Evidence that the Goitrogen, Methimazole, Interferes with the Extrathyroidal Utilization of Exogenous Thyroxine11

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Abstract
The effects of varying dietary calcium on absorption and excretion of calcium, magnesium and phosphate by intact and parathyroidectomized rats were determined. Since varying dietary calcium in intact rats influences parathyroid activity, the role of endogenous parathyroid secretion on the metabolism of these elements was also examined. The only significant differences in calcium metabolism, between pair—fed intact and parathyroidectomized (parex) rats, were in those fed very low levels of calcium. In this instance, rats with intact parathyroids absorbed more calcium, excreted less in the urine and had higher levels of serum calcium. No significant differences in phosphate absorption or balance between intact and parex rats were found at any level of dietary calcium. Excess endogenous parathyroid secretion had no effect on phosphate absorption, but increased urinary phosphate and lowered serum phosphate. A fall in urinary phosphate of intact rats with increasing amounts of calcium intake was primarily the result of decreased phosphate absorption and not a consequence of parathyroid activity. Excess endogenous parathyroid hormone decreased urinary and absorbed magnesium but ncreased its serum level. Increasing dietary calcium raised calcium absorption and its excretion into the urine which also elevated urinary magnesium.The purpose of this investigation was to evaluate the use of rats fed a goitrogen, Methimazole, for use in bioassays for thyroxine based on kidney transamidinase activities or weight gains. Intact male weanling rats were fed a complete purified diet supplemented with Methimazole (0.1 g/100 g diet) for six weeks. Surgically thyroidectomized male weanling rats were fed a complete purified diet for six weeks. There was no significant difference in the weights of the 2 groups of animals at the end of 6 weeks. All rats were then given 15 daily injections of varying amounts of thyroxine. One—half of the thyroidectomized rats were fed the complete purified diet during the injection period; the remaining thyroidectomized rats and all the intact rats were fed the diet supplemented with Methimazole. The rats fed Methimazole (both intact and thyroidectomized) required approximately 2 times the amount of thyroxine as the thyroidectomized rats to develop equivalent transamidinase activities. The thyroidectomized rats fed Methimazole required approximately 2 times the amount of thyroxine as the thyroidectomized rats to develop equivalent weight gains. Methimazole is concluded to interfere with the biological effects of exogenous thyroxine. The extrathyroidal inhibition of thyroxine by Methimazole precludes the use of Methimazole in thyroxine assay procedures when the bioassay is based on kidney transamidinase activities. If the bioassay is based on weight gains of intact rats fed Methimazole only a slight inhibition of the biological effect of thyroxine is detected.(Endocrinology92: 160, 1973)

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