Cases of Myxoedema and Acromegalia 
Treated 'with Benefit by Sheep's 
Thyroids: 
Recent Observations Respecting the Pathology of the Cachexias 
following Disease of the Thyroid; Clinical Relationships 
of Graves's Disease and Acromegalia. 
BY 
JAMES J. PUTNAM, M.D., 
OF BOS1ON. 
FROM / 
THE AMERICAN JOURNAL OF TJ4E MEDICAL SCIENCES, 
August, 1893. Extracted from The American Journal of the Medical Sciences, August, 1893. 
CASES OF MYXCEDEMA AND ACROMEGALIA TREATED WITH 
BENEFIT BY SHEEP'S THYROIDS: 
RECENT OBSERVATIONS RESPECTING THE PATHOLOGY OF THE CACHEXIAS 
FOLLOWING DISEASE OF THE THYROID; CLINICAL RELATIONSHIPS 
OF GRAVES'S DISEASE AND ACROMEGALIA. 
By James J. Putnam, M.D., 
OF BOSTON. 
Case I. is that of an unmarried lady, now forty-eight years old, and always 
of delicate health. 
I was first called to see her in December, 1885, and at the time of my visit 
the diagnosis was beyond question, even from her appearance alone. 
She had taken cold while menstruating during a visit to the Philadelphia 
Exhibition of 1876, and it is possible that this was the starting-point of her 
sickness, though she was then pronounced only severely anaemic, and the myx- 
cedemic symptoms were not noticed until 1880 or 1881. The family history on 
the mother's side was markedly neurotic. 
The face was clayey-gray, with a yellowish tint, the skin thick, stiff, dry, 
and coarse. The lips were protuberant and thick, and moved each in one 
piece, as it were, as she talked. The eyelids were swelled and alabaster-like 
in appearance, especially the upper, which overhung the eyes so that at times 
she had to throw the head back a little in order to see. The neck was thick, 
the hands were large, scaly, and dry, and a similar dry and coarse condition of 
the skin was everywhere present. 
The nutrition of the teeth and nails was defective, and the hair had fallen 
out except for a few bunches here and there. 
Formerly slender and with delicate coloring, she now looked overgrown and 
old. The limbs were large but not strong, and the skin was so inelastic and 
so tightly stretched over the legs below the knee, that the masseuse found it 
impossible to use the ordinary methods of manipulation. No true oedema was 
noted at this time, but at a later period the ankles pitted deeply on pressure. 
The swelling of the eyelids was partly watery, and increased during the night 
toward the side on which she lay. 
The pulse was but 60 ; the heart-sounds free from murmur, but exceedingly 
feeble. There was a tendency of the head to droop forward, so that it was 
with an effort that she held it erect. The voice was husky and the tongue 
thick. The gait was slow and insecure, so that she often stumbled and some- 
times fell. She felt weak, and became breathless on slight exertion. 
The mental condition was no less striking than the physical. An incon- 
querable inertia and apathy imprisoned her thought, feeling, and action, so 
that she could neither plan nor execute effectively, and every trifling duty 
seemed a mountain to climb; and yet her ineffectiveness did not fill her with 
real despondency. 
Her friends would leave her with one boot on and the other in her hand, 
and return an hour later to find her in the same condition and attitude. Or 
what she held would slip from her grasp and she would not stoop to pick it 
up. Or, at times, she would lean in a stupor against the .mantel-shelf, and 
remain motionless for one or two hours. The nearest duties often passed un- 
fulfilled, and the thought of them failed to rouse her. Yet in spite of her 2 
PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
slowness, and lethargy, and lack of initiative, she was neither melancholic 
nor demented, and would converse intelligently and pleasantly, though 
without animation, on many subjects. It is interesting to note (see below) 
that a certain degree of this apathy and slowness was characterstic of her 
temperament even many years before her illness began. 
She slept all night, though often troubled with distressing dreams, but 
was constantly drowsy in the day. She suffered much from constipation, 
and later from hemorrhoids, and had an offensive expectoration, which no 
doubt contributed to give the breath the cadaveric odor which then charac- 
terized it. 
The menstruation was at that time regular, but profuse; later it became 
very irregular, and was absent for months together, and her periods would 
leave her much weakened. 
The urine was habitually very pale, and of low sp. gr„ free from albumin 
and sugar. All the solid constituents were diminished, the amount of urea 
being 11.78 grm. to the litre (Prof. E. S. Wood). 
The thyroid could not be felt. The skin was cool to the touch ; and the 
temperature usually ranged around 95° F. Several times it almost touched 
94°; and 97° was rarely, if ever, passed, even in slight sickness. 
Blood-counts made during March and April, 1886, showed 3,120,000; 
3,200,000; 3,234,000; 4,240,000. The proportion of whites was normal. 
The next four years brought little change, except that in winter she would 
be worse, in summer better. 
In the summer of 1891, however, a new symptom showed itself, namely, 
a synovitis with great external swelling, first of one knee, then of the other, 
brought on by a trifling shock or wrench, due to stepping heavily, the first 
time out of a carriage, the next time out of a horse-car. In one of the cases 
reported very early by Dr. Ord, the rupture of both patella tendons occurred 
in a similar manner, and the excessive swelling has been several times ob- 
served. The synovitis ran a very indolent course, and the appearance of the 
knee, with its thickened tissues, was so peculiar as to suggest the presence of 
some other process than simple effusion. 
Up to the 1st of June, 1892, no treatment had brought material benefit, 
though persistent massage had given the patient much comfort. In June, 
1892, I began a series of tri-weekly injections of a glycerin and carbolic 
extract of the sheep's thyroid, prepared as recommended by Dr. Murray. 
Slight signs of improvement began to show themselves by the end of one 
or two weeks. In the course of six weeks the improvement in color, strength, 
and manner attracted the attention of everyone who knew her, even the 
children of her neighborhood, and was further confirmed by the appearance 
of a growth of fine hair all over the head, and a marked rise in pulse and 
temperature. 
The temperature varied, but by the end of August, perhaps earlier, it 
ranged pretty constantly between 96° and 97° F. Menstruation, which had 
been absent so long, recurred in July, August, and September, but such recur- 
rences had occasionally showed themselves, and it was still profuse and 
painful. 
The swelling of the eyelids varied in amount, but during August it was 
almost absent, and that of the ankles had greatly lessened. 
With the advent of the colder weather of September and October, I saw with 
regret that her improvement, hitherto steady, seemed to have suffered a check. 
She began to look pale and to feel languid, the swelling of the eyelids reap- 
peared, and she complained of pain in the chest on slight exertion. Attribut- 
ing this in part to an interruption of the treatment during the first ten days 
of October, I tried giving the injections more frequently than ever, part of the 
time almost daily, though at first without marked effect. 
In November she began the treatment by the mouth, as recommended by 
Mackenzie and by Howitz, of Copenhagen, and took five or six sheep's thy- 
roids a week (or more strictly, five or six lobes, as the sheep's thyroid consists 
of two separate lobes). 
During the next month, and even after the final stage of improvement PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
3 
had been fairly entered upon, she complained much of a sense of thumping 
in her head, and while her mental condition was becoming steadily more 
natural, her appetite and strength seemed for a time rather to fail. 
Ever since the outset of the treatment, she had noticed at times a sense of 
flushing and dizziness after the injections, such as has been noted in the re- 
ports of some of the English cases, but neither this effect nor the increased 
secretion of urine which others have noted was at all striking. 
On December 9th, an estimation of the haemoglobin by Fleisch's apparatus 
gave 55 per cent. Toward the end of December there was another period of 
depression in which she complained of increased thumping in the head and 
ears, and of nausea and languor, especially in the morning. These symptoms 
seemed at least partially attributable to an excess of thyroids, of which she 
had taken four glands a week, though these periods of depression did not 
invariably attend the use of the larger amounts. 
This sense of illness was, however, attended by a rise of pulse and tempera- 
ture rather than a fall, the pulse reaching 78 on December 18th, and the 
temperature 98°. And furthermore, it was plain that the whole character of 
her nutrition was becoming more normal, though it was not in all respects 
satisfactory. On December 21st, when I had not seen her for nearly Jhree 
weeks, it was evident at the first glance that the condition of myxoedema was 
giving place to one of simple anaemia. She complained a great deal at this 
time of itching, which others have noticed likewise, perhaps from the action 
of the thyroids, but more probably from the changes taking place in the 
skin. 
It was difficult to say whether she had actually grown paler or less pale, 
so unlike was her present complexion to that of the clay-like mask that she 
had worn so long. Unfortunately, she could not easily be weighed, but it 
was clear that she was rapidly growing thinner and slenderer, while her hands 
were becoming softer and more shapely. The clothes that she had worn were 
now hanging in folds, and in fact she became at this time really too thin, and 
with still further improvement she has gained flesh somewhat. 
The opening of the new year was marked by her discarding her wig in favor 
of her new growth of dense and soft hair (now about four inches long) and 
by her beginning to take the thyroids in the form of powder, skilfully pre- 
pared by Parke, Davis, & Co., at my suggestion. 
I had been in correspondence with them for this purpose for a number of 
weeks, and did not learn until later that similar methods were being adopted 
in Sweden and England. Fifteen grains of this powder represents one lobe of 
a sheep's thyroid. The taste is found nauseous by some patients, and does not 
disappear for many hours. These objections are mainly obviated by the use 
of capsules, or of keratin-coated pills, which do not dissolve in the stomach. 
Not only had her face and figure by this time changed so that acquaint- 
ances occasionally failed to recognize her, but her voice had grown markedly 
firmer and clearer, and her manner alert and responsive. 
An accurate examination of the blood made by Dr. J. J. Thomas gave the 
following result: 
Reds . . 5,700,000 f Polynuclear whites 66.4 per cent. 
„ AAA j Mononuclear " . 21.6 " 
White . . 7,000 Lymphocytes. . 10.04 " 
Haemoglobin 61 per cent. I Eosinophiles . . 2.0 " 
No increase in size of reds. A few myelocytes. 
The menstruation recurred normally and almost painlessly in January, 
February, and March and April, appearing exactly at the expected date. 
For two weeks in February and March she took no thyroids, and toward the 
close of that time there were signs of a recurrence of symptoms, a firm non- 
oedematous swelling appearing in the legs above the ankles. The mental 
condition remained good, and on resumption of the thyroid powders the 
slight swelling soon disappeared. 4 
PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
Since the treatment was begun, the neck, waist, and arms have diminished 
about three inches in girth, and the old shoes and gloves have, so to speak, 
discarded themselves. She is still an anaemic and delicate person, as she 
always was, but as regards any distinct myxoedema she is practically well.1 
The temperature is usually normal, but occasionally runs half a degree too 
low. 
Case II. is that of a lady fifty-five years old, and is particularly interest- 
ing, both because the improvement was very rapid, and from the fact that 
previous to the onset of the myxcedematous symptoms, the thyroid was much 
enlarged, and moderate but constant tachycardia was present. The patient 
has been under the care of another physician, and I have seen her only in- 
cidentally except during the first period of the disease, when I tried for 
some time to reduce the size of the goitre by electrolysis. The case is also of 
interest from the fact that the patient's cousin and aunt had myxoedema in 
a pronounced form, and eventually died with it, the latter as an elderly per- 
son, the former in middle life. The aunt had been for many years crippled 
with rheumatoid arthritis. 
The case seems to be one of those where an exciting cause of the disease 
may well have been anxiety and emotion, acting on an intense and sensitive 
temperament. The thyroid first began to enlarge about ten years ago. The 
tumor was unusually hard, much harder than the normal gland, and there 
were no vascular murmurs such as are often seen in Graves's disease. There 
was no exophthalmus, but the pulse was always moderately rapid-from ninety 
to one hundred and twenty. In view of the important question as to the 
possible relationship between Graves's disease and myxoedema, it is interesting 
to bear in mind that we have here a case where in the presence of a manifestly 
hereditary tendency to myxoedema, the first actual change was this thyroid 
disease, with at least one of the Graves's disease symptoms. (Perhaps, how- 
ever, the tachycardia was purely reflex. See below.) 
It is also a noteworthy fact that the patient's health failed considerably 
during the first period, and that besides dyspnoea, which may have been due to 
pressure, she suffered much from anaemia and debility. As her health had 
previously been good it is reasonable to suspect the thyroid disease as having 
been responsible for the falling off at this period, the more so that with the 
recent thyroid treatment not only the myxoedema but also the anaemia has for 
the most part disappeared. The myxcedematous changes first showed them- 
selves two years ago, at the time of the menopause, and have been unmistak- 
ably characteristic ; the presence of the alabaster-like swelling and pallor of 
the eyelids, lips, and face, the dryness of the skin, the increased size of the 
hands, the gross enlargement of the body, slightly subnormal temperature, 
thickness of the tongue, and slow speech leaving no doubt as to the diagnosis. 
The urine contained a trace of albumin, and occasionally a few casts. Mental 
changes have not been present. 
The treatment with the thyroid powder was begun about February 15th, 
since which time the patient has taken one powder of fifteen grains, which 
is the equivalent of one lobe of a sheep's thyroid, every second day. 
The improvement was more rapid than in the first case, perhaps because 
the disease was less advanced and because the patient's previous health had 
been better. There is still some swelling of the legs, with ordinary cedema, 
but the patient's face has regained its delicacy and size and color of fifteen or 
twenty years ago. The thyroid is still large, though not so large as before. 
It will be very interesting to follow the condition of the urine in order to see 
whether the renal changes disappear. At present casts are still to be found, 
though they were absent in the three or four examinations made during the 
year previous to the beginning of the treatment. 
1 An examination of the blood made since this paper was written has shown that 
the anaemia has not improved of late, but rather grown severe, though in other re- 
spects the patient is doing well. PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
5 
I have also notes of three other patients who are taking the thyroids 
with benefit. One of them has acromegalia of rapid onset and typical 
form. No enlargement of the jaw is present, but the big hands and 
feet, rapid pulse, with tendency to palpitation and moderate muscular 
atrophy, place the diagnosis beyond question. 
She came first to the out-patient department of the Massachusetts 
General Hospital, and was seen by Dr. G. M. Garland, who kindly 
gave me the opportunity of examining her. Later, she entered the 
wards, in the service of Dr. F. C. Shattuck, and there she improved 
somewhat under tonic treatment and sodium salicylate. 
Some weeks after her discharge, however, I looked her up and 
found her still feeble and unable to work. Under fifteen grains 
of the thyroid powder every second day she has gained steadily, so 
that now, at the end of three weeks, she works with her hands for 
two hours daily. 
Of the other two cases, one stands nearer to acromegalia, the other 
to myxoedema, though in both the diagnosis is doubtful. The latter 
is of especial interest from presenting atrophy of the optic nerves, 
which is more common in acromegalia than in myxoedema, though 
seen in the latter disease (Hun and Prudden, Wadsworth, Jones). 
The former is under the care of Dr. G. C. Stearns, of Leicester, but 
is taking thyroids at my suggestion. A letter received yesterday 
reports that the improvement goes steadily forward, both as regards 
general strength and the appearance of the face and lips. 
There is a large swelling of the neck, probably a thyroid, which 
is diminishing in size under treatment; and, in fact, both patients 
consider themselves as decidedly better. 
There are many questions of detail with regard to the new treat- 
ment by thyroid preparations which are of great practical impor- 
tance. The following seem to me especially so : 
Is the method by the stomach equally effective with that by injec- 
tion, and is there anything to choose between the powder prepared 
by evaporation, the gland itself, and the extract precipitated with 
alcohol as recommended by Vermehren? 
Must the dose by the stomach be larger than that by injection, and, 
if so, for what reasons ? 
What is the cause and significance of the rapid loss of weight so 
often noted, and may it occur in ordinary obesity, or with healthy 
persons, under the use of thyroids ? 
What is the cause and significance of the other symptoms observed 
during the thyroid treatment, especially those of cardiac origin? 6 
PUTNAM: FEEDING THYROIDS IN MYXfflDEMA 
Are signs of renal irritation brought on or increased, and under 
what conditions ? 
Some of these questions can already be answered fairly well. The 
method by the stomach has not failed in any genuine case, and 
although one of the best of English observers at one time asserted 
that four or five times as large a quantity must be given to get the 
same effect as by subcutaneous injection, yet moderate quantities are 
sometimes so effective that we have no reason to conclude that any 
considerable part of the dose passes uuabsorbed in most conditions 
of the stomach and intestine. Some good chemical or physiological 
test is, however, much needed to enable us to study these points 
and to compare the different preparations. 
The loss of weight is an early sign of improvement, but it some- 
times goes beyond the requirements of health ; and this fact, coupled 
with the observations of Dr. A. Barron, of Liverpool, on the effects 
obtained in obesity,1 suggests that the thyroid secretion may, under 
certain conditions, modify the tissue-changes even of healthy 
persons. A myxoedematous patient of Laache's lost more than 
nine kilogrammes, or about nineteen pounds, in three weeks, and 
my first patient must, at one time, have lost weight almost as 
rapidly. 
Immediately after the injections, and even the stomach doses, of 
thyroid, there is sometimes a rise of temperature and pulse, increased 
secretion of urine, faintness or headache, and other symptoms; as 
the treatment goes on these symptoms may continue for a time, and 
may be associated with prostration, cardiac weakness ; anginoid, 
neuralgic, or other pains (Laache), and even albuminuria (Laache). 
(Note also the increase in signs of renal irritation in my second case.) 
It is striking and important that these unpleasant signs sometimes 
last for weeks after the suspension of the treatment. 
Dr. F. C. Shattuck will no doubt call attention to an important 
case which he kindly asked me to see with him, where attacks of pal- 
pitation with anginoid pain continued for several weeks after the 
cessation of a rather active, though short, course of treatment which 
had in other respects been remarkably effective for good. The fact 
that these effects last so long after the treatment by thyroids has been 
stopped, and that, on the other hand, they have failed to appear in 
1 Dr. Barron has very kindly written to me that he has used the treatment in five 
cases of ordinary corpulence. One lost twenty-eight pounds in six weeks, three a 
moderate amount, and all lost more or less. I am trying it in two typical cases, but 
have no results to report as yet. PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
7 
some cases where large doses have been given, or at any rate do not 
necessarily appear at once (Vermehren) (my first patient has taken 
repeatedly thirty grains of the powder without noticeable effect), 
render it unlikely that they are wholly due to a direct action of the 
thyroid extract regarded as a drug. At any rate, other explanations 
suggest themselves as more probable. 
One is that through an increased excitability of the cardiac centres, 
or from some other cause, the heart is called upon for increased action 
at a time when its muscular walls are in an abnormal state, or when 
its coronary arteries, which are liable to be thickened, are not supply- 
ing it with sufficient blood; another, that the products which are 
absorbed so rapidly from the diseased tissues act as irritants. It will 
be remembered that two of Murray's cases died while their improve- 
ment was in full progress, from sudden heart failure brought on by 
trifling exertion. One of these patients was known to have had 
cardiac disease, the other was assumed to have had a fatty heart. 
At any rate, the action of the thyroid extract is not in all respects 
the same in health as in cases of myxoedema. Fenwick finds that 
diuresis does not occur in health, nor usually with myxoedematous 
patients unless they are under some slight excitement. 
As regards the question of renal irritation, I would call attention 
to my second case, where, in spite of rapid improvement in other 
respects, the number of casts in the urine increased, and to Laache's 
case in which temporary albuminuria came on. 
In another case, recently reported (Holman) the urine during 
treatment contained very large quantities of mucus. 
Before leaving this part of the subject it must be noted that not 
only have the cases of myxoedema, successfully treated by animal 
thyroids, been gathering like a rising tide, but that myxoedematous 
cretins have likewise been shown to be susceptible of a considerable 
degree of improvement (Bramwell, Affleck, Carnwick, Gibson). 
The point has not attracted as much attention as it deserves, that 
the "directly" haematopoietic functions of the thyroid, if they are 
of real importance, ought not to be met by ingestion of the thyroid 
secretion. 
As a matter of fact, the anaemia of my first case does not seem 
inclined to pass away with the myxoedematous symptoms. 
I shall confine rayself, in what follows, to the pathological side of 
the subject. 
To indicate, for reference sake, the percentage of frequency with 
which the different organs are diseased, I have arranged the results 8 
PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
of the post-mortem examinations, including those published since 
1888, in the form of a diagram, which, of course, must be taken as 
having only a relative and provisional value, since the autopsies are 
few, and the observations often incomplete and probably inaccurate. 
I am not tempted to refer in detail to the varied anatomical 
changes to which the different organs are liable, because so little that 
is of fundamental importance has appeared since the able paper of 
Hun and Prudden and the report of the Committee of the Clinical 
Society of London in 1888, and especially since the masterly review 
of the functions of the thyroid by Horsley in 1890. Two experi- 
mental researches are, however, worthy of special mention. One is 
that of Hofmeister, who removed in young rabbits the main part of 
the thyroid, but not the glandules of Gley. This is supposed to 
leave the rabbits practically uninjured, and, indeed, their health does 
not apparently suffer, though the hair is apt to become a little coarse 
and the body relatively short and thick. 
In fact, however, a series of other changes occur. The growth of 
the bones is checked ; the epithelium of the convoluted tubules of the 
kidney is altered ; the ovaries undergo a premature ripening, with an 
immense development of follicles. The hypophysis cerebri enlarges, 
but the spleen and thymus do not, and no histological changes were 
found in the central nervous system or in any of the abdominal 
organs. 
The second research is by Capobianco, of the University of Naples, 
and has reference to the condition of the nervous system in the acute 
stage of the cachexia after thyroidectomy in dogs. They are fully 
confirmatory of the older observations of Rogowitsch, and show 
clearly how profoundly the circulation and nutrition of the brain, the 
medulla, the cord, and the nerve roots may be altered. The fact that 
other observers have found only circulatory changes, with oedema 
(see Horsley's paper) or swelling of axis cylinders (Kopp), shows 
that there are great differences in the degree to which these results are 
produced, but for this very reason we should scrutinize carefully before 
giving the verdict, " normal " ; and the more so when we recall that 
changes in the electrical irritability of the cortex cerebri (Schiff, 
Horsley) and the peripheral nerves (Awtokratow, Schwartz) are 
found. 
The discovery by Hodge, of Clarke University, that simple fatigue 
leaves its mark on healthy nerve-cells-even physiological fatigue, as 
that of bees after their day's flight-should be borne in mind in this 
connectiou. Not only do these observations show the possibility of PUTNAM: FEEDING THYROIDS IN MYXOEDEMA. 
9 
recognizing slight changes in nucleus and protoplasm, but they point 
out-what is too little regarded-that in estimating the effects of 
poisons or of other causes of impaired nutrition upon the central 
nervous system, we ought to know what conditions as regards exer- 
tion and fatigue had been present shortly before death. A man or 
animal who has taxed his poor or poisoned nervous centres will 
certainly have induced histological changes that otherwise would be 
wholly absent, and the exertion necessary for this result may be an 
amount which would ordinarily appear trifling. 
It would be extremely interesting to see Hodge's experiments 
repeated on animals with the cachexia thyreopriva. The probability 
that positive evidences of an increased liability to fatigue would be 
found is foreshadowed by the experiments of Manfredi Albanese, 
which point to an increased susceptibility to fatigue on the part of 
the spinal cord in the serious condition which follows removal of the 
supra-renal capsules. 
No doubt the case is different for the chronic stages of myxoedema 
and cretinism. 
We do not know about liability to fatigue, but no histological 
changes were found, at any rate, by Hofmeister in his rabbits, or by 
such careful observers as Hun and Prudden in their cases of myxoe- 
dema. There are no histological changes, indeed, that are distinctly 
characteristic of the nervous centres of cretinism (Bourneville), though 
the arrangement of the convolutions is often peculiar. 
Langhans and Kopp have made a careful study of the peripheral 
nerves after thyroidectomy and in cretinism, and have found a series 
of interesting and peculiar alterations in the endothelial cells of the 
perineurium and endoneurium, as well as in the lymph spaces and the 
bloodvessels, arranged in minute foci here and there, especially in the 
nerves. The paper is one for histologists to discuss. Langhans at 
first thought these appearances to be peculiar to goitrous diseases, but 
this is very doubtful (Schultze, and Langhans himself). 
The blood presents no constant changes except those of acute 
anaemia, and in the acute stages increased venosity (y. Horsley). 
The red cells have been found larger and also smaller than normal; 
the proportion of whites increased and normal; eosinophiles in- 
creased in one case (Ehrlich); myelocytes present in one (Case I.). 
As to the final cause and nature of the changes which constitute 
myxoedema and cretinism, that is a riddle the solution of which we 
can approach bub-cannot reach. That the blood becomes toxic is 
inherently probable, and is confirmed by the fact that although 10 
PUTNAM: FEEDING THYROIDS IN MYXEDEMA. 
usually harmless1 if transfused into healthy animals, it precipitates 
the cachexia in the case of animals deprived of their thyroids (Fano, 
Zander, Rogowitsch, Fuhr); while, on the other hand, the cachexia 
may be mitigated by the infusion of healthy blood. Gley asserts 
that the toxicity of the urine is also increased. 
The skin, the kidneys, the ovaries (Hofmeister, Langhans), the 
liver, the heart and pericardium, and other organs and tissues, also 
show signs of irritation and sometimes of degeneration. This is doubt- 
less sometimes mucinoid in character, but mucin has not always been 
found, even in the skin, and Jurgens shows how complex the change 
which we call mucinoid really is. We do not yet know whether 
mucin, when it does occur, is merely a sign of degeneration or 
whether it is itself a poison. That it is the chief or only poison in 
myxoedema is highly improbable. 
There are, moreover, some phenomena which seem to be less easily 
explained as the result of irritation and degeneration than as evi- 
dences of a sort of variation in structure, analogous, perhaps, to that 
which follows castration. 
The curious fatty tumors of the neck so characteristic of myxoe- 
dema and myxoedematous cretinism are not easily accounted for as 
results of irritation; the changes in the ovaries of Hofmeister's rab- 
bits were interpreted by him as a sign of follicular hypertrophy or 
premature ripening ; the myxoedematous cretin is not only a diseased 
and degenerate individual, but may be regarded as a different variety, 
and this appears even in his mental characteristics. 
If one looks for other instances of alteration of type with which 
to compare this, the most striking and, possibly, the nearest is that 
of eunuchism from castration, by which the bull is changed to the 
ox, and the cock to the capon. The analogy would be more sig- 
nificant if it could be shown by experiment that the effects of castra- 
tion could be prevented by frequent injections of testiculin ; indeed, 
the analogy would not hold if the results of this experiment turned 
out negative. So far as I know, it has never been tried, but it seems 
to me a reasonable experiment, and a logical outcome of the suggestive 
observations of Brown-S6quard and D'Arsonval. 
The next point to which I wish to call your attention is with 
regard to the incomplete or partial forms of the thyroid cachexias. 
The attention of physiologists and pathologists has hitherto been 
mainly directed to the study of the diseases due to complete, or nearly 
1 Gley finds the blood of dogs after thyroidectomy to cause convulsions in rabbits. PUTNAM : FEEDING THYROIDS IN MYXOEDEMA. 
11 
complete, destruction of the thyroid; and the opinion is current that 
the functions of the gland may be as well performed by a part as by 
the whole, because it has been found that when a piece of any con- 
siderable size is left, the cachexia does not, as a rule, occur. Usually 
the remaining piece grows larger. Sometimes the accessory gland- 
ules, which are ordinarily embryonic in character, also increase 
in size, and probably in efficiency, though they never grow to the 
size of the original gland. A compensatory enlargement of the 
hypophysis cerebri may also, it is thought, occur. 
An additional argument that a part of a thyroid will serve for the 
whole is apparently furnished by the recent experiments of Beresow- 
ski. He removed enough of the gland to cause cachexia, and found 
that in the course of a few days distinct processes of repair had set 
in, as indicated by karyokinetic division of the glandular epithelium. 
This hyperplasia ceased, however, long before the piece of the thyroid 
had reached the full size of the gland, and the reason for this was sup- 
posed to be that the vital needs of the gland had been met. 
In spite of the large amount of truth in these generalizations, it is 
in order to inquire whether we really have sufficient grounds for 
believing that the thyroid is so unnecessarily large, and, if this is not 
the case, whether we may not learn to discover and relieve diseased 
conditions associated with a partial destruction of the gland. 
It is important to note, as indicating the complex nature of the 
problem, that myxoedema may fail to occur even when the true 
glandular epithelium of the thyroid has been replaced by a cubical 
variety, apparently secreting no colloid; and, indeed, a small part of 
a gland so altered may suffice. This is illustrated by the history of 
a case of Graves's disease reported further on in this paper, and by 
the experiments of Halsted and Welch upon dogs. 
As regards the argument drawn from the cessation of the com- 
pensatory hypertrophy at a certain point, it seems to me extremely 
improbable that the amount of regeneration is exactly proportional 
to functional requirements. The law of repair is more complicated 
than this, and that is indicated in the present case by the fact that 
Ribbert found a true regeneration to follow the removal of compara- 
tively minute pieces of the thyroid (see also Neumeister). 
It would be an interesting research to see how much, or rather 
how little, of the thyroid must be removed before changes in growth 
and nutrition can be detected, especially in the light of Hofmeister's 
experiments, which show that rabbits may present them in spite of 12 
PUTNAM: FEEDING THYROIDS IN MYXffiDEMA. 
retaining, by the aid of their carotid glandules, apparently good 
health. 
The studies of dosage during the treatment of cretinic children 
by sheep's thyroids, will no doubt throw much light upon this matter 
of the amount of thyroid secretion needed for full compensation, and 
meantime some clinical evidence is already forthcoming to show that 
the amount of thyroid sufficient for life, and fair health, is not neces- 
sarily sufficient for all the functions of the gland. 
Some of the most important forms of cachexia from thyroid dis- 
ease, not severe enough to cause myxoedema, are the following: 
1. The early history of myxoedematous patients sometimes gives 
evidence of the presence of analogous forms of degeneration. 
Two cases have been reported within a few years (Loewy, Merk- 
len), where myxoedema came on when the patients were between 
twenty and thirty years old ; yet both were of dwarf-like stature, 
and presented certain slight mental peculiarities which, without 
stamping them as cretins, suggested a congenital deficiency of thyroid 
action. 
Struck by these cases, I turned to the abstracts published by the 
Committee of the Clinical Society to look up the early history of the 
patients who became myxoedematous before their twentieth year; that 
is, cases of myxoedema belonging to the period antecedent to senile in- 
volution, and I found these histories, incomplete though they are, to be 
of much interest. Four such cases are recorded, and in at least three 
of them, in spite of the scanty record of antecedents, there had been 
signs of degeneration, such as very low bodily weight; slight mental 
weakness; small, broad, and depressed nose; and extremely large 
tongue, indicating, perhaps, as in the cases first cited, a partial and 
unrecognized cretinoid state existing since childhood. 
It is noteworthy that my first patient was not only anaemic and 
lacking in robustness, during her early life, but also showed some 
degree of the lethargic temperament which afterward became so very 
marked. 
2. Cretinism is a disease of many degrees, and some of the cretins 
show a fair intelligence, a few a first-rate degree (comp. Bircher, and 
a celebrated case cited by Langhans). Yet their skulls are of the 
type now considered as probably, or possibly, characteristic of thy- 
roid disease. In myxoedematous cretinism, which is the lowest 
type, characterized by unossified fontanelles and synchondroses (occa- 
sionally premature ossification), dwarf-like stature, tendency to um- 
bilical hernia, etc., the thyroid is greatly atrophied, sometimes absent. PUTNAM: FEEDING THYROIDS IN MYXOEDEMA. 
13 
In other forms the atrophy is only partial (Hanau), and portions of 
he gland may look healthy. Furthermore, the removal of a cretinic 
thyroid may cause myxoedema (Bircher). 
3. Goitrous persons, in districts where the disease is endemic, are 
generally of inferior type, though, of course, it is not certain that the 
thyroid disease is the cause of this. 
In my second case, which is probably typical of others, it is 
worth considering whether the anaemia and debility of the pre- 
myxoedematous, but goitrous, period may not have been an early 
stage of thyroid cachexia. 
At any rate, myxoedema sometimes comes on quickly, but oftener 
slowly, and in the future it will be of great importance to learn to 
recognize the preliminary symptoms. 
Another fact, of which we should never lose sight, is that myx- 
oedema, or tetany, and perhaps other signs of the thyroid cachexia, 
may follow temporary disease of the thyroid, from which the patient 
eventually recovers, and may then pass away. Not only does this 
happen after partial thyroidectomy, but in the course of syphilis 
(Kocher), and as a result of ordinary goitre (v. Horsley's paper, 
1890, Brit. Med. Journ., 1890.) 
As regards the question of the compensatory hypertrophy of the 
hypophysis, it is certainly true (Rogowitsch, Stieda, Hofmeister) 
that thyroidectomy done on dogs and rabbits is usually followed by 
enlargement of the hypophysis, which comes so near the thyroid in 
structure and origin, and it would seem also that the thyroid may 
enlarge after removal of the hypophysis (Vassale and Sacchi). On 
the other hand, it is not accepted as certain that this enlargement 
means increase of functional activity. 
To express a complicated matter in a few words, it is generally 
conceded that the hypophysis contains two kinds of cellular bodies, the 
" chromophiles," and the Hauptzellen (Stieda and Rogowitsch), or 
a nucleated protoplasm " (Schbnemann). 
When the gland enlarges there may be found an increase in the 
number of chromophile cells, or an enlargement of the Hauptzellen ; 
and there is almost always an increase in the colloid contents of the 
gland. The increase of the chromophile cells has been thought 
(Lothringer, Arch, fur mikroscop. Anat.; cited by Vassale and 
Sacchi) to be of functional significance; but Schbnemann, on the 
basis of a careful study of the hypophysis of a cretin, came to the 
opposite conclusion, namely, that the chromophile cells are degen- 
erated forms, and are finally to be converted into colloid. 14 
PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
Vassale and Sacchi have recently made an ingenious experiment 
which seems to favor the view of Sehonemann. Removing the 
hypophysis from an ox, they divided it into two parts; and while 
one of these was preserved in alcohol for comparison, to indicate 
the normal histology, the other was introduced into the abdomen 
of a rabbit and left for three days, presumably to undergo slow 
degeneration. The chromophile cells in the latter half were found 
to have increased greatly in number. 
The same observers deny that the mere increase in colloid matter 
ought to be taken as a sign of increased functional efficiency, either 
in the case of the hypophysis or the thyroid, unless it is accompanied 
with indications of active cell-growth of the glandular epithelium, 
with karyokinetic appearances, and this, they declare, does not occur 
in either organ simply from extirpation of the other. They do, 
however, regard the two organs as physiologically similar, and this 
is important for the pathology of acromegalia, which seems to me a 
disease kindred to myxoedema, though .the bond may be but that of a 
Scottish cousinship. 
Hofmeister's experiments, which are especially valuable because his 
rabbits remained alive and well, and the hypophysis was given from 
three to six months in which to show its supposed compensatory 
growth, are confirmatory, as he thinks, of the observations of Rogo- 
witsch and Stieda. He finds, as they did, not only an enlargement 
of the whole organ, but an increase in the size of the Hauptzellen.1 
The question is therefore still open for further research, but here- 
after increased size cannot be taken as a sure sign of increased 
efficiency. 
One suggestion thrown out by Hofmeister is worthy of comment, 
namely, that the large size of the sella Turcica, several times noted 
in cases of cretinism, indicates that the hypophysis had been hyper- 
trophied. Klebs makes the same remark with reference to a case of 
acromegalia. As bony changes are, however, of regular occurrence 
1 There are several reasons for concluding that the colloid is not the important part 
of the thyroid secretion, but an envelope, or a by-product. Even its presence is not 
essential. 
The valuable researches of Halstead and Welch, made some years ago, but not yet 
published, show that in the regeneration of the thyroid which follows mutilation, the 
histological character of the gland may undergo great change. The epithelium tends 
to become high and cubical, instead of flat, and the colloid to disappear. Eventually the 
whole gland may be made to show this change. (See Trans, of the Assoc, of Amer. 
Physicians, 1893. Discussion on Myxoedema.) 
A closely similar change has been noted by Councilman in a case of Graves's disease 
described farther on, yet this patient was not myxcedematous. PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
15 
in both of these diseases, the increased size of the sella Turcica admits 
of a different interpretation, and Schonemann distinctly notes that 
while the sella Turcica of his cretin was large, the hypophysis was 
rather small. Possibly it had been enlarged at an earlier period. 
Certainly the hypophysis is not always enlarged either in cretinism 
or myxoedema at the period at which the post-mortems have been made. 
It is next in place to consider what other symptom-complexes, 
besides myxoedema, are associated with disease of the thyroid, and in 
what that association probably consists. 
The diseases to be considered are exophthalmic goitre, acromegalia 
and certain forms of obesity. 
1. The reasons for ranking Graves's disease among the thyroid 
cachexias were clearly set forth and ably championed by Moebius in 
1891, and since then various writers have taken sides in the dis- 
cussion (y. the abstracts by Moebius himself in Schmidt's Jahrb. for 
the past two years). Especially valuable are the monographs of 
Wolfler, of Gratz, and the able paper of Wette, who has had a large 
experience with thyroid diseases in all their aspects, as assistant in 
the surgical clinic at Jena. 
It must certainly strike anyone who studies the matter, that there 
is a certain likeness between the acute nervous symptoms of the first 
stage of the cachexia following either' complete or partial thyroid- 
ectomy, and the nervous symptoms of Graves's disease; and, on the 
other hand, a certain contrast between the latter and some of the 
symptoms of chronic myxoedema. This argument from the com- 
parison of symptoms does not, however, fully stand close criticism. 
There is no real contrast, for example, between the sweating of 
Graves's disease and the dry skin of myxoedema, if the former is due, 
as is probable, to central excitation of the sweat nerves, and the latter 
to disease of the cutis. 
It may be true that there is an analogy between the nervous 
erythism of the first stage of the cachexia thyreopriva and Graves's 
disease; but if this be so the cause is not evident. For in the one case 
we have to do with symptoms associated with absence of the thyroid, 
while in the other we have to do with symptoms associated with the 
presence of an enlarged thyroid, and actually curable, sometimes, by 
thyroidectomy. It is possible that irritation of the vagus and sym- 
pathetic is a factor common to both cases. 
But there are other arguments of greater weight in support of the 
thyroidal theory of Graves's disease. 
In the first place, myxoedema sometimes clo-ely follows Graves's 16 
PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
disease, or even, perhaps, accompanies it (Sollier; Von Jaksch, 
cited by Gauthier; Clin. Soc. Reports; my own second case), or the 
two diseases may occur in different members of the same family 
(Hadden, Virchow). Above all, thyroidectomy, or other operations 
on the thyroid, have proved of late years unexpectedly successful in 
the treatment of Graves's disease. Thus, Lemke has collected thirty- 
seven cases treated in this way, in all but three or four of which 
improvement or cure resulted. To this number I can add one case, 
which is, I think, the first to be reported in this country. 
The operation was done by Dr. J. C. Warren, at the Massachu- 
setts General Hospital, three months ago. The patient seems to be 
steadily, though slowly, improving. The whole gland seemed to 
have been converted into a firm mass of adenomatous structure, with 
high cubical epithelium, and, so far as examined, without colloid. 
(Councilman.) 
The probability of a connection of some sort between Graves's 
disease and myxoedema is made stronger by including the case of 
acromegalia, which bears a certain likeness to both of the others, 
presenting the rapid pulse, the tremor, and the sweating of the skin 
characteristic of Graves's disease; together with trophic changes in 
the bones and integuments of the head and limbs analogous, perhaps, 
to those of myxoedema. 
On the other hand, the experimental evidence with regard to the 
cause of Graves's disease, unsatisfactory as it is, favors rather strongly 
the view that it is due to the in jury of certain nervous arrangements ; 
and no theory should pass muster that does not attempt to account 
for the extraordinary manner in which practically the whole Graves's 
disease complex springs almost instantaneously into existence in per- 
sons with healthy thyroids under the influence of intense emotion. 
Sometimes, if the emotion quickly subsides, the symptoms may soon 
pass away (Gowers. My colleague Dr. F. Coggeshall has seen an 
exactly parallel case. The patient was a young girl, and the symp- 
toms followed immediately on great excitement attending a whipping, 
but subsided in a few days.) 
My own opinion as regards this complicated matter is that some such 
statement and explanation as that given by Wette is correct, but may 
be extended and modified. He thinks that goitre is one of the most 
important causes of Graves's disease, but not by any means the only 
cause; that the goitre may excite the cardiac and ocular symptoms, 
either by direct irritation of fibres of the cervical sympathetic or by 
indirect irritation of the sympathetic centres ; and that many of the PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
17 
general nervous symptoms are due to the action of toxic substances 
formed by disordered metabolism within the diseased gland. 
The explanation which would be most satisfactory is one which 
would include this, and at the same time cover the cases where 
Graves's disease comes on without antecedent thyroid disease, and I 
think that such an explanation can be hinted at if we do not take 
our physiology too narrowly. 
The most probable hypothesis, though it can only be stated with 
infinite crudeness, seems to me to be as follows : 
The Graves's disease complex, in common, probably, with most 
other neuroses, is the distorted correlative, or caricature, of one 
or several physiological arrangements (comp. London Lancet) in 
which the nervous system plays the central part. The thyroid has 
an abundant and mobile circulation, and is supplied with nerves from 
the vagus and sympathetic. It is thus in position to inhibit (as occa- 
sionally seems to occur : see Wette) or to accelerate the heart, and 
on the other hand it is liable to swell almost like an erectile organ 
when the heart is acting strongly and its own vasomotor apparatus is 
weakened. When enlarged, the thyroid, the sympathetic, and the 
other nerves in its neighborhood thus again act as a centre of 
disturbance. These results almost certainly occur in many cases 
of thyroid disease (comp. Wblfler, Wette, and an able paper by 
Schranz, which I regret my lack of space to cite at length). It is 
even conceivable that one of the functions of the thyroid in health is 
to act as a regulatory apparatus for the heart, and it is further con- 
ceivable that there is a quasi-physiological connection of the following 
sort between the tremor and exophthalmus of Graves's disease, the 
disordered action of the heart, and the disease of the thyroid : 
When a person is suddenly called upon for close attention, he fixes 
his eyes and holds his breath, his muscles stiffen, and his heart beats 
faster. If the attention changes to rage or fear the eyes open wider, 
the heart palpitates, the voice changes, the hand trembles, the face 
and neck may become turgid from vasomotor paralysis, and even the 
circulation and secretion of the bowels may become affected. 
As calm is restored these symptoms may pass gradually away, but 
the heart is slow to recover its tone. Judging from the fact that 
Graves' disease may immediately supervene on such events as this, 
we may assume as possible that the heart sometimes never recovers its 
tone, and that the delicate vascular apparatus of the erectile thyroid 
(which Schranz makes largely responsible for the origin of goitre) is 
also liable to suffer permanently. 18 
PUTNAM: FEEDING THYROIDS IN MYXQJDEMA. 
Eventually, nutritive changes may occur (deposition of fats in 
orbits, etc.); and a morbid complex of symptoms, interdependent 
and correlated with each other, is formed, and becomes crystallized 
into what we call a disease. 
When any member of this complex is induced, the others are likely, 
by association, to follow, and a tendency to the complex as a whole 
may possibly be inherited like a tendency to any other disease, or to 
a monstrosity. The exciting cause may be any one of many. 
Tachycardia without exophthalmus or tremor occurs so frequently 
with ordinary goitre that it hardly deserves to be called abortive 
Graves's disease, but it may at least be an analogous affection. 
The operation of thyroidectomy in Graves's disease-which, by the 
way, may be successful when it consists only in the removal of a 
sarcoma (Tillaux) or a cyst (cited by Gauthier)-may be supposed 
to act by breaking in upon the vicious circle of influences through 
which the disease is maintained. The extirpation of a part of the 
growth usually causes the rest to shrink (Wolff), just as iodine or 
external cauterization, or electrolysis, or division of the isthmus of the 
thyroid may cause the same result, and it is probably this and not the 
reduction of the thryoid secretion by removal of part of its secreting 
tissue that makes the operation of value. A new set, as it were, is 
given to the action of the nervous centres, such as more favorable 
mental surroundings may give, and in favorable cases the old equilib- 
rium is restored. It must not be forgotten that it is just as possible 
to produce this result from one side as from the other. Absolute 
repose for the nervous system, if it can be secured, as it sometimes 
can, is occasionally as effectual in causing the disappearance of the 
goitre as the thyroidectomy is in quieting the nervous excitement and 
the heart. 
It is not probable that Graves's disease is related to the functions 
of the thyroid as a trophic organ, or, at any rate, that it is due to 
either an increase or a diminution of the normal secretions of the 
gland. That it is not due to an increase of the normal secretion is 
demonstrated both by anatomical considerations (coexistence with a 
small or practically small gland) and by the fact that the myxoedema, 
which is not compatible with an increased secretion of the thyroid, 
sometimes follows closely on the heels of Graves's disease, or even 
accompanies it. Neither can we refer it to a diminution of normal 
secretion, or we should meet it more often in connection with the invo- 
lution of the thyroid. Moreover, it has often happened that all the 
symptoms of Graves's disease have come on with extreme suddenness, PUTNAM: FEEDING THYROIDS IM MYXGJDEMA, 
19 
in consequence of strong emotion, in persons with normal thyroids, 
and have again disappeared almost as quickly. Again, it apparently 
is not cured by preparations of thyroid extract. 
It is possible that disordered metabolism, due to a vitiated thyroid 
secretion, helps to keep up the nervous symptoms of Graves's dis- 
ease, but this theory is in need of more evidence than it has yet 
adduced. 
Acromegalia probably stands as near to myxoedema and diseases 
of the thyroid or kindred organs as Graves's disease, if, indeed, the 
bond be not closer. 
It is more distinctly a sort of dystrophy than Graves's disease is, 
and affects much the same parts that are involved in myxoedema, 
namely, the bones and integuments of the face and extremities, and 
eventually, perhaps, ot the whole body; for, as Klebs points out, the 
reason that the ends of the long bones show the growth the most is 
that the resistance there is least. 
The growth of the hair and nails is apt to be impaired in acro- 
megalia, though not to the same extent as in myxoedema, but, on the 
other hand, the skin often perspires freely, as in Graves's disease. 
Tremor is also common, and attacks of well-marked palpitation are 
of frequent occurrence. 
In the case of a middle-aged woman, recently under observation 
in the wards and now in the out-patient department of the Massa- 
chusetts General Hospital, I found the pulse one morning 180, 
though from her phlegmatic appearance I should not for an instant 
have expected this. She had, to be sure, taken a dose of thyroid 
powder two hours previously, but on another occasion when she had 
not done this I found the pulse 120, and during her stay in the 
hospital, under the care of Dr. F. C. Shattuck, it ranged from 90 to 
100, though she was kept perfectly still. 
Klebs, who has studied the pathological anatomy of acromegalia 
quite extensively, explains the rapid pulse on mechanical grounds, 
believing that the disease originates in an affection of the thymus 
and that vascular changes occur by which the labor of the heart is 
increased. It would not be fair for one who is no pathologist to 
offer a criticism of this theory in detail, but with the tachycardia of 
Graves's disease before our eyes it would seem more reasonable to seek a 
physiological than a mechanical explanation, as in the case of Graves's 
disease. I do not, however, mean to deny the importance of the 
thymus, or to maintain that acromegalia is distinctly of thyroid 
origin like myxoedema. I cannot dwell, for want of space, on the 20 
PUTNAM: FEEDING THYROIDS IN MYXffiDEMA. 
recent views of Marie and Marinesco, or on those presented in the 
monograph of Duchesnean, published in 1892. 
The black portion represents the number of cases in which lesion was found; the 
shaded portion the number of cases in which the organ is stated to have been normal. 
In the other cases no statement was made as to the organs. The line at the top gives 
the number of cases. The percentages are given in round numbers. 
Duchesneau calls attention especially to the occasional occurrence 
of muscular atrophy, but the theory by which he accounts for it, 
namely, pressure of hyperplastic connective tissue on the nerve roots, 
is not, I think, the true one. This atrophy is present in a typical 
form in the case recently at the Massachusetts General Hospital, 
though without other signs of nerve-root pressure, but so, also, is it 
present in a case of Graves's disease which I have had the opportunity 
of studying closely for many years, and in several other reported 
cases of that kind. The explanation given by Duchesneau would 
certainly not apply here, and, on the other hand, the occurrence of 
the atrophy in both these diseases forms another bond of union 
between them, though its nature is still so obscure. 
I have said nothing as yet of disease of the hypophysis in acro- 
megalia, and to save time I present the evidence on that point in the 
form of a table and diagram. PUTNAM: FEEDING THYROIDS IN MYXOEDEMA. 
21 
It is not certain that the dystrophic affections due to thyroid 
diseases are fully covered by myxoedema and the others that have 
been mentioned ; and in this connection three communications, two 
by Dr. F. X. Dercum and one by Dr. F. P. Henry, in 1888, 1890, 
and 1892, are especially important. They describe three interesting 
cases, characterized by great and widespread hyperplasia of the sub- 
cutaneous fat, especially accentuated at certain parts of the body, and 
attended by pain and muscle-degeneration indicating the presence of 
neuritis. Perspiration was diminished or absent, and in this and 
other respects the cases suggested myxoedema. That which makes 
them especially interesting, however, is that the thyroids of two of 
the patients, who died while under observation, were indurated and 
infiltrated with calcareous deposit. 
The name first suggested for this disease by Dr. Dercum was "A 
Subcutaneous Connective-tissue Dystrophy of the Arms and Back, 
Associated with Symptoms resembling Myxoedema." Dr. Frederick 
P. Henry first described the second of the three cases, and proposed 
the name " Myxoedematous Dystrophy." Dr. Dercum, in his final 
communication, says : 
" All of these cases lack the peculiar physiognomy, the spade-like hands, 
the infiltrated skin, the peculiar slowing of speech, and the host of other 
symptoms found in true myxoedema. 
"It would seem, then, that we have here to deal with a connective-tissue 
dystrophy, a fatty metamorphosis of various stages of completeness, occurring 
in separate regions, or, at best, unevenly distributed, and associated with 
symptoms suggestive of an irregular and fugitive irritation of nerve-trunks, 
possibly a neuritis. That this, however, does not embrace the whole truth 
is evidenced by such symptoms as the diminished sweating, the headache, 
and the contraction of the visual fields noted in Case I. 
"Inasmuch as the swelling and the pain are the two most prominent 
features of the disease, I propose for it the name ' Adiposis Dolorosa.' " 
Dr. Dercum further makes the good suggestion that the condition 
of the thyroid gland should be examined in all cases of obesity. 
The thyroid is rarely examined as a matter of routine, and least of 
all microscopically, unless attention is especially called to it, so that 
our knowledge of the frequency with which this or that change is 
present, or as to the amount of variation in structure which is com- 
patible with health, is still but slender. 
A year ago Dr. F. C. Shattuck was good enough to ask me to see 
with him a very interesting case which deserves a place in some 
such category as this, if not indeed a case of myxoedema, though, I 
believe, the improvement under thyroid treatment has not been very 
marked, except as regards the condition of the skin. The patient 
was a lady of about twenty, and the signs and symptoms consisted 22 
PUTNAM: FEEDING THYROIDS IN MYXffiDEMA. 
mainly in an increase in the subcutaneous fat, with changes in the 
skin not quite suggestive of obesity and somewhat suggestive of 
myxoedema, a change in the nutrition of the palms and soles, and a 
marked and peculiar discoloration and brittleness of the nails, asso- 
ciated with an irritability and excitability which finally developed 
into insanity. I trust that Dr. Shattuck will report the ease at 
greater length. 
List of Authors referred to in the Text. 
Affleck, Lancet, 1893, i. 419. 
Awtokratow, St. Petersburg, med. Wocbenschr., 1888, p. 105. 
Baumler, Internat. Congress, Berlin, 1890, ii. p. 137. 
Beresowsky, Beitr. z. path. Anat. u. allgem. Path., Zeigler, 1892, vol. xii. 1. 
Biondi, Berlin, klin. Wochenschr., 1889, p. 464. 
Bircher, Samml. klin. Vortriige, 1890, No. 357. 
Bourneville (etBricon), Arch, de Neurol., 1890, xix. p. 217. 
Bramwell, Lancet, 1893, ii. p. 25. 
Capobianco, La Riforma Medica, September, 1892; Arch. Ital. d. Biol., 1893, tome xviii. 
Carnwick, Lancet, 1893, i. p. 580. 
Chopinet, Comp.-rend. Soc. de Biol, de Paris, 1892, vol. iv. pp. 602-7. 
Christiani, Arch, de Phys. norm, et path., 1893, i. 
Dercum, Amer. Journ. Med. Sciences, November, 1892. 
Drobnik, Arch. f. Anat. u. Physiol., 1887. 
Duchesneau, Monograph. Paris, 1892. 
Fano, Archivio Med., vol. xiii. p. 365. 
Fenwick, Lancet, 1892, ii. p. 941. 
Fuhr, Arch. f. exper. Path., 1886, p. 407. 
Gauthier, Lyon Med., 1888 ; see also Schmidt's Jahrb., 1893. 
Gibson, British Med. Journ., 1893, i. pp. 14 and 58. 
Gley, Bull. Med., May 20, 1891; Arch, de Phys., 1892-93. 
Hadden, Clin. Soc. of London, 1885. 
Hanau, British Med. Journ., October 4,1890, p. 786. 
Henry (F. P.~), Journ. Nervous and Mental Dis., March, 1891. 
Hofmeister, Fortschr. d. Med., 1892, p. 81 et seq. 
Holman, British Med. Journ., 1893, i. p. 114. 
Horsley, British Med. Journ., 1885; 1890, ii. 201; 1892, i. 431, Internat. Beitriige, i. 396. 
Virchow's Denkschrift, 1890. 
Howitz, Lancet, 1892, ii. p. 1213. 
Hun and Prudden, Amer. Journ. Med. Sciences, 1888, xcvi. pp. 1 and 140. 
Jaksch, Von, Prager Med. Wochenschr., 1892, xvii. p. 49; Schmidt's Jahrb., 1893, p. 22. 
Jones (W. Makeig), British Med. Journ., 1888, i. p. 252. 
Jurgens, St. Petersburg, med. Wochenschr., 1889, vi. pp. 447 and 449. 
Klebs, Allgem. Path., 1889, ii. 
Kahler, Berlin, klin Wochenschr., 1892, Nos. 24, 29, and 30. 
Kopp, (J.), Virchow's Arch., 1892,128, p. 290. 
Laache, Deutsche med. Wochenschr., 1893. 
Langhans, Virchow s Arch., 1892,128, pp. 318 and 387. 
Lemke, Deutsche med. Wochenschr., 1892, No. 11. 
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23 
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1892, iii. p. 303. 24 
PUTNAM: FEEDING THYROIDS IN MYXCEDEMA. 
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