculiar 
and so constantly associated in this disease as to clearly establish 
its separate identity, and to show that it is connected with some 
special morbid condition. A good idea of the cause of exophthal- 
mic goitre in its aggravated form may be gathered from the follow- 
ing history. 
Case I.—R. T., a tall, spare woman of nervous temperament, 
when about 27 years of age, suffered a severe disappointment in a 
love affair. Soon afterwards she began to present symptoms of im- 
paired nutrition, loss of color, emaciation, debility, etc. She became 
much more highly nervous and excitable. At the same time the 
action of the heart became rapid and excited, and the thyroid gland 
enlarged. There was marked irregularity of menstruation. There 
was a marked anaemic bellows murmur over the base of the heart. 
The carotid arteries pulsated violently, and were the seat of a strong 2 
CLINICAL STUDY OF EXOP EITIIALMIC GOITRE. 
thrill and aneurismal bruit. There was also pulsation of the thy- 
roid gland, with thrill and murmur. Under the use of iron, digi- 
talis and tonics, she improved so much that she discontinued treat- 
ment. Before long she suffered from a return of all the above symp- 
toms in an aggravated form, and, in addition, there was prominence 
of the eyeballs ; but again she found relief, and during the next five 
years she had several similar relapses, though each time the symp- 
toms were more advanced. The degree of enlargement of the thy- 
roid varied considerably, being extremely marked at times. Both 
lobes were equally affected. 
The prominence of the eyeballs also varied much from time to 
time; during several of the attacks, being so extreme that the eye- 
lids would not close over them. On several occasions there was 
slight conjunctivitis, alwa}rs easily relieved. The attacks were 
always marked by a great increase in her debility and nervous ex- 
citability. The heart’s action never regained its normal state, but 
continued rapid and easily excited by slight causes. At times the 
pulse was exceedingly rapid, 130 to 150 in the minute. After seve- 
ral such attacks her general health became permanently impaired. 
The bellows murmur became harsher in character. The area of 
cardiac dulness increased, and the sounds of the heart became sharp 
and weak, indicating the development of dilatation with slight mitral 
insufficiency. (Edema of the feet and other evidences of impaired 
circulation now appeared. In the spring of 1864 she again came 
under my observation, and in far worse condition than at any pre- 
vious time. She had been suffering greatly for some time, and had 
for several years used stimulants freely. The heart’s action was 
very rapid and feeble, and there was violent pulsation in the cervical 
vessels. The thyroid gland had diminished somewhat in size, but 
was hard and inelastic. The eyeballs still protruded greatly ; there 
was no inflammation of the cornea or conjunctiva. There were 
oedema and ascites, and a few days later jaundice appeared and was 
soon followed by death. 
At the post-mortem examination, the heart was much enlarged, 
and its cavities, especially the right ventricle, extremely dilated ; 
both the mitral and the tricuspid leaflets presented thickening along 
their edges and were slightly insufficient. The thyroid gland was 
still enlarged; its tissue was dense and very hard from interstitial 
fibroid change. It was infiltrated with serum, but there was no 
cystic degeneration. The cervical ganglia of the sympathetic nerve 
were not examined. 
It may be observed, in the first place, that in the above case the 
subject was a woman, and experience shows that exophthalmic CLINICAL STUDY OP EXOPHTHALMIC GOITRE. 
3 
goitre occurs more frequently in the female sex. Of 38 fully devel- 
oped and undoubted cases of which I have preserved more or less 
full notes, 31 occurred in females, and 7 in males; and the same 
preponderance of females obtained in over 30 more or less typical 
cases which I have not used in the preparation of this sketch,1 The 
disease is more frequent in early adult life, but it has been met with 
at all ages. The earliest period at which I have met with a fully 
developed case was at ten years, and on the other hand I have seen 
several instances of it at the age of fifty-five, sixty, and even later. 
Before proceeding to consider more fully the causes, it is desira- 
ble to have a definite idea as to the pathological condition present 
in this atfection. It will be seen at once that the leading symptoms 
are dependent upon a disturbance of the action of the heart, and of 
the carotid arteries with their bi’anches. The disturbance of the 
heart itself is nearly always one of the most marked symptoms, but 
it must be clearly understood that the other symptoms cannot be 
directly traced to this disturbance of cardiac action. Exophthalmic 
goitre may exist in its most intense degree without any organic 
changes in the heart. It is indeed true, that when the disease has 
been long continued, evidences of serious impairment of the heart’s 
function often appear; but these are usually to be explained by 
degeneration of the walls of the heart, with dilatation of its cavities 
consequent upon prolonged anaemia and malnutrition. Again, while 
it is further true that exophthalmic goitre sometimes appears in 
patients who are subject to organic disease of the heart, there is 
always in such cases an additional element of morbid vascular action, 
while innumerable cases of organic heart disease of all types occur 
without the presence of the characteristic symptoms of exophthalmic 
goitre. Since, then, organic heart disease is either an accidental co- 
incidence or a late complication, it is evident that the intense func- 
tional disturbance of the heart, which is so constant and so early a 
symptom, must be due to some morbid condition of the ganglia and 
plexuses of nerves controlling its action. 
The only satisfactory explanation of the remarkable symptoms 
connected with the cervical vessels and thyroid gland and the eye- 
balls, is to be found likewise in a morbid state of the vaso-motor 
nerves controlling the carotid trunks and their branches. The thy- 
roid arteries are greatly dilated, and the enlargement of the gland 
which takes place is found to depend anatomically upon exti’eme 
1 These cases have occurred in private practice, or at the medical dispen- 
sary service of the University of Pennsylvania. The latter cases were re- 
corded by Dr. R. G. Curtin. 4 
dilatation of the vessels in its substance, together with infiltration 
with serum and some hyperplasia of the gland tissue. In like man- 
ner the protrusion of the eyeballs, about which so many theories 
have been advanced, is now recognized as being due to swelling of 
the post-ocular intraorbital fat, from hypenemia with oedema and 
sometimes with hyperplasia. 
CLINICAL STUDY OP EXOPHTHALMIC GOITRE, 
Accordingly the view which is now almost universally held, with 
regard to the explanation of the symptoms of exophthalmic goitre, 
is that there is a morbid condition of the cervical sympathetic gan- 
glia and the cardiac plexus of nerves. 
Attempts have been made to show that this morbid condition is 
really connected with grave anatomical lesions of the nervous gan- 
glia involved, and a few cases have been recorded by reliable ob- 
servers, where such lesions have been actually detected. It may, 
however, safely be affirmed, that while such grave lesions undoubt- 
edly occur, and may serve as a cause of this peculiar affection, it is 
by no means necessary that they should exist for it to be intensely 
developed. Examinations of undoubted cases by other competent 
observers have failed to reveal any lesions of these parts. I have 
myself had the opportunity of making a post-mortem examination of 
three cases. In one the cervical ganglia were examined carefully and 
found to be healthy. In one they appeared healthy on superficial 
examination, but were not examined microscopically. In one they 
presented slight increase of pigmentation of the nerve cells, and 
some apparent increase of interstitial fibrillar tissue. 
The frequency with which cases of the most aggravated type re- 
cover entirely is destructive to the view that actual organic lesions 
of the nervous ganglia are necessarily or even frequently present. 
Finally all analogies with other parts of the nervous would 
favor the view that a state of reduced and exhausted activity of these 
ganglia might fully account for the striking symptoms produced. 
I believe myself that in the great majority of cases the condition is 
of this latter kind ; and while in some instances exophthalmic goitre 
is due to organic disease of the nervous system, it is more frequently 
only a modality of neurasthenia, that is to say, a state of exhaus- 
tion of nervous power with irritability, specially localized upon the 
cardio-carotidean tract. AVe are familiar with other instances where 
such a morbid condition of nervous system affects special localities, 
but in none is the localization more definite or the symptoms more 
characteristic than in the affection we are considering. 
In returning to examine more at length the causes of exophthalmic 
goitre, we will be struck with the fact that they seem to be exclu- 
sively such as are apt to produce depression and exhaustion of the CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
5 
nervous system, if not actually organic disease. In most instances 
there will further be found a previous state of nervous suscepti- 
bility and weakness, constituting the familiar nervous temperament 
which must be regarded as a predisposing cause. Not rarely the 
exciting cause will be found to be some sudden and severe shock to 
the emotional nervous system. Thus 1 have known in several in- 
stances the initial symptoms to date from a sudden and severe fright; 
from disappointed affections ; from severe and wearing anxiety in 
connection with marriage; from protracted strain in supporting 
severe reverses of fortune, etc. etc. 
In other instances the causes are of a more directly exhausting 
character, as for example, rapid, repeated, and frequent pregnancies, 
exhausting lactation, profuse and repeated hemorrhages, etc.; of all 
of which I have seen several instances. In addition to these well 
recognized causes, I have met with several cases in which, conjoined 
with interference with nutrition and exhausting discharges, there 
was a marked element of prolonged reflex irritation, which incline 
me to believe that the peculiar morbid state of the nervous centres 
affected in this disease may be induced both directly through the 
influence of various depressing causes, and also indirectly through 
the exhausting effects of severe and long-continued reflex irritation. 
The two following cases may be cited in illustration of this point, 
as well as on account of the interesting symptoms and course which 
they pursue. 
Case 11. Chronic Intestinal Catarrh; Extreme Nervous Disturb- 
ances; Anaemia; Exophthalmic Goitre with rapid Action of Heart; 
Rapid Loss and Gain of Flesh; Recovery.—Miss A., ret. 20, although 
generally healthy, had always been nervous. She had always been 
used to eating unwholesome food, candy, cake, sugar, with quantities 
of tea and coffee, and insufficient food of plain nourishing character. 
In the summer of 1876 she attended camp meeting, was subjected to 
great nervous excitement, and was much exposed at same time. 
Severe diarrhoea resulted and was .not checked. No attention was 
paid to diet or to avoidance of exposure. The stools were frequent; 
twelve to twenty on some days, thin, whitish, and fetid. This con- 
dition became chronic. Soon afterwards, in September, 1876, she 
noticed palpitation of the heart, with dyspnoea, and enlargement of 
the thyroid gland. She grew weak, and lost flesh rapidly. She be- 
came extremely nervous, and very lachrymose, so that she wept on the 
slightest cause. Her temper was not particularly changed, except 
that she became more petulant. Frequently, an ordinary remark 
quietly addressed to her would cause a burst of tears. By Christ- 
mas, 1876, exophthalmos began, and rapidly increased until her eyes 6 
CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
were very prominent. She continued in about this same condition, 
despite medical treatment, until October 20, 1877, when I first saw 
her. The diarrhoea had persisted with the same character of stools. 
Menstruation had ceased five months previously. She had lost 
much flesh, her weight being scarcely ninety pounds, whereas four- 
teen months previously it had been one hundred and forty pounds. 
Her appearance was shocking on account of the extreme exophthal- 
mos and the very large goitre. She was unable to close the eyelids. 
The action of the heart was constantly rapid, and frequently it rose 
as high as 175 to 185. There was a soft anaemic cardiac murmur 
over the base. The thyroid gland pulsated very strongly, and was 
the seat of a strong diffused thrill, and of a loud, shrill murmur. 
When the stethoscope was applied over the temporal fossa, to the 
anterior part of the parietal bone on either side, a distinct high- 
pitched murmur was audible. 
She was immediately placed on the use of skimmed milk (of which 
she soon drank two quarts daily) with stale bread, and two soft- 
boiled eggs daily. Nitrate of silver with opium in pill form were 
given, and fifteen drops of tincture of digitalis thrice daily. The 
diarrhoea was soon controlled, after which dialyzed iron was sub- 
stituted for the silver and opium, and bromide of potassium gr. viij 
was given in combination with the digitalis. All of her symptoms 
improved rapidly, and she gained flesh quickly. She soon wearied 
of the restricted diet, and about the middle of December she stopped 
all treatment, and returned to the use of a mixed diet. Diarrhoea 
soon returned and she rapidly lost the flesh she had gained; and 
all of her symptoms, the cardiac excitement, goitre, and proptosis 
again increased. On February 7,1878, I saw her again and directed 
a return to a similar diet, and to the use of silver and opium 
for a time, to be followed later by digitalis and dialyzed iron. 
The diarrhoea was again cheeked readily, and rapid improvement 
commenced immediately and continued without any interruption. 
The dialyzed iron was increased gradually from ten to forty drops, 
and its effects were definite and gratifying. If suspended for even 
two or three days she asserted that she missed its tonic influence. 
Her gain in weight was as follows: from Feb. 7 to March 19 vforty 
days), from one hundred to one hundred and twenty-five lbs.; from 
March 19 to June 20 (ninety-three days) from one hundred and 
twenty-five to one hundred and forty-two (seventeen lbs.). She 
seemed to make blood and flesh so rapidly that, at that time, the 
dose of dialyzed iron was lessened to ten drops. She increased to 
one hundred and fifty pounds in the course of six weeks, having- 
gained sixty pounds in all within a period of nine months. There CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
7 
was a correspondingly rapid improvement in the nervous symptoms. 
She ceased to be lachrymose, and lost to a great extent the mor- 
bidly excitable, impressionable character she had before presented. 
Her color became healthy. The prominence of the eyes disappeared 
almost entirely by June 20, 1878, and when I last saw her, Dec, 14, 
1878, it had not returned. The enlargement of the thyroid gland 
had also gone. By June, no hsemic murmur could any longer be 
heard over heart, neck, or temple ; and all pulsation, thrill, and mur- 
mur had gone from the region of the tigroid gland. Menstruation 
returned in May, 1878, after an absence of fifteen months, and sub- 
sequently continued regularly. The pulse still continued somewhat 
too rapid, and was readily accelerated by effort or excitement. Up 
to December, 1878, she still continued a diet chiefly of milk and 
farinacea, with but little meat, and no tea or coffee. 
Case 111. Chronic Intestinal Catarrh ; Anaemia; Exophthalmic 
Goitre; Rapid Action of Heart; Repeated Epistaxis ; Rapid and 
Extreme Emaciation; Recovery.—Mrs. was sent to me in 
August, 1878, by Dr. Birnie, of Maryland. She was about 22 or 23 
3rears old, and had recently been married. From 1870 to 1873 she 
resided in an unhealthy locality, and there began to have occasional 
spells of feverishness which soon became accompanied by diarrhoea. 
These attacks would usually last three or four days at a time. There 
does not seem to have been any fully developed malaria. After return- 
ing to her home, which was in a healthy mountainous district, she 
continued to have occasional spells of diarrhoea with feverishness. 
She did not, however, lose much flesh or strength. In spring of 1876, 
enlargement of the thyroid gland and prominence of the eyeballs 
was first noticed. At that time she weighed one hundred and four 
pounds. In June, 1877, a severe attack of diarrhoea began and con- 
tinued until the following October. During this time she rapidly 
lost weight until she reached sixty-eight pounds. The enlargement 
of the thyroid gland and the exophthalmos also increased rapidly 
and attained proportions as great as at any subsequent period. 
After the cessation of the diarrhoea in October, 1877, she began to 
gain weight, and during the ensuing winter reached one hundred 
and eight pounds. There was, however, no improvement in the 
condition of the eyeballs or of the thyroid gland. She continued 
weak also, and with marked excitement of heart’s action. 
Diarrhoea returned in June, 1878, hut for some time previously 
she had been losing in strength and probably in flesh. By the time 
I first saw her in August she weighed less than seventy pounds. 
The character of the discharges in all the attacks of diarrhoea was 
similar; thin and watery, with particles of undigested food, hut 8 
CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
without either blood or pseudo-membrane. There has been very 
frequent complaint of pain at the lower part of the abdomen. In 
addition to the above symptoms, there have been for several years 
quite frequent and copious hemorrhages from the nose. Menstrua- 
tion has always been scanty and irregular, and lately has been ab- 
sent entirely for a number of months; it occurred twice in 18*17, 
and three times in 1878. During the summer of 1878, oedema of the 
ankles frequently appeared towards evening. 
On examination in August, 1878, her condition appeared very 
alarming. She was extremely emaciated and feeble. The immense 
protrusion of the eyeballs, and the enormous enlargement of the 
thyroid gland gave her a shocking appearance. She was unable to 
cover the cornese, but no inflammation had occurred. Emaciation 
wras extreme; her weight did not reach seventy pounds, and the 
skin and mucous membranes were bloodless and slightly sallow. 
The tongue was tremulous, red, and smooth. Appetite was capri- 
cious and somewhat abnormal. The bowels were moved frequently, 
from four to eight times in twenty-four hours, the character as above 
given. Respirations were frequent and increased markedly by the 
slightest exertion. The pulse was very small, weak, and frequent; 
in the sitting posture, it averaged 140. Exertion brought on severe 
palpitation. The heart sounds were sharp and feeble, with strong 
hseniic murmurs at the base, and along the pulmonary artery. The 
carotids throbbed excessively, and the thyroid was the seat of strong 
diffused pulsation and thrill, with loud humming murmur on auscul- 
tation. No venous hum could be heard on ausculting the temples. 
There had been frequent epistaxis of late. The feet and ankles were 
oedematous. The urine was pale, of low sp. gr. 1009-1010, but con- 
tained no albumen. 
She had already used iron, tonics, bismuth, and ergot. I now 
directed her to use an exclusive diet of milk and arrowroot, to 
have absolute rest, and to take a pill of nitrate of silver, gr. i, 
with powdered opium gr. t thrice daily. She went directly to the 
sea-shore, but the climate did not suit her; and although she had 
gained somewhat when I next saw her in September, the diarrhoea 
and attacks of epistaxis continued. She was then directed to 
remain in bed for several weeks, the diet was restricted to light 
broths, milk and water, and arrowroot, and pills of sugar of lead 
and opium were given. The diarrhoea was soon checked; she was 
thoroughly anointed daily with oil, and her diet was cautiously 
enlarged. In consequence of febrile symptoms with a tendency to 
night sweats, she took for a time six grains of quinia sulphate daily 
in divided doses. On September 25th, there was such marked im- CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
9 
provement that she returned home to Baltimore, and resumed the 
use of nitrate of silver and opium, as the stools, although solid, were 
too frequent. Dialyzed iron was also given, at first in doses of 
eight drops.three times a day. The nitrate of silver was continued 
for more than two months, with occasional short interruptions. The 
iron was increased to thirty drops three times a day, and was con- 
tinued until May 1, 1879. The diet was rigidly restricted for several 
months, and then cautiously enlarged. 
Improvement was steady and rapid. Menstruation became regu- 
lar in March, 1879. By February her weight had gone up to one 
hundred and two. The prominence of the eyeballs had almost dis- 
appeared, and there was marked decrease in the enlargement of the 
thyroid. The heart’s action was still too rapid and readily accele- 
rated. Epistaxis became very rare. Since then, until the present 
time, May, 1879, the improvement has continued. There is still a 
tendency to rather frequent movement of the bowels from trifling 
causes, and for this she has again resumed nitrate of silver and a 
more restricted diet. There has been still further reduction in the 
size of the tigroid. She is now bright and active, and would not be 
recognized by any one who had first seen her in August, 1878. 
It will be seen from the above cases, and from what has been 
said, that anaemia is a very frequent attendant on this disease. The 
fact has long been recognized that, in all conditions of neurasthenia, 
anaemia, both general and of the nervous centres, is a most impor- 
tant factor. This certainty holds true in regard to exophthalmic 
goitre. In many cases a well-marked state of anaemia is produced 
before the characteristic symptoms appear, and it may be safely re- 
garded as a powerful predisposing cause. When the anaemia has 
become marked, and a state of general susceptibility and weakness 
has been developed, it needs only some special circumstance or some 
special pre-existing vulnerability to localize the morbid action upon 
the ganglia and nerves involved in exophthalmic goitre, in order 
that the symptoms of this affection may be induced. In some cases, 
pronounced anaemia does not precede, but follows the characteristic 
symptoms, but it is then also due to the continued operation of the 
depressing causes. It may be concluded that anaemia is one of the 
most constant conditions in exophthalmic goitre, though among my 
notes of thirty-eight cases, I find twelve in which no positive anae- 
mia existed. There does not seem to be any organic lesion of the 
blood-making tissues, such as tiie spleen, lymphatic glands, or mar- 
row of bones. In those cases where I have examined the blood, 
there has been no increase in the number of white corpuscles, but 
merely a marked decrease in the red globules; though I believe the 10 
CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
accurate enumeration of the blood corpuscles in this disease is still 
a desideratum. 
The three chief symptoms, as already mentioned, will repay more 
minute study. It is true that, in some cases, one or the other of them, 
as either the disturbance of the heart’s action, the enlargement of the 
thyroid gland, or the protrusion of the eyeballs may be wanting; but 
it is certainly rare in well-developed cases, for any one of them to be 
entirely absent, although they present frequent variations in degree of 
intensity. The disturbance of the heart’s action is the most constant, 
and is usually the first to appear. The pulse becomes unaccounta- 
bly rapid. Sometimes the patient is scarcely conscious of this, while 
with others there is a sense of praecordial distress, with at times 
severe spells of palpitation and tumultuous action. I have occa- 
sionally known the pulse to have continued rapid, presenting unusual 
resistance to the controlling influence of digitalis and other remedies, 
for a long period before the other symptoms ensued. The pulse rate 
usually rises to 120 and over, and in severe cases I have known it 
150, 160, and even 180, and this for considerable periods of time 
together. The heart’s sounds are usually sharp and clear, and later 
are apt to become feeble, even if valvular disease is absent; and a 
murmur or murmurs will usually be heard at some period of the 
case. These are generally soft and blowing in character, systolic in 
time, and located over the base of the heart, extending along the 
great vessels. In some cases they may be due to irregular muscular 
action, but are for the most part amende in character. 
It is perhaps due to the impaired nutrition usually attending, that 
such intense and prolonged excitement of the heart’s action does 
not more frequently become associated with hypertrophy. But the 
symptoms may persist for a considerable time without such a result; 
and usually it is only when advanced malnutrition and amemia have 
gravely impaired the tenacity of the heart’s muscle that passive 
dilatation occurs. In connection with the anaemic murmurs referred 
to over the heart, I would call attention to the unusual points at 
which such murmurs may be heard in these cases. Russell speaks 
of strong bruits over the cervical vertebrae. I have heard them 
there myself, and in Case 11. have described the loud murmurs which 
were audible over the temporal fossae, as well as over the vertex. 
The murmur which is frequently heard over the thyroid gland is 
diffused and prolonged, but may be quite high pitched and shrill. I 
may here allude to the violent throbbing often observed in the arte- 
ries and veins. This is especially marked in the tortuous and en- 
larged thyroid vessels and in the carotids and jugulars, but it is not 
rarely met with, also, in the abdominal aorta, where it may be intense CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
11 
and cause serious distress. A distinct thrill ma}r often be felt over 
the throbbing vessels, and much more rarely over the heart itself. 
Its presence is very easily accounted for, by the violent excitement 
of vascular action and by the altered condition of the blood. As 
would be expected it is most constant and intense over the thyroid 
gland. These same conditions quite often lead to strong and annoy- 
ing subjective sensations of sound in the head, resembling the beat- 
ing of hammers, the dashing of water, the ringing of bells, or loud 
whizzing or purring. 
The enlargement of the thyroid, the second of the characteristic 
symptoms of this disease, is also veiy constant. It appears early 
and usually attains considerable magnitude in marked cases. I have 
more frequently observed both the lobes to be equally enlarged, 
though in some cases the enlargement is not symmetrical. It will 
be noted that the enlargement of the thyroid gland varies remarkably 
from time to time. In females it is not unusual for it to increase at 
or before the menstrual period. At such times I have known sudden 
and abrupt increase in the enlargement to occur in a single hour, 
even causing great distress to the patient. As a rule, a sense of ful- 
ness and weight is all that is complained of, but at times there may 
be an occasional feeling of oppression with some difficulty in degluti- 
tion. In but one case have I known pain in the thyroid to be com- 
plained of. The enlarged gland pulsates distinctly, and when grasped 
by the hand, we find that this is attended with distinct distension 
of its substance. In addition to the pulsation, there are also a 
marked thrill and a distinct murmur. The thyroid enlargement 
varies with the intensity of the general symptoms. At different 
periods of the same case, it may vary from a slight degree to a 
swelling so enormous as to cause great deformity. As the symp- 
toms subside and the case approaches a favorable conclusion, it 
diminishes and even disappears entirely. The gland is at first pain- 
less, elastic, and soft, though at times it may be extremely tense. 
In long-continued cases of unfavorable character, it may diminish 
in size, but become hard, dense, and resisting from a fibroid change. 
It is not unusual for a certain amount of serous infiltration of its 
tissue to occur; but any cystic degeneration, such as is met with in 
some other conditions of this gland, is of rare occurrence in this 
disease. There is no relation between this thyroid enlargement and 
true goitre. Where the latter disease is endemic and frequent, ex- 
ophthalmic goitre is no more liable to occur than elsewhere. It is 
important to note this distinction, as I have met with not a few cases 
of true goitre, associated with some disturbance of the heart, which 
has caused some difficulty in diagnosis. 12 
CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
The protrusion of the eyeballs is one of the most important symp- 
toms, especially in a diagnostic point of view. The increased action 
of the heart and the thyroid enlargement usually become marked be- 
fore the exophthalmos reaches a high degree, but von Graefe pointed 
out the fact that if a patient, even in the early stages, be requested to 
look downward, the upper eyelid will be seen not to follow perfectly 
the ball, so that a segment of the cornea and a part of the sclera will 
remain visible. This test may be safely applied in suspected or doubt- 
ful cases in the early stages. 1 have already mentioned the anatomical 
changes (hyperaemia, oedema, and sometimes hyperplasia of the intra- 
orbital fat) which produce the protrusion of the eyeballs. In severe 
cases this protrusion becomes so marked that the patient is unable 
to close the lids. Inflammation of the conjunctiva is by no means 
common, considering the long continuance of such exposure of the 
globe of the eye. I have seen several mild attacks of this trouble, 
and there are cases on record in which serious inflammation with 
ulceration of the cornea has occurred. The vision is not impaired. 
It will be very frequently (14 in 27 cases) observed that the pupils 
are dilated, though they still respond to light. When the protrusion 
of the eyeballs reaches an intense degree, so that the sclerotic, with 
its enlarged vessels, is widely exposed; and when the enormous en- 
largement of the thyroid, with the fulness and violent pulsation of 
the cervical vessels causes extreme disfigurement of the neck; while 
the anaemic and emaciated appearance of the patient brings into 
bolder relief these conditions, the physiognomy of this disease is 
one of the most striking and hideous that can be conceived. 
There are a few other symptoms which require mention. Menstrual 
disorders are among the most frequent of these. It would also appear 
that they occasionally act as the cause of exophthalmic goitre, since 
it seems probable that the prolonged reflex irritation from a diseased 
uterus, acting upon a system predisposed, may serve as the exciting 
cause. More frequently by far, however, the uterine disturbances 
appear as symptoms and are dependent upon the anaemia and neuras- 
thenia. In more than one-half of my cases, irregularity or absence 
of menstruation occurred, and this was especially7 marked in the cases 
I have here cited. In one instance the menses were absent for three 
months before the attack, but more frequently, as in Cases 11. and 
111., amenorrhoea does not appear until marked anaemia has been 
developed. As long as menstruation continues, the enlargement of 
the thyroid and the exophthalmos may sometimes be noted to 
increase as each period approaches, and to again subside after the 
menstrual flow begins. So, too, when amenorrhoea has existed for CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
13 
some time, I have noted a marked reduction in the size of the thyroid 
to attend the reappearance of the menses. 
The nervous symptoms play an important part in the course of 
this disease. Those which are most marked are the extreme mobility 
and susceptibility of the nervous system. The patients become ex- 
tremely irritable and frequently capricious or perverse: sometimes, as 
in Case 11., they are excessively and ludicrously lachrymose, or they 
present fits of hysterical excitement, alternating with brooding 
depression of spirits. These conditions are always aggravated by 
fatigue or excitement. Vertigo and pains in the head are both 
occasionally complained of; the former was a marked symptom in 
no less than 19 out of 88 cases. Allusion has already been made 
to the subjective sounds, which are similar to those experienced by 
other anaemic patients, and are frequently observed in this disease. 
In some cases, excessive sensations of heat of the surface of the body 
are complained of, so that the patient can with difficulty bear even 
light clothing by day or hy night. Another symptom, which may 
be referred to the influence of the vaso-motor nervous system, is the 
occurrence of profuse and sometimes irregularly distributed sweat- 
ing of the surface, with or without flushing. The disturbance of the 
heart’s action has been carefully described, but in a considerable 
proportion of my cases dyspnoea was also present in a marked 
degree. It is usually of a paroxysmal character and attends the 
spells of palpitation of the heart. More or less shortness of breath 
may, however, be constantly caused by exertion. It is probable that 
the dyspnoea is in part due to pressure of the enlarged thyroid 
upon the larynx and trachea. 
Disorders of digestion are very frequent and of the utmost im- 
portance in this disease. Dysphagia occasionally occurs; of 38 
cases, 8 complained of it in a marked degree, and 2 others in a less 
degree. I would, however, call especial attention to the fact that in 
some instances the starting point of the disease appears to be some 
severe irritation of the gastro-intestinal mucous membrane. I have 
seen exophthalmic goitre rapidly follow a severe spell of gastro- 
hepatic catarrh with much vomiting; and I have cited Cases 11. and 
111. especially on account of the evident connection between the 
chronic intestinal catarrh and the subsequent development of ex. 
ophthalmic goitre. The interference with nutrition, so caused, un- 
doubtedly predisposes to this affection, and the reflex irritation from 
the inflamed mucous membrane probably aids in exciting it. 
It seems to me that uterine disease of certain sorts probably 
occupies a similar relation in some cases. 
Besides occasionally serving as a predisposing cause, gastro-intes- 14 
CLINICAL STUDY OP EXOPHTHALMIC GOITRE. 
tinal irritation is a very frequent complication, and aggravates the 
affection considerably. In much more than one-half of ray cases, 
dyspeptic disturbances of greater or less severity existed. The ap- 
petite is capricious, at times poor, at others craving and unhealthy. 
The stools frequently indicate a deficiency of bile, and there are often 
other evidences that—as might be expected from the state of the 
central circulation—the liver is congested: this is especially apt to 
be severe when dilatation of the heart has been developed. In cases 
accompanied with extreme anaemia, there is of course danger of fatty 
degeneration. In the first case I have here cited, the extreme degree 
of this change presented by the liver was probably chiefly due to the 
anaemia, and only in part, if at all, to the use of stimulants. It is not 
rare for jaundice to make its appearance towards the close of fatal 
cases. 
Among the most interesting and remarkable symptoms connected 
with the processes of nutrition and assimilation, is the rapid varia- 
tion in weight presented by some patients with this affection, when 
accompanied with chronic gastro-intestinal catarrh. Russell {Med. 
Times and Gaz., Sept. 2, 1876, p. 251) alludes briefly to this peculi- 
arity; but it is better illustrated by my Cases 11. and 111., to which 
the reader is referred. 
The hemorrhages and dropsies, which are of frequent occurrence, 
are usually due to a watery state of the blood. Epistaxis is the 
most frequent form of hemorrhage; in Case 111. it was of such rapid 
recurrence and large extent as to constitute a source of danger. 
(Edema of the feet is the usual form in which dropsy appears, here 
as in other anaemic states. It is only when the power of the heart 
has failed from fatty degeneration or dilatation, and when the 
alterations of the blood have become veiy marked, that general 
anasarca or internal serous effusions are observed. The urine very 
rarely contains albumen. 
It is not necessary to dwell upon the diagnosis of this disease. It 
is only in the earty stage, when von Graefe’s mode of detecting 
slight protrusion of the eyeballs will be of signal service; or in 
cases of true goitre in anaemic subjects with rapid action of the 
heart, that any difficulty can be experienced. 
The prognosis is, as a rule, favorable, unless dilatation of the heart 
with or without degeneration of its muscle, has supervened. In the 
latter case, the existence of marked dyspnoea, of pulmonary conges- 
tion, of general venous stasis, or of extensive dropsical effusions 
would be apt to usher in the fatal stage. Repeated hemorrhages, 
extreme anaemia, rapid loss of flesh, intractable diarrhoea, or jaundice, 
are also grave symptoms as indicating extreme depravation of blood CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
15 
and interference with important functions, hut still they are by no 
means necessarily of fatal omen, and the cases here given may serve 
as illustrations of the extent to which thej' may be present and yet 
a favorable result be secured. 
In 38 cases the result was unknown in 2; 4 died, of whom one was 
never under treatment, and had organic heart disease; 12 were cured, 
and 20 were relieved, and improved very markedly by treatment. 
The prognosis must, however, be very guarded as to the probable 
duration of the symptoms. Under any curative treatment, the 
affection is apt to be prolonged for many months; and it is only 
when we can succeed in detecting and removing all predisposing 
or exciting causes that may aid in maintaining it, and in placing 
the patient under the most favorable hygienic conditions, that a more 
rapid cure can be effected. Even after the subsidence of the exoph- 
thalmos and of the thyroid swelling, and when the general symptoms 
are greatly improved, the rapid action of the heart, with tendency 
to attacks of palpitation on small provocation, is apt to continue 
for an indefinite time. 
Treatment.—The results of treatment in exophthalmic goitre are 
usually spoken of as uncertain and unsatisfactory, and some authors, 
as Niemeyer, express doubts as to whether its course is modified by 
remedies. lam satisfied that this is the consequence of the adoption 
of special modes of treatment, based upon some partial theory of the 
disease, and employed with but little reference to the peculiarities of 
the individual case. 
There are, indeed, certain remedies which would appear to be 
almost always indicated, because the conditions they are designed 
to remove are constantly present. Among these is digitalis, which 
is the most appropriate and useful remedy for the disturbance of 
cardiac action observed in this affection. This drug may, there- 
fore, be used with advantage in most cases; but there are a few 
points of caution that may merit mention. Occasionally digitalis 
disagrees positively with the stomach, whether given in pill, 
tincture, or infusion; and, by the increased gastric irritation pro- 
duced, really aids in maintaining sympathetic palpitation of the 
heart. This remark applies to the treatment of exophthalmic goitre 
as well as of all forms of palpitation. Digitalin will occasionally do 
better than digitalis in such cases; but bromide of potassium with 
belladonna, or with small doses of aconite, will perhaps act more 
favorably. 
Ergot has been recommended in the treatment of exophthalmic 
goitre on account of its power of causing contraction of involuntary 
muscular fibre, and thus of favoring reduction of the calibre of the 16 
CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
dilated vessels. In a number of cases in which it was given, I have 
certainly seen a favorable change occur in the symptoms; though, 
as the ergot was not the only remedial agent employed, I cannot say 
how much of such result was due to its action. It is open to the 
objection of being apt to lessen appetite and disorder the stomach 
if long continued. 
Iron is in almost every case withoutexception to be administered 
in this affection. It is called for not only by the anaemia, so fre- 
quently present, but by the extreme mobility and weakness of the 
nervous system. In some cases the results of its administration in 
large doses are very brilliant. There can be no reasonable doubt as 
to its remarkable action in Cases 11. and 111. The form in which it 
is given, and the dose, must be carefully determined in each case. 
In general, it may be said that very large doses of whatever prepa- 
ration is selected must be given. So much discussion has occurred 
as to the value of dialyzed iron, and my own experience with it in 
suitable cases has been so gratifying, that I take pleasure in point- 
ing to the marked effects which, in Cases 11. and 111., are certainly 
in large part to be attributed to its action. 
But underlying this medicinal treatment, and of even greater im- 
portance, is a most careful study of the causes, of the condition of 
the general nervous system, of the principal functions and secretions, 
and especially of the diet and digestion. A rigid attention to hygiene 
must be insisted on. If there is any source of exhaustion or irrita- 
tion—and sometimes such causes are only to be detected by close 
questioning and examination—it must be removed. 
If digestive derangements exist, all other treatment must be 
suspended until they are rectified. A carefully restricted diet—if 
necessary, limited to milk, buttermilk, soups, broths, and light fari- 
nacea—must be insisted on in such cases, especially if chronic intes- 
tinal catarrh with diarrhoea exists. If evidences exist of congestion 
of the liver, an occasional gentle mercurial, followed by a mild saline 
laxative, may be called for. 
If, conjoined with weakness of digestion, there exists general nerv- 
ous debility, and marked over-action of the heart, I should strongly 
advise almost complete rest in bed, associated with gentle massage, 
and mild and pleasant diversion of the mind. The neurasthenia, the 
anaemia, the increasing failure in heart power, call for prompt and 
thoroughgoing treatment ; and., without the advantage of such a 
restorative basis of treatment as the above, remedies will produce 
but little good, in cases of less severity, attended with marked 
nervous s3anptoms,but with less debility, gentle travelling or change 
of scene will prove valuable. CLINICAL STUDY OF EXOPHTHALMIC GOITRE. 
17 
Careful attention should be paid to the complete cure of any local 
irritation co-existing. Such irritation is chiefly liable to be found 
in connection with the gastro-intestinal or the uterine mucous mem- 
brane. In the latter case, suitable local or general treatment should 
be instituted. In the former, when a chronic catarrhal state of 
mucous membrane exists, I would recommend in combination with 
careful diet, the use of nitrate of silver. I believe that this remedy, 
while exerting the very best local action, is at the same time a 
nervous tonic and antispasmodic of great value. 
Vegetable tonics, especially quinia and strychnia, will be found 
of much benefit in many cases, from time to time. 
Galvanization of the cervical sympathetic has been recommended, 
apparently on theoretical grounds, and I am not aware of any relia- 
ble clinical evidence in its favor; though I should, a priori, expect 
it to be of service. 
The enlargement of the tigroid gland requires no special attention 
or treatment. It fluctuates with the changes in the severity of the 
other symptoms ; and subsides, finally, as they are permanently re- 
lieved. Those modes of treatment, especially the use of interstitial 
injections of iodine or of other substances, which are of so much 
value in true bronchocele, are not to be recommended in this disease. 
When the protrusion of the eyeballs is extreme, a light bandage 
may have to be worn to prevent irritation of the conjunctiva. Von 
Graefe even recommended that, in extreme and threatening cases, the 
opening of the eyelids might be diminished by a surgical operation.