the peculiar muscle irritabilities seen in certain nervous diseases are due to disturbances of, or injuries to, the parathyroid glands, and in certain conditions they have been found suffering from hemorrhagic disturbances.

MacCallum and his associates showed that the serious symptoms caused by parathyroidectomy were almost instantly cured by the intravenous injection of a solution of a calcium salt, five per cent. of either the acetate or lactate of calcium. When the solution was given by the mouth it was as effective, only it acted more slowly. The beneficial action lasted for twenty-four hours, when tetany would again occur, and again disappear on another injection or administration of the calcium. They found the potassium salts aggravated the symptoms of the tetany. There would seem to be no question that the parathyroids have, as one function at least, control of calcium metabolism or of calcium absorption and assimilation. When there has been great calcium loss, and nervous irritability is the consequence, as sometimes occurs with too frequent pregnancies, and with the cerebral excitement (spasmophilia) that occurs in serious illness, and that often occurs in hyperthyroidism the administration of calcium is sedative to the whole nervous system. Probably in these conditions the parathyroids have either been overworked and have become insufficient, or they are not functioning properly.

Kendall1 suggests that an important function of the parathyroids is to convert ammonium carbonate of the protein metabolism of the body into urea, and urea may be formed in various parts of the body.

Halsted2 showed that parathyroid tissue could be successfully transplanted into the thyroid gland and into the rectus muscle of the abdomen in 61 per cent. of the cases, provided there was deficiency of parathyroid in the animal, in other words, that more than one-half of the parathyroid tissue had been removed. If there was no deficiency the parathyroid transplant was not a success. Therefore it would seem wise when, in the human subject, the parathyroid glands must be, 1 Journal A. M. A., March 11, 1916, p. 811.

2 Journal of Experimental Medicine, No. 1, 1909.

or have been inadvertently, removed, that parathyroid tissue should be transplanted, especially as Halsted showed the tissue could survive and prevent tetany for months. One parathyroid gland embedded in the rectus muscle seems to be sufficient. Unfortunately more recent attempts at transplantation of these glands have caused only temporary success. Underhill has shown that these glands are concerned in carbohydrate metabolism; also they have seemed to have something to do with the calcification of bone in growing animals.

Infantile tetany would seem to be due to parathyroid disturbance, the symptoms being somewhat similar to parathyroid extirpation, and Noel Paton and his associates, of Glasgow University, conclude that idiopathic tetany and the tetany following extirpation of the parathyroid glands are similar, the symptoms being due to such chemical mistakes as cause poisoning from guanidine or its derivatives.

Howland and Marriott, of Johns Hopkins, have found a diminution of calcium in the blood serum in cases of tetany. This bears out the clinical fact that the administration of calcium inhibits or prevents tetany, although, if symptoms of tetany are present, it is advisable to give sedatives, and probably bromides are the best, until the blood has become again saturated with calcium.

As a quieter of the nervous system calcium and alkalies have long been known to be efficient, and the relation of hyperacidity, or acidosis, to irritation of the central nervous system is of course well known. Consequently, the suggestion is not surprising that irritation of the parathyroids, which glands are so closely related to calcium metabolism, might be a cause or an associated cause of epileptic convulsions. The saturation of the body with alkalies, and especially with calcium, always more or less diminishes the frequency of epileptic attacks. The convulsions of eclampsia and of uremia are probably also associated with more or less acidosis and possibly more or less disturbance of calcium metabolism. Of course profound acidosis causes stupor and coma, but alkalies are always sedative to the nervous system, and more or less combat the serious nervous symptoms of acidosis.

Quite the reverse of this condition was shown by Wilson1 and by McCann,2 that extirpation of the parathyroids causes a condition of alkalosis due to a disturbance of the relations between the acids and bases. These experimenters agree that tetany is due to a condition of alkalosis.

It is possible that while complete parathyroidectomy causes alkalosis of the system, dysfunction or hyperfunction of these glands might cause an acidosis, each condition corrected by chemical substances. If tetany is due to an alkalosis it seems rather paradoxical that calcium salts should cure it; however, perhaps no more paradoxical than that frequently hyperacidity of the stomach is cured by the administration of dilute hydrochloric acid, which seems to prevent the developement of abnormal acids. Therefore the success of calcium salts in tetany may be due to the substitution of normally related alkaline salts for abnormal alkaline salts.

Associated with the calcium function of the parathyroids is also the calcium function of the thyroid, ovaries, and testicles, and all of these glands play some part in the most interesting story of calcium.

Winternitz has suggested that there is a disturbance of the calcium metabolism in tuberculosis, and it has been recognized that the more calcium given the tuberculous patient the better; i.e., plenty of milk and the administration of calcium salts. Tuberculous lesions are cured by local deposits of calcium salts.

The amount of calcium used in the body is very small, and it has been estimated that only about 0.01 per cent. of the calcium of the body is in the soft tissues; it is practically all in the bones. There is more calcium relatively in the brains and bodies of children than in adults, consequently any diminution of the calcium makes them more likely to have tetany or convulsions. Calcium is retained by infants and children longer than by adults, and when an excess of calcium is administered, it is very slowly excreted. An increased excretion of calcium is generally associated with an increase excretion of magnesium,

1 Journ. Biolog. Chem., 21, 1915, p. 169; and Journ. Biolog. Chem., No. 23, 1915, p. 89.

'Journ. Biolog. Chem., No. 35, 1918, p. 553.

and they appear in the urine as phosphates. But L. B. Mendel has shown that the administration of hydrochloric acid increases the excretion of calcium more than that of magnesium.

The heart muscle, in certain weak conditions, is strengthened by the administration of calcium, and as above suggested, tuberculous patients need an excess of calcium. Too frequent pregnancies, or at times any pregnancy, may deplete the mother of her calcium, in order to properly nourish her fetus and for the fetus to properly grow. If she is so depleted, fatty degenerations may occur, especially of the liver, also her bones may soften.

The parathyroids have been found diseased and to have had hemorrhages into their tissues in some cases of tetany, but they have not been often found pathologic in gastric tetany. Although on account of the muscle irritability which is present in paralysis agitans the parathyroids have been thought to be in trouble in this nervous condition, this has not yet been proved, and they have been found normal in such cases. Parathyroid disturbance has been suggested as a cause of cataract, but there is no proof of this relationship. These glands have been found abnormal in the insane.

Spasmophilia in acute infections may be due to a disturbance of the parathyroids. If there has been much loss of calcium from any cause, however, such calcium privation would account for the spasmophilic condition, and certainly in all serious infections an extra amount of calcium should be given as soon as there is the least sign of cerebral irritation. It is well to give extra amounts of calcium in the last months of pregnancy, especially if the mother has loss of hair, brittle nails, and decay of the teeth.

It is possible that some of the paroxysms of whooping cough may be due to parathyroid irritation, and it has been suggested that hemorrhages into the parathyroids may be a cause of sudden convulsions and death in infants.

We may conclude that the parathyroids are closely associated with calcium metabolism; closely associated chemically with the substance guanidine that may cause muscle irritations; and, therefore, that these glands may be disturbed in all conditions

that cause nervous irritation and convulsions. It is a fact that removal of the parathyroids will cause tetany, and that tetany is probably not alone due to a loss of calcium, but to some poison circulating in the blood or to an alkalosis, due to the removal of the parathyroid glands, and therefore to the absence of parathyroid function.

Parathyroid extracts, given hypodermatically, are always of value after parathyroid extirpation, but ordinarily the administration of calcium is as efficient.

We may sum up the uses of parathyroid extracts by stating that small doses of parathyroid may be of benefit in all cases of muscle irritability. The dose should be very small, and the frequency of its repetition or the length of time it should be given depends upon the condition for which it is used. Preparations of the glands may be obtained in the form of a powder or as tablets, the dose is about 0.006 Gm. (10 grain), once or twice a day. However, it has not been shown that in such a condition as paralysis agitans this extract is of any more value than is the administration of calcium, and in such serious conditions as eclampsia better treatment is large doses of thyroid combined with large doses of calcium and sodium salts. In other words, it has not been shown that parathyroid glandular extracts should be much used in medicine.

PITUITARY GLAND

Hypophysis Cerebri

Description. The pituitary body, or hypophysis, is located at the base of the brain in the sella turcica, and consists of two lobes; the anterior larger lobe is oblong in form, and the posterior smaller lobe is round. The pituitary body varies greatly in size, having an average weight, in the adult, of perhaps half a gram, and is relatively larger in the child than in the full-grown individual. There is a communication termed the infundibulum, more or less patulous, that connects the posterior lobe with the third ventricle. The anterior lobe is distinctly glandular in structure, resembling somewhat the thyroid, while the posterior lobe is composed largely of nervous tissue and some glandular