Physiological effects of thiouracil and similar drugs on sheep.

T HE discovery of thiouracil and its derivatives as potent substances for inhibiting the function of the thyroid gland (Astwood, ~943; Astwood et al., I94 ~ and McGinty and Bywater, I94g) has made it possible to study some of the effects of limiting thyroid functions. A detailed report indicative of the effects of these substances on the thyroid gland is given by Astwood et al. (~943). They reported rapid enlargement of the thyroid glands of rats during the first few weeks of treatment. Microscopic examination showed a marked hyperplasia of the follicular epithelium, a decrease in stored colloid and an increase in vascularity of the glands. The thyroid glands of rats treated for two to six months with a diet containing ~ percent sulfagaanidine or o.~ percent thiourea in the drinking water still exhibited an orderly cellular arrangement and upon cessation of treatment the glands rapidly regressed toward a normal condition. Increased blood cholesterol has been associated with thyroidectomy and hypothyroidism of the dog (Schmidt and Hughes, i938; Thompson and Long, I941; Entenman, Chaikoff and Reichert, 194:0, of infant rhesus monkeys (Fleischmann et al., 1943) and of humans (Hurxthal and Simpson, I941). Wilkins et al. (194~a, I941b) found serum cholesterol to be higher in hypothyroid than in normal children. No significant trend in serum cholesterol of adult rhesus monkeys occurred as a result of administering thiouracil (Aranow et al., 1946) Leukopenia and granulocytosis have occurred frequently as a result of administering thiouracil and thiourea to humans and similar findings have been reported with rats by Goldsmith et al. (1944) and Williams et al. (i944). Hughes (I944) found a slight but statistically significant difference in tile hemoglobin levels of thiouracil-treated and control rats. Levin and Leathem ('94~) reported an increase in the serum globulin of rats as a result of thyroidectomy and an increase was also shown by Leathern (t945a) (I945b) as a result of administering thiourea. Evidence that the thyroid plays a part in the conversion of carotene to