Andersson and Bergman6 have given large quantities of thyroid extract to a man who was kept in perfect quiet, and no increased output of carbonic acid was noticed. They attribute the increased metabolism which is usually observed to the increased muscle tonus caused by the highly irritated central nervous system. A high metabolism is observed in cases of exophthalmic goiter. Freidrich Miiller1 reports a case of an individual weighing only 29 kilograms who constantly lost weight notwithstanding a daily diet containing 68 grams of protein with 58 calories per kilogram. Under such circumstances there is undoubtedly an abnormally high destruction of both protein and fat. The increased protein destruction has been attributed to toxic influence of the thyroid secretion. Magnus-Levy2 finds an increased oxygen intake in cases of exophthalmic goiter amounting to 22, 42, and 70 per cent. above the normal.

1 Magnus-Levy: "Berliner klinische Wochenschrift," 1895, xxxii, 650.

2 Voit, F.: "Zeitschrift fur Biologie," 1897, xxxv, 116.

3 Rheinboldt: "Zeitschrift fur klin. Med.," 1906, lviii, 425.

4 Lusk: "Proceedings of the International Congress of Medicine," 1913, Sec. II, Pt. 2, p. 13.

5 Mansfeld: "Pfluger's Archiv," 1915, clxi, 502.

6 Andersson and Bergman: "Skan. Archiv fur Physiologie," 1898, viii, 326.

Steyrer3 made interesting experiments on the metabolism in this disease. The patient was twenty-one years old, temperature normal; the total metabolism during two days was determined twice at intervals one month apart and while the person was resting in bed. During the second period the disease had made considerable progress, the patient having a hot skin and being in a highly nervous state.

Calorimetric studies upon 12 thyroid cases have been made by Du Bois4 and the literature has been very fully considered by him. The accompanying table epitomizes the results obtained by Du Bois with 3 cases of exophthalmic goiter and with 1 cretin thirty-six years of age.

1 Muller: "Deutsches Archiv fur klin. Medizin," 1893, li, 361. 2 Magnus-Levy: von Noorden's "Handbuch der Pathologie des Stoff-wechsels," 1907, II, p. 325.

3 Steyrer: "Zeitschnft f. exp. Path, und Therapie," 1907, iv, 720. 4 Du Bois: "Archives of Internal Medicine," 1916, xvii, 915.

The Metabolism Of 3 Patients With Exophthalmic Goiter And Of 1 Cretin

The total difference between direct and indirect calorimetry in the 12 cases was 2.9 per cent.

The specific dynamic action of protein and glucose was within the normal limits, and glucose was oxidized in an entirely normal fashion, even in the presence of some glycosuria. In one experiment (Case I) 89 per cent, of his energy production was derived from glucose.

Forschbach and Severin,1 in Minkowski's clinic, state that the administration of 100 grams of glucose in exophthalmic goiter does not invariably produce glycosuria. The glycosuria is probably to be explained by a difficulty of glycogen retention in hyperthyroidism. When thyroid extracts are given to rabbits or to dogs the liver contains much less glycogen than normally.2

1 Forschbach and Severin: "Archiv fur exp. Path, und Pharm.," 1914, lxxv, 168.

2 Parhon: "Journal de Physiologie et de Pathologie gen6rale," 1913, xv, 75; Cramer and Krause: "Proceedings of the Royal Society," 1913, Series B, lxxxvi, 550.

This inability to store the normal amount of glycogen is the probable explanation of the fact that the respiratory quotients found during the determinations of the basal metabolisms of patients with hyperthyroidism invariably show a lower average level than the normal.

Du Bois finds that the height of the metabolism gives the best index of the severity of the disease and classifies very severe cases as showing an increase of 75 per cent, above the normal heat production, severe cases as showing over 50 per cent., and moderately severe and mild cases as showing less than 50 per cent, increase above the normal basal metabolism. Rest of a week in bed usually caused a 10 per cent, fall in metabolism. Thyroid sera, ergotin, and quinin hydrobromate had little effect. Ligation of the thyroid arteries was followed by a rise in metabolism in most cases. There was no indication that any conservative form of treatment was more effective than mental and physical rest.

In myxedema the metabolism is reduced and there is a fall in body temperature. Anderson1 reports a case of a woman whose metabolism was as low as 1260 calories or 18.8 per kilogram: after treatment for nine months with thyroid extracts the heat production rose to 2099 calories, or 32.3 per kilogram. These latter are normal values. The temperature rose to normal with the increase in metabolism.

The cretin investigated by Du Bois (see table on p. 442) had a basal metabolism which was 20 per cent, less than the normal adult. Response to the specific dynamic action of food was normal. The individual, by Binet's tests, had the mentality of a child of seven years, though his age was thirty-six. This condition is a rare example in which the metabolic processes are permanently depressed.

With the possession of such a gland as the thyroid, whose suppression may dimmish metabolism 20 per cent, and whose stimulation may increase it 100 per cent., it is truly strange that a normal person should have a basal metabolism so regulated as to correspond to a definite heat loss per square meter of body surface. It is no wonder that the law of surface area should be assailed as incredible and irrational. The real wonder is that the law is true.

1 Anderson: "Hygeia," Stockholm, 1898 (quoted in Tigerstedt's "Lehrbuch der Physiologie").

Of late years there has been a sharp differentiation between the functions of the thyroid and those of the parathyroid glands. Clonic convulsions are a symptom following parathyroidectomy, and during these periods the temperature rises. MacCallum1 reports that the temperature of a dog, in which after parathyroidectomy violent tetany developed, rose from 390 to 43.20 during the attack. The administration of calcium acetate stopped the convulsions in a few minutes and within half an hour the temperature fell to 38.90.

Wilson, Stearns, and Thurlow2 report that after parathyroidectomy a condition of alkalosis develops in the blood which is neutralized by the production of acids incident to tetany, or the tetany may be prevented by intravenous injection of M/7 hydrochloric acid. The action of calcium salts is to lower the dissociation constant of hemoglobin and the alveolar tension of carbon dioxid, effects which are also brought about by acids. Underhill3 states that neither thyroidectomy nor the simultaneous removal of two parathyroids out of four will alter the utilization of glucose by dogs. Only after the removal of three parathyroids is the assimilation limit for glucose reduced.

1 MacCallum: "Fever," Harvey Society Lecture, "Archives of Internal Medicine," 1908, ii, 572.

2 Wilson, Stearns, and Thurlow: "Journal of Biological Chemistry," 1915, xxiii, 89.

3 Underhill and Hilditch: "American Journal of Physiology," 1909-10, xxv, 66; Underhill and Blatherwick: "Journal of Biological Chemistry," 1914, xviii, 87.