plexuses and hence to an increased amount of cerebrospinal fluid.

Very commonly pressure from the enlarged pituitary body or from tumor growth in this region on the optic commissure causes disturbances of the eye with narrowing of the visual fields.

If the degeneration of, or the growth of the pituitary progresses, various cerebral disturbances can occur, from epileptic convulsions to insanity; also cerebral symptoms from pressure may occur.

Sooner or later, with the disturbance that probably started in the anterior lobe, the posterior lobe is disturbed, and if it hypersecretes glycosuria is likely to be a symptom, and if it hyposecretes there is increased tolerance to carbohydrates, more or less polyuria, and many digestive disturbances occur.

Not every case of tumor growth in the sella turcica causes acromegalic symptoms, but in every case of acromegaly the pituitary gland is diseased.

For a detailed description of the disease of acromegaly the reader is referred to the author's article in Buck's Handbook of the Medical Sciences, Vol. 1. A description of the third case of acromegaly reported in America and the eighth in literature will be found in the author's article in the Transactions of the Association of American Physicians for 1897. An elaborate literature on the subject of pituitary diseases will be found in the book and articles published by Harvey Cushing.

The treatment of this disease which generally has a duration of many years (unless the disease is due to a rapidly growing tumor) is not very satisfactory. There is no drug that will inhibit the increased secretion of the pituitary, and if it is caused by a cystic growth, a sarcoma or other malignant tumor, it will rapidly progress to a fatal termination. If the disease is not caused by a malignant growth, and death is not caused by some intercurrent acute illness, the patient dies asthenic, with very low blood-pressure and failing heart. In the beginning of giantism and of acromegaly the operation to remove a portion of the anterior lobe would seem justifiable, especially as the splendid technique offered by Cushing has made the operation possible. Recently radiotherapy has been tried on

pituitary growths, and this may be a successful method of treating the condition. It certainly should be tried before operation is deemed advisable.

In the more or less advanced stages of acromegaly the anterior portion of the pituitary is probably not hypersecreting, but may even be subsecreting, and the posterior lobe is generally not secreting normally, as shown by low blood-pressure and an increased tolerance to sugar. In this condition the administration of whole pituitary gland extracts improves the patient, may relieve the headache, increase the blood-pressure and heart tone and the muscle strength. If severe headache and cerebral symptoms are caused by cerebral pressure decompression may be done, or more radical surgical procedures would seem advisable. As previously stated, many of the symptoms of acromegaly are due to associated disturbances of other endocrine glands, especially the thyroid and the gonads, probably frequently the parathyroids and the suprarenals, and not infrequently the thymus has enlarged and renewed its activity. As in all disturbances of the central nervous system and especially in disturbances of calcium metabolism, the administration of an extra amount of calcium in the form of milk or the lactate or glycerophosphate of calcium diminishes the nervous irritability. Hyposecretion.-When the anterior lobe secretion is deficient in young children infantilism occurs, i.e., bone growth is interfered with, and the child remains small. If this secretion is insufficient at the adolescent period the hair does not grow in the axillæ and on the pubis, the genitals remain infantile, and the child does not develop. Also there is more or less pigmentation likely to occur on the body which is probably due to coincident suprarenal disturbance. In these conditions although small doses may stimulate growth somewhat, treatment with pituitary extracts is not very satisfactory, and Goetsch has shown. that large doses of pituitary fed to animals will inhibit growth, and feeding posterior lobe extract retards the development of the sexual glands. With hyposecretion of the pituitary there is testicular atrophy, and males assume the feminine type, and after castration eunuchs grow large and fat, showing an associated disturbance of the pituitary secretion.

Hydrocephalus may accompany hypopituitarism, and associated with it there may be adiposity and sometimes genital abnormalities. So-called juvenile obesity is due to hyposecretion of the pituitary, and these children are large, fat, have protuberant abdomens, scanty development of hair, small genitals, sometimes dry skin, and frequently are not mentally bright.

Hyposecretion of the posterior portion of the pituitary in older individuals may cause an abnormal development of fat deposited on the parts that are typical of Dercum's disease, adiposis dolorosa. This condition is probably caused by an associated disturbance of the thyroid gland.

Cushing thinks that the increase in weight in subhypophyseal secretion may be due to the coincident disturbance of the testicles or ovaries, and he also thinks that the islands of Langerhans in the pancreas may be disturbed and be a cause of the glycosuria sometimes seen in these subpituitary cases.

In the cases of slightly lessened secretion of the pituitary there often are symptoms not much dissimilar to those caused by a large amount of adenoid tissue in the nasopharynx, and frequently it has been noted that when these adenoids are removed the child begins to normally grow. Hence it is suggested that the adenoids in the nasopharynx may have something to do with the disturbance of the pituitary. In old age this gland, as many other glands, seems to atrophy.

There may be a hyposecretion of one part of the pituitary and at the same time a hypersecretion of the other part of the gland; or both portions may have a disturbed secretion. There may even be acromegaly from dysfunction without enlargement of the gland. Hence the function of the pituitary cannot be determined by an x-ray picture outlining the size of the sella turcica, and a small sella turcica does not necessarily show that the pituitary is insufficient. Also it should be noted that growths or disturbances in other parts of the brain may cause dysfunction of the pituitary without any sella turcica evidence.

The typical evidences of subsecretion of the hypophysis, termed Fröhlich's syndrome (dystrophy adiposogenitalis) are deposits of fat on the hips, on the sides of the thorax, over the

pubis, scanty growth of hair everywhere except on the scalp, small genitals, in girls and women after maturity absence of menstruation, lack of sexual desire in both sexes, soft skin, lowered temperature and sometimes polyuria and thirst. There may be headache, drowsiness, loss of memory, and even more serious cerebral disturbances. Sometimes fat is deposited on the hips, thighs, and abdomen, and occasionally in women there is an increased amount of hair growth.

There is likly to be digestive disturbances, subnormal temperature, low blood-pressure, and, as Plummer has shown, a lowered basal metabolism. Sometimes these patients develop a cachexia and die asthenic, as in acromegaly.

Sometimes dysfunction of the pituitary causes hypertension, a slow pulse, and some exophthalmos, but it should be constantly borne in mind that it is very rare that the symptoms present are due to disturbance of only one of the endocrine glands, as the interrelations are so close that the disturbance of one causes dysfunction of others.

Uses. The administration of pituitary extracts for disturbances of the secretions of the gland have not been very successful. Not infrequently, however, pituitary headache is cured by the administration of extract from the whole gland. If the patient is stout and is a woman, and amenorrhea is also a symptom, the combination of thyroid and pituitary treatment is very successful, unless the headache is due to a tumor. It has been stated that posterior lobe extracts would increase the mammary secretion, but this has not stood the proof of test. When administered by the mouth, instead of increasing the bloodpressure, it may occasionally cause some depression, loss of heart strength, and if long given, emaciation. These symptoms may develop because these extracts are likely to contain large amounts of extracts of nervous tissue or histamin. Abel and Nagayama1 have found considerable histamin in commercial post-pituitary extracts.

The administration of anterior pituitary has its greatest value in dystrophy adiposogenitalis, but such treatment is more successful if combined with appropriate thyroid treatment, 1 Journ. Pharm. and Exp. Thera., Baltimore, June 1920, p. 401.

and probably it is well in females to add ovarian extracts and in males testicular extracts to the treatment.

The most important use of extract made from the posterior lobe (often termed infundibular extract) is in obstetrics. For this purpose it is always given hypodermatically in doses of 11⁄2 to I mil. The drug has been used too frequently, as it may cause asphyxia of the child or rupture of the uterus. It should never be used unless the cervix is completely dilated and there is no obstruction to the free passage of the child through the pelvis, and it may always be advisable to administer an anesthetic as the head of the child is passing over the perineum, if the contractions of the uterus have been increased by the pituitary injected. Infundibular extracts should not be used in normal labor, and perhaps never should be used in a primipara, and the dose should be small in a multipara. Under its action the uterine contractions are brisk and frequent, and unless the child is rapidly born it becomes asphyxiated from interference with the placental circulation. In post-partum hemorrhage this preparation is not as valuable as is ergot.

Pituitary extracts administered by the mouth have sometimes been given in menorrhagia or metrorrhagia, but they are not as efficient as ergot unless pituitary disturbance is a cause of the bleeding. If there is no evident cause for menorrhagia or for too frequent menstruation in young girls, mammary extract represents the best treatment, although if the girl shows signs of pituitary disturbance a combination of these two glandular extracts will be of greater value.

In conditions of cardiac failure and in shock with low bloodpressure and whenever there is dangerous low blood-pressure extracts of the posterior lobe given hypodermatically in 1 mil doses is of benefit. It acts less rapidly than epinephrine preparations, but its action is much more prolonged. It also has an advantage in these conditions of promoting activity of the kidneys.

After abdominal operations when normal intestinal peristalsis is not present and there is a tendency to tympanites pituitary extracts given hypodermatically are of great value. One mil may be injected hypodermatically every twenty-four hours