on him by a physician. Although he was exposed to the eruptive diseases, he never suffered from any of them; he was always pale, but often his cheeks were red. He was always mentally dull, and disinclined to move about; he observed very little that was going on around him, and was incapable of learning. He has a certain amount of hesitancy in speech. His face has always been large and slightly swollen; hair somewhat dry and coarse, but skin not rough and dry as in the other children; his tongue is not large; there are no thickenings about his neck and supraclavicular regions. He is weak on his legs, walks and stands imperfectly; the muscles of his legs and arms are poorly developed; his body is large, and abdomen of considerable size; genital apparatus not fully developed. This is not as decided a case of myxedema as the two girls'. He was placed upon the desiccated thyroid, five grains twice a week, which he has continued ever since; he has presented no unpleasant symptoms at any time during its administration, except that somewhat early in its use he complained of severe pain in his legs, but nowhere else, and during this time, his mother thought, he did not walk as well as he had formerly done. I persuaded her to continue the use of the thyroid; the result has been that the pains ceased and he began to improve slowly in every respect, even in his walking; more latterly the improvement in his mental condition is more marked; he takes a lively interest in things about him; asks questions, and is quite cheerful and bright compared to his former state. There has been no reduction in the dose of the medicine at any time. CASE IV.--Sarah B., aged seventeen was brought to the clinic for nervous diseases at the Brooklyn Eye and Ear Hospital about one year ago. She had apparently been well and mentally bright for one in her station of life until she was five years, when she had scarlet fever; during convalescence "she was swelled all over her body." She may possibly have had acute nephritis. Subsequently this swelling disappeared, except in her face; she was less bright mentally after this attack; she went to school, but did not learn easily; she gradually became more dull until about one and a half years before she was brought to the clinic; the mental dulness has so much increased that she was positively stupid and apathetic; she was unable to remember what was told her; if she were sent to the store to buy a few things, she forgot what they were before she reached the store. The edematous condition of her face, especially about the eyelids, appeared to make the diagnosis of myxedema clear. She had none of the other symptoms such as en larged tongue, coarse hair, rough skin, etc.; she was given five grains of the desiccated thyroid each day; under this treatment, in a few weeks, there was a decided improvement in her mental activity, which was very apparent and gratifying to her mother. After six months of treatment her mother reported that she was bright and cheerful, the apathetic condition had entirely disappeared; she could go to a store and buy from ten to twenty articles without forgetting one of them; she is an energetic and active helper in the housework which formerly she was too stupid to attend to. You will see that she still shows evidence of the pseudo-edema, especially about the eyelids (patient shown). Unlike the other children she is fully grown; the general conformation of her head and face is not that of a high order of intelligence. She has a young brother who is now a patient at the clinic suffering with chorea. There has been no reduction in the dose of the medicine at any time. There are, as is shown by these four cases, a great many degrees of myxedema, especially in the infantile variety, but also in the adult; the clinical picture is not always complete. One The changes observed during life, and found in the post-mortem examinations, are all indications of trophic disorders. of the constant changes is disease or absence of the thyroid gland, which Hilton Fagg, in 1871, had suggested might be found to be constant. The treatment of this disease is a triumph for medical science and experimental medicine. Dr. Ord has recently remarked that two years ago, myxedema was looked upon as incurable. Many interesting studies have been made in recent years, which indicate a certain apparent relationship between myxedema and other conditions, also having trophic and nervous lesions; such as Graves' disease, exophthalmic goiter, acromegaly, and still more recently, conditions which appear closely allied to acromegaly, such as megalo-cephalie (Starr), and hyperostosis cranii (Putnam). In regard to the relationship of Graves' disease and myxedema, it is believed that the thyroid is the seat of the disease in both, because the thyroid is often enlarged in Graves' disease; in myxedema the gland is either absent or diseased, so that it does not throw into the circulation a substance which is necessary to health; in Graves' disease, that it throws too much of this substance into the lymphatic circulation. There are, however, four theories of the causation of the symptoms in Graves' disease. 1. That the heart-disorder is the primary one and affected through the sympathetic. 2. That the primary lesion is bulbar and central. 3. That the thyroid gland causes the disease by secreting toxic substances. 4. That the disease is only a concurrence of symptoms. Brissaud, who has recently discussed this question, of the connection between the symptoms in Graves' disease and the thyroid, very truly says, "The only constant symptom is tachycardia, for the goiter and exophthalmus may be absent, while the coexistence of Graves' disease and simple goiter, in the same locality, is only a coincidence. The amount of hypertrophy of the gland is variable and not proportionate to the severity of the symptoms, and it is quite contrary from facts to conclude from the anatomical changes that excessive thyroid activity is the cause of the disease; for he found that in twenty-five adult thyroids, when no symptoms of Graves' disease were present during life, not one was healthy. My own opinion has always been, and still is, that it is primarily of central origin. Brissaud also states that exophthalmus, swelling of the thyroid, and tachycardia can be produced simultaneously by cutting the restiform bodies in rabbits. The reason that acromegaly is supposed to have some relation to myxedema is the presence in acromegaly of diseased or hypertrophied thyroid with enlargement of the pituitary body; but clinically they are not at all alike, except for the presence of trophic disorders in both. The increase in the size of the body in adult myxedema, and relatively so in the child, is due to edema or pseudo-edema. In acromegaly it is due to increase in the size of the bones-the same for cephalo-megalie and hyperostosis cranii. The hair of the scalp and eyebrows is thin in myxedema, and that on the body lost; the skin dry and rough. It is the reverse in acromegaly. Much attention is being given to these conditions, for undoubtedly there is some, remote though it be, relationship between these various states. Some interesting studies have recently been made of the urine in myxedema. Drs. Ord and Edmund White made examinations of the urine of a patient, whom they treated for myxedema with a glycerin-extract of the thyroid gland. The patient was put on a restricted and selected. diet. Increase in the volume of the urine was first noticed. Up to the time of the administration of the gland the amount of nitrogen excreted corresponded fairly to the nitrogen taken in the food, and as to be expected, slightly less. The day after the first administration of the thyroid extract the excretion of nitrogen exceeded the amount introduced in the food, and this proportion was maintained as long as the patient was under observation. The records show that the relation of total nitrogen to nitrogen as urea remained about the same as in normal urine. Their conclusions from the observations are: 1. That the urea is increased in volume. 2. That the nitrogen excreted exceeds the total quantity of nitrogen in the food. 3. The phosphoric acid and chlorin elimination are practically unaffected. 4. That the increased nitrogenous excretion is chiefly in the form of urea. 5. That the body-weight is rapidly diminished. 6. That the temperature of the body is raised. More recently Denning has examined into the same subject; he gave the gland to three obese persons; he found slight increase in urea; the volume of urine was increased in one of them, and not changed in the other two. Quite naturally studies and experiments have been undertaken to determine the active agent or agents in the thyroid gland. Notkin (referred to by Bussaud, 1895) claims to have isolated from the thyroid body, a substance which he calls thyroproteid, which when injected causes myxedema and its acute complications. The actual secretion of the gland is a ferment, which converts the thyroproteid, which is collected and stored up in the gland, into a useful substance, thyroidin. If Graves' disease were caused by over-activity of the gland, there would be on this hypothesis no more thyroproteid left and the organims would be saturated with thyroidin. Renaud in 1888 has described a lesion, which is never wanting in Graves' disease, whether the gland is hypertrophied or not. This is an intralobular cirrhosis, obliterating the lymphatics, except quite at the margin of and between the lobules, by which the thyroid secretion passes directly into the veins, instead of partly into the lymphatics. I will pursue these observations and theories a little longer as they are exceedingly interesting. This, with the presence of a peculiar type of fever, led Renaud to suppose that the disease was caused by a morbid poison, which nominally underwent destruction in the lymphatics. The latter view is supported by the fact that an extract of an adult gland is harmless when digested, being absorbed in the chyle, and passing through the lymphatics. In the fetal thyroid the follicles secrete a mucous substance thyromucinin the adult a colloid-thyrocolloidin; this latter is normally pro duced in all the follicles which are connected with the lymphatics, but in exophthalmic goiter it is only found in the margin of the lobule, the central follicles being poor in thyrocolloidin, or if freshly formed, filled entirely with thyromucin. This closure of the lymphatics, which in the thyroid takes the place of an excretory duct, causes a hypertrophic cirrhosis with new gland-formation of a fetal type. Renaud believes that the normal function at the periphery of the lobules being maintained is sufficient to prevent myxedema, by pouring thyrocolloidin into the blood; in the center, however, only thyromucin is absorbed, and this he looks. upon as the poison in Graves' disease. E. Bauman, with Roos, has found that the active principle of thyroid gland is not destroyed by boiling it with dilute sulphuric acid; when such a fluid is allowed to cool, the active principle forms part of the precipitate; the precipitate can be removed by filtering and treating with alcohol; the residue to be treated with petroleum ether, to remove fat and fatty acids; then dissolved in a one-per-cent. solution of caustic soda; when this is filtered and dilute sulphuric acid added, a precipitate is formed which, when washed and dried, is a brown, amorphous substance, which has been given the name of thyro-iodin, because it contains iodin in firm chemical combination. Bauman in 1896, in an article, says that this thyro-iodin has the same therapeutic action as the thyroid gland itself in parenchymatous goiters, in myxedema, and in obesity, and the results are more rapid. There are many other interesting points referred to by Bauman. I must refer to a more recent study, confirmatory to a certain extent of Bauman's observations. In a preliminary report on the active substance in the thyroid, by Hutchison, he refers to articles of recent date by Fraenkel, Drechsel, and Bauman. He says that the bodies isolated by Fraenkel, and by Drechsel, are very different in nature from those by Bauman and himself. After some preliminary work, he began with the administration of an isolated ingredient of the gland. The product of a mass of sheep's thyroid was first divided into proteids and proteid-free watery extract. The proteids were found to be active; they are practically only two in number, a nucleo-albumin and the colloid matter. The former was inactive, the latter active. The proteidfree watery extract was then concentrated, it would contain the bodies of Fraenkel and Drechsel. It was found, even in very large doses, to produce no effect on a patient who had reacted distinctly |