MYXEDEMA AND ITS DIFFERENTIAL DIAG- 
NOSIS FROM CHRONIC NEPHRITIS. 
BY 
M. ALLEN STARR, M.D., Ph.D., 
PROFESSOR OF DISEASES OF THE MIND AND NERVOUS SYSTEM, COLLEGE OF PHYSI- 
CIANS AND SURGEONS, NEW YORK ; CONSULTING NEUROLOGIST TO THE 
PRESBYTERIAN AND ORTHOPEDIC HOSPITALS. 
FROM 
THE MEDICAL NEWS, 
December 15 and 22, 1894. [Reprinted from The Medical News, Dec. 15 and 22, 1894.] 
MYXEDEMA AND ITS DIFFERENTIAL DIAG- 
NOSIS FROM CHRONIC NEPHRITIS. 
By M. ALLEN STARR, M.D., Ph.D., 
PROFESSOR OF DISEASES OF THE MIND AND NERVOUS SYSTEM, COLLEGE 
OF PHYSICIANS AND SURGEONS, NEW YORK J CONSULTING NEU- 
ROLOGIST TO THE PRESBYTERIAN AND ORTHOPEDIC 
HOSPITALS. 
There are very few diseases that have excited 
more interest in the medical world within the past 
decade than myxedema, and there are very few dis- 
coveries in the domain of therapeutics that have been 
so brilliant as the treatment of this disease by 
thyroid extract. The history of the discovery of 
the remedy reads like a novel. Tne clinical features 
of the disease were carefully determined by a com- 
mittee of the Clinical Society of London in 1889, 
but its origin remained unknown. The observations 
of surgeons, that a similar affection followed the 
removal of goiter, gave the first clue to the origin 
of the clinical symptoms. The brilliant researches 
of Horsley, by means of physiologic experiment, 
determined the function of the thyroid gland in 
maintaining the body-temperature and the nutrition 
of various parts of the system, and proved that the 
absence of the gland caused the symptoms of 
myxedema. Finally, the idea developed of trans- 
ferring to the human body the thyroid glands of 
animals, either by direct transplantation (Horsley 2 
and Kocher) or by subcutaneous injection (Murray) 
or by ordinary administration by the mouth (Mac- 
kenzie), for the purpose of removing the symptoms 
of myxedema, which were due to the absence of 
this substance from the blood. The success of this 
method completed the history of the affection. 
Those who have seen the very distressing physical 
and mental symptoms occurring in myxedema 
rapidly and progressively disappear under the ad- 
ministration of thyroid extract, until the patients 
are restored to perfect health, cannot but be im- 
pressed by the wonderful effect that the presence of 
this active principle in the blood has had. It has 
been my fortune to watch this transformation from 
a state of disease to a state of health in fourteen 
adults. The histories of several of these cases have 
been already published by myself1 and by others.2 
My object in reporting another case at this time 
is to call attention to certain features of myxedema 
that closely resemble the symptoms of chronic ne- 
phritis and to emphasize the importance of the dis- 
tinction between these two diseases. This can 
hardly be exaggerated, for many of the cases of 
myxedema that are now cured had been considered 
cases of nephritis of an incurable nature, a mis- 
take easily accounted for when we consider that 
the presence of albumin and of casts in the urine, 
together with an appearance of general edematous 
1 Transactions of the Association of American Physicians, 
1893, vol. viii, p. 361, three cases. 
2 Dr. George W. Crary, American Journal ot the Medical 
Sciences, April, 1894, two cases ; also, Dr. S. J. Meltzer, N. Y. 
Medicin. Monatschr., April, 1894, one case. 3 
swelling of the body, is uniformly noticed in this 
disease. After recording the history of the follow- 
ing case an attempt will be made to indicate the 
chief points of differential diagnosis. 
G. W. H., aged forty-five, had been perfectly 
well until the early part of 1892, when without any 
known cause he began to suffer from a gradually 
increasing swelling of the hands, face, nose, mouth, 
and tongue, which was accompanied by the appear- 
ance of a yellow pigmentation upon the hands and 
face and a decided thinning of the hair. This con- 
dition gradually increased during the summer, and 
he found that he was unable to perspire, no matter 
how hot the weather. During the autumn, in addi- 
tion to the symptoms mentioned, he noticed that 
his teeth were loose, that the gums were sore, bled 
quite frequently, and seemed to be soft; that the 
swelling of the mouth and tongue had become so 
great as to materially change the character of his 
voice, making talking monotonous and decidedly 
slower; and that the swelling also interfered with 
breathing easily through the nose, so that he kept 
his mouth open, and at times had some difficulty in 
swallowing. As winter came on he suffered more 
from the cold than he had ever done previously. 
The swelling had by this time gradually extended 
over the entire body, giving him the appearance of 
being rather fleshy, so that his tailor had to let out 
his clothing an inch-and-a-half about the waist. 
The appearance of his face during this time had 
progressively altered, and presented certain pecu- 
liarities ; the hair of the head had become coarse 
and rather thin; the hair of his moustache was also 
coarser than formerly and had become bristly, so 
that it could not be kept smooth as formerly ; the 
skin of the entire face was thickened and pig- 4 
mented ; this was particularly noticeable about the 
forehead, where deep wrinkles appeared, and around 
the eyes (which could hardly be opened to their full 
extent), and about the mouth, where the lips were 
thick and heavy; there wras a peculiar elevation oi 
the external corner of the eyebrows in the effort to 
Fig.i. 
open the eyes; and a thickening of the face at the 
side of the nose was very perceptible. His extrem- 
ities were also swollen and pigmented ; the skin all 
over the body was dry and scaly. His friends had 
noticed the slowness of his speech and the peculiar 5 
thickness of utterance. Many of these characters 
are well shown in his photograph (Fig. i), which 
was taken in May, 1894. 
The diagnosis of myxedema was made by his 
physician in San Francisco, in September, 1893, 
and the thyroid treatment had been begun about 
that time and kept up until May, 1894, when I first 
saw him. Whether the preparation used had been 
defective or imperfectly prepared I do not know; 
but his improvement had been slow, though per- 
ceptible, during the winter. When I saw him in 
May I observed, in addition to the symptoms and 
appearance already noticed, very marked supra- 
clavicular swellings, slightly subnormal temperature, 
a marked slowness mentally, attended by a tendency 
at times to feelings of depression and the charac- 
teristic speech of myxedema. He had not had 
hallucinations, and the mental hebetude was less 
than I have seen in other cases. Examination of 
the urine showed the presence of small amounts of 
albumin and a few large and small hyaline casts ; his 
pulse was slow—60—and rather hard and irregular. 
He felt himself unfitted to do business by rea- 
son of his condition, and though not suffering 
any pain, was decidedly uncomfortable and dis- 
tressed at his state. He was placed immediately 
upon the 5-grain tabloids of thyroid extract pre- 
pared by Burroughs, Welcome & Co., of London, 
these having proved to be the most active and least 
disagreeable of all the preparations of thyroid which 
I have employed. He was given three a day, but this 
number caused a rise of temperature and a rapid ac- 
tion of the heart, and hence the dose was reduced to 
two daily. During the following month his progress 
was very rapid, and the change in his appearance 
was extraordinary. All the symptoms gradually 
disappeared, excepting the pigmentation of the face 6 
and hands; the swelling subsided everywhere, so 
that at the end of the month he was wearing a number 
fifteen collar instead of a seventeen, and all his cloth- 
ing was too loose; his facial expression had altered 
Flg. 2. 
greatly for the better, and was almost like that shown 
in Fig. 2, a photograph taken in September, 1894. 
This photograph shows the remarkable change in the 
general appearance. There has been a correspond- 7 
ing change in his general feelings and in his mental 
capacity ; he is now able to do business of an active 
kind with his usual ability. His voice has become 
natural, he has no disturbance in swallowing or 
breathing, and, in fact, is in his usual state of health. 
Within a month of the beginning of treatment the 
albumin and casts had entirely disappeared from the 
urine,and there was present no evidence of any dis- 
ease of the kidneys. The only unfavorable symptom 
that has been noticed during the course of treatment 
has been a marked effect of the thyroid extract upon 
his heart; the pulse has been persistently rapid and 
irregular, and he has suffered from a sense of weight 
and distress in the region of the heart and dyspnea 
on any exertion. This had never been present until 
the thyroid extract was used. It increased to a 
point of great distress when the thyroid was in- 
creased beyond fifteen grains daily, and it became 
less when the thyroid was stopped. He finds it 
necessary to take three grains of the extract, how- 
ever, as, if he stops for more than two weeks, his 
symptoms begin to return. The distress did not 
appear to be very much affected by heart-stimulants 
and by strychnin, which were administered from time 
to time with a view of correcting this depressant 
action of the remedy. It is, of course, necessary 
for him to continue indefinitely the use of the thy- 
roid extract, as this supplies to his blood an ele- 
ment, the absence of which produces all his symptoms. 
The general appearance of patients suffering from 
myxedema—their cachectic look, yellowish color, 
and swollen faces and extremities—suggests to the 
ordinary observer a condition of nephritis. When 
the history of gastric distress and indigestion, of 
general malaise and fatigue on slight exertion, of 
headaches and mental incapacity, of insomnia, and 8 
of general edema is heard, the first suspicion is 
likely to be strengthened. And when the examina- 
tion of the urine shows albumin and hyaline 
casts it seems as if the diagnosis of chronic nephritis 
was perfectly certain. I have made this mistake 
myself in two cases, and have known it to be made 
by some of the most accurate diagnosticians in this 
country before myxedema became as familiar as it 
is at present. Yet unless a physician has examined 
and studied patients suffering from myxedema he 
may be quite liable to this error, and hence I desire 
to call particular attention to the points of differ- 
ential diagnosis between myxedema and chronic 
nephritis. 
In the first place, we need to remember that 
edema occurs under two forms of nephritis in very 
different degrees, i. In the acute form of nephritis 
with scanty urine of high specific gravity, large 
amounts of albumin, and many casts, when all the 
general symptoms are intense and convulsions are 
imminent, the edema is usually extreme. The face, 
body, arms, and especially the legs, are much swol- 
len and pit upon pressure, and it is evident that the 
edema is governed not a little by gravitation, for it 
is more extreme in the dependent parts of the body 
—the feet, ankles, and legs, if the patient is up and 
about; in the back, if he is in bed. Now in myxe- 
dema, even when the swelling is very marked, it has 
characteristics entirely different from those just de- 
scribed. It affects the forehead as well as the face, 
it is as intense in the upper eyelid as in the lower, 
it never fails to cause a thickening of the bridge of 
the nose, and of the lips and tongue. In all these 9 
respects it differs from the edema of nephritis. It 
is more intense over the masseter muscles and in 
the supra-clavicular spaces than anywhere else, form- 
ing pads of soft tissue almost like lipomata. These 
spaces are not often swollen in nephritis. It affects 
the surface of the body quite uniformly, but is more 
noticeable on the abdomen than on the back, no 
matter what the position habitually assumed. Nor 
is it all affected by gravitation. The legs are uni- 
formly swollen all the way down, not particularly 
about the ankles or tibia, and the hands and arms 
are quite as much affected as the feet. The very 
soft parts about the genitals are not excessively 
swollen, as in nephritis. In fact, as a rule, the ex- 
treme swelling in myxedema is usually in the face 
and neck, and not in the feet and legs—just the 
reverse of the condition in nephritis. Finally, in 
myxedema there is no pitting upon pressure, and no 
evidence that fluid beneath the skin can be dis- 
placed by manipulation. Aside, then, from the fact 
that the the slow onset and gradual course of a case 
of myxedema contrast markedly with the acute and 
severe symptoms of acute nephritis, it is possible by 
an examination of the edema to differentiate be- 
tween these two diseases. 
2. But there is another form of nephritis that pro- 
duces edema, viz., chronic nephritis with contracted 
kidneys, hypertrophied heart, and increased arterial 
tension. This is the form with which myxedema 
is most frequently confounded. An excessive 
amount of urine of low specific gravity, scanty 
traces of albumin, and a few hyaline casts are com- 
monly observed in both diseases. In both the 10 
symptoms are of slow progress; in both cerebral 
and gastric symptoms are prominent; and in both 
the pallor and yellowish tint of the skin are known 
to occur. Here again it is to be remembered that 
the edema is entirely different in the two dis- 
eases. In chronic nephritis the edema is not very 
marked, but when it is present it is uniformly no- 
ticed about the ankles after standing, or along the 
tibiae; it never affects the hands and arms; when it 
appears in the face it is under the eyelids, never on 
the forehead, lips, or tongue. In a word, it is 
located in dependent parts of the body, and is de- 
termined by gravitation, or it appears in the parts 
where the normal tissues are loose and where the 
subcutaneous tissue has spaces in which fluid can 
easily collect. The description already given of 
myxedematous swellings contrasts in every point 
with these particulars. Hence, it is evident that 
in the second form of nephritis, in which edema 
occurs, the examination of the patient should suffice 
to detect the differences from myxedema. 
But there are many other points of differentiation. 
I have alluded to the color of the skin and the pallor 
as common to the two diseases. In myxedema the 
skin is remarkably dry and usually in a state of 
active desquamation. The patients have the appear- 
ance of having been recently powdered, and by 
rubbing the surface gently, scaly white particles of 
epithelium are easily brushed off. This condition 
of the skin is certainly not common, if it occurs at 
all in nephritis. 
Again, in myxedema there is no suggestion that 
the skin is unduly stretched, as in ordinary edema, 11 
and it is not thin, and smooth, and flossy. While, 
as a rule, in myxedema the color of the skin is yel- 
lowish-white, all observers have noticed a bright-red 
blush over the cheek-bones, which sometimes gives 
the impression that the patients, who are usually 
women, have been rouged. This high color is not 
seen in nephritis. 
The entire absence of perspiration in myxedema, 
the inability of the patient to get into a perspira- 
tion by any exertion or exposure to heat is another 
symptom not particularly noticed in nephritis. 
The condition of the hair—thin, bristly, coarse, 
and dry—is characteristic of myxedema. Inquiry 
will also usually elicit the fact that from all parts of 
the body where hair appears there has been a marked 
falling of it, so that the patient may be noticeably 
lacking in it; in the axillae or about the genitals, as 
well as on the head. In nephritis the growth of hair 
is not affected. 
Lastly, it is to be remembered that the thyroid 
secretion has an important function in regulating 
the body temperature, and that in myxedema there 
is a uniform depression of temperature, the ther- 
mometer registering only 970 or 97.50 in the mouth. 
Such a condition is not observed in nephritis or 
in any other disease. It is accompanied by a 
subjective feeling of cold, which is one of the 
most annoying symptoms to those who live in the 
North. It is one of the immediate results of the 
thyroid treatment that the temperature rises under 
the use of the extract. I have tried the extract in 
other diseases, and have never seen it produce this 
effect excepting in cases of myxedema. In cases of 12 
akromegaly, in which it seems to have a beneficial 
effect, it does not cause any elevation of tempera 
ture ; and in a case of megalocephaly, in which it 
was very thoroughly tried to the extent of ten tab- 
lets daily, it had no such effect. It is by watching 
the temperature and the pulse that the proper dosage 
of the extract is to be determined in each case. It 
is better to begin with small doses, one tabloid (5 
grains) daily, or 10 drops of the glycerin extract 
of Dr. Crary1 daily, and gradually increase the 
amount, than to give large quantities and cause dis- 
agreeable symptoms. In the case here reported the 
cardiac distress caused by the extract was very 
marked, and could not be counteracted. 
While in the case reported there were no mental 
symptoms present, I think it is right to call attention 
to the fact that a considerable proportion of the 
cases of myxedema suffer from hallucinations, from 
great mental depression, from defects of memory, 
and from decided inability to use the mind. Three 
out of the thirteen cases that I have seen were 
brought to me because of the mental symptoms. 
The type of derangement which is present in myx- 
edema is somewhat different from that ordinarily 
seen in mental diseases. While there is a depression 
and a decided melancholic tendency, there are very 
rarely any delusions, and never the typical facial 
expression of melancholia; nor are there intercur- 
rent periods of mental depression and self-accusa- 
tion which often occur in melancholia. The patients 
do not wake early in the morning with the intense 
depression that is seen in that disease. In melan- 
1 New York Medical Record, June 17, 1893. 13 
cholia hallucinations are exceedingly infrequent, 
while almost all myxedematous patients when af- 
fected mentally will describe hallucinations of sight 
and, sometimes, of hearing, occurring frequently at 
night; animals and faces are seen, and voices are 
heard, yet, as a rule, these hallucinations are recog- 
nized as products of the mind ; they are not firmly 
believed in, and they do not become the cause for 
excitement as in hallucinatory insanity. 
The prevailing mental tendency in myxedema is 
toward a demented condition; the patients are 
stupid, dull, sit listless, doing nothing, prefer to be 
left alone, take no interest in their surroundings, 
and appear to be lacking in all spontaneous mental 
processes; yet even this form of dementia differs 
decidedly from the primary dementia or the termi- 
nal dementia of insomnia, for the patients can be 
aroused to thought, show few defects when excited 
to mental action, and none of the incoherence of 
speech which betrays a mind permanently shattered. 
The entire disappearance of all these mental symp- 
toms is one of the gratifying results of the treatment 
with thyroid extract. The three patients to whom 
I have alluded remain in a state of mental as well as 
physical health so long as they continue to use the 
extract. It is not at all improbable that a careful 
search in the asylums of this country would result 
in the discovery of a number of cases of myxedema 
now supposed to be instances of chronic dementia, 
but really capable of cure. The Medical News. 
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