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2. Pituitary hypersecretion large incisors, separated. = small lateral incisors.

3. Gonad hyposecretion

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2. Thyroid hyposecretion loss of hair.

3. Suprarenal hypersecretion = hairy; eye-brows heavy and meet. 4. Suprarenal hyposecretion scanty hair; moles and pigmented spots. 5. Pituitary hypersecretion hairy.

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The following discussion of the activities and therapeutic uses of the endocrine glands represents the best consensus of opinion at this date. The text is derived from a careful study of the literature combined with the writer's own long clinical studies of the action and use of the organ extracts and a personal study of very many cases of endocrine disturbances. It should be recognized that the rapid development of new data concerning the physiology and chemistry of these glands may make parts of this discussion at any moment obsolete.

ENDOCRINE GLANDS THAT HAVE POSITIVE THERAPEUTIC VALUE

THYROID GLAND

Physiology. Although the thyroid gland weighs only about one ounce, it is estimated that, with a normal rapidity of the heart, all of the blood of the body passes through the gland about once an hour. If the blood-vessels of the thyroid are enlarged, or if the heart acts more rapidly, theoretically the blood of the body would pass through the thyroid much more frequently than once an hour, and even with a normal thyroid secretion the blood could take up more of it than is necessary for health.

There may be small supernumerary thyroids, and there may be an intrathoracic thyroid. Fetal thyroids are relatively larger

and contain relatively more iodine than adult glands. Females have more thyroid tissue and consequently normally more iodine than males. Some drugs increase the activity of this gland, notably strychnine and caffeine, hence tea and coffee are stimulant to it. Animal proteins increase its activity. Quinine in large doses and morphine diminish thyroid activity. Privation of milk and vegetables and drinking a very soft water, as rain water, may cause not only calcium deficiency but thyroid disturbance.

Normal function of the thyroid promotes the normal skeletal growth of children; diminished function inhibits such growth. Good thyroid activity causes the growth and development of perfect teeth, both as to color and spacing.

The thyroid normally enlarges and hypersecretes during pregnancy. If it does not do so, the teeth of the pregnant woman decay, her nails become brittle, and she loses some of her hair; i.e., she shows signs of too much loss of calcium, her reserve being used for the growth of her child. She then shows the need both for more iodine to properly stimulate the thyroid, and for more calcium. Insufficient thyroid secretion in the pregnant woman may cause an enlarged thyroid in the child at birth, or the child may have an insufficient thyroid.

If the thyroid does not hypertrophy in pregnancy there is a tendency to toxemia in the mother and to imperfect development of her child. If the mother has subthyroid secretion. after the child is born, she should not nurse her child, unless she is given thyroid extract, or the child is given it. Often, also her milk may not be sufficient in other qualities for the welfare of the child. It may not contain the normal amount of vitamines. A child's brain does not well develop, if the thyroid secretion is insufficient.

The thyroid seems to have a close relation to the pancreas, and its secretion is perhaps inhibitive to hyper-functioning of the pancreas, as when the thyroid subsecretes the pancreas often over-secretes and glycosuria results. On the other hand, in cretins and in myxedema the blood sugar is often decreased. There is also a tolerance for sugar, and often a great desire for it. All metabolism is slowed in subsecretion of the thyroid,

and fat is deposited, perhaps due to a disturbed carbohydrate function.

One of the most important activities of the thyroid is its ability to prevent poisoning of the body, especially the poisoning that occurs from acute or chronic infection. If the thyroid is insufficient or becomes insufficient from such poisoning or irritation, life is endangered, and the patient is benefited by the administration of iodine or thyroid extract. In thyroid insufficiency there are more or less poisonous substances circulating in the blood. The seriousness of chronic focal infection, either of the mouth or tonsils, in causing primarily enlargement of the thyroid and secondarily insufficiency of the thyroid, should be recognized. On the other hand, such an infection often causes the thyroid to hypersecrete, and Graves' disease develops, hence a focal infection as the probable cause should be sought. If the thyroid under-secretes, the danger may not be recognized, but the patient is more likely to succumb to, or to be seriously affected by, any acute disease that attacks him. With mouth infections, and the streptococcus viridans as the infecting agent, it may be for a time difficult to tell whether the irritated thyroid or the germ is the cause of the cardiac symptoms. Both causes may be active at the same time.

An enlarged thyroid is frequently an evidence that it is trying to overcome a chronic toxemia. Therefore many times the thyroid is supposed to be at fault when it really is doing its best to overcome some other condition that needs treatment. An individual who has survived many infections and serious conditions in all probability has a very normal thyroid. When the thyroid is hypersecreting it may cause serious cerebral disturbance by its ability to break down the phosphorized fats.

If there is too much thyroid secretion, or if thyroid extract is given a child when it is not needed, there will be an early development of the secondary sexual characteristics and an early maturity. If a child does not grow, such slow growth not being due to thyroid insufficiency, thyroid feeding will not increase the growth and may even retard it.

If the thymus secretion is insufficient in childhood, and thymus gland is administered, a too early maturity will be prevented; but, if the thymus is sufficient and thymus gland is fed, the general growth may be increased but secondary sexual characteristics and maturity will be postponed. Too much thyroid secretion soon after puberty in girls may cause them to be immoral.

In Graves' disease there is a diminished tolerance to carbohydrates, perhaps due to an increased secretion from the posterior lobe of the pituitary, or due to pancreatic disturbance, or to liver irritation, or perhaps due to all of these factors, hence glycosuria is frequently a symptom. Also, feeding large doses of thyroid extract may cause glycosuria.

Feeding of thyroid to married women tends to allow pregnancy to occur. This is especially true in sub-thyroid cases, even when there has long been sterility.

One of the chief functions of the thyroid is to take iodine from the blood and store it to form its active substance, thyroxin. If the thyroid cannot do its work, the pituitary may assume some of the thyroid activity. In certain forms of thyroid insufficiency and in certain forms of enlargement of the thyroid, iodine in small doses, or an iodide in small doses, may cause the gland to return to normal.

In endemic goiter there is likely to be a diminished amount of iodine in the thyroid and retention of calcium in the body. In toxic goiter, there is likely to be a large amount of iodine in the thyroid, and calcium is rapidly lost from the body.,

Feeding of iodine may change an enlarged hyperplastic thyroid to one of the colloid type. In hyperthyroidism calcium should be given both with the food (milk) and as a drug, and calcium deficiency, either from an increased loss, or from lack of it in the food, is the cause of some of the symptoms of hyperthyroidism. Starvation seems to reduce the size of the, thyroid and to decrease its normal activity. Therefore it is important when there is serious vomiting, or for any reason the patient cannot receive food, that small doses of iodine should be given in some manner, perhaps by allowing iodine to evaporate in the room.

While thyroid tissue can be planted and live for a time, it is absorbed, but until such absorption has taken place, it may ameliorate the symptoms caused by the absence of thyroid secretion. By the time the graft has absorbed, in some patients the portion of the gland left after operation, or supernumerary glands, may have become enlarged and furnish sufficient secretion.

Thyroid substance given by the mouth is not injured by digestion, and it not only causes thyroid activity, but increases the amount of urine and the nitrogen output, especially in nephritis. If there is a need for thyroid, small doses will not cause loss of weight, and may even cause a gain of weight, although large doses long continued will always cause a loss of weight.

In hyperthyroidism the blood is less coagulable, which may be due perhaps to the coincident extra loss of calcium from the body. There is much more tendency to hemorrhage in hyperthyroidism than in normal thyroid activity, and in hypothyroidism the blood generally coagulates more rapidly than in hyperthyroidism.

If the thyroid gland is removed, the hypophysis, both anterior lobe and pars intermedia, become enlarged, showing some coöperative function of these two glands; and in acromegaly, which is due to pituitary disease, the thyroid is hypertrophied.

There has been shown to be a greatly increased basal metabolism, even to 80 per cent. in Graves' disease, and a greatly diminished basal metabolism, even to 40 per cent. in myxedema. This shows the necessity for normal thyroid secretion for normal metabolism. Recent statistics of examination of men recruited for the army in this country have shown an enormous number of enlarged thyroid glands, and in a considerable number of these cases the glands were notably enlarged. While a good many of these men may have come from districts where there is endemic goiter, unfortunately it was not noted, and therefore we have not sufficient data to show, how frequently with these enlarged glands there was mouth or tonsil infection. Probably there was such infection in a large percentage of the cases.

There are various types of enlargement of the thyroid gland: