FURTHER STUDIES ON THE GOITROGENIC ACTION OF THYROXINE ADMINISTERED WITH PROPYLTHIOURACIL, METHIMAZOLE OR PERCHLORATE

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Abstract
Several indices of thyroid and hypophysial function were measured in order to study the potentiating effect of small doses of thyroxine on thyroid growth induced by propylthiouracil, methimazole or perchlorate. Rats were fed chow (1.6 [mu]g/g iodine) or Ken-L-Kibble (0.25 [mu]g/g iodine) for a year or longer. Propylthiouracil (0.02%), methimazole (0.01%) or perchlorate (1.25%) were added to both diets. One series of rats on chow and one on Ken-L-Kibble, with and without the goitrogens, received thyroxine (25 [mu]g/100 g) in the diet, while another series did not. Although large goiters were produced by the 3 drugs, with or without thyroxine, increased sizes of goiters due to thyroxine were seen only in rats fed chow with propylthiouracil, and in rats fed Ken-L-Kibble with perchlorate. Wide variations in body and organ weights, food intake, metabolic rate PBI (protein bound iodine), thyroid and pituitary histology and, in the Ken-L-Kibble group, in pituitary and serum thyrotropin levels, were observed. It was concluded that the 3 goitrogenic drugs, administered in apparently equivalent dosage, in reality have widely differing effects and that their chromic effects cannot easily be compared, although all of them favour the formation of numerous small adenomata. However, it was concluded that the goitrogenic action of thyroxine is not limited to an interaction peculiar to proplythiouracil and seems to be mediated via an effect on adenohypophysis or higher centers.