On the mechanism of goitre formation during lithium treatment in the rat.

Abstract

ABSTRACT In the first experiment Sprague-Dawley rats were given antithyroid drugs i. e. perchlorate (KClO4), carbimazole (CI) and potassium iodide (KI) for 4 weeks, either alone or in combination with lithium (Li) (5 mEq./l) for the last 2 weeks. In combination with CI or KI, Li aggravated the goitre and decreased the synthesis of T3 + T4, as measured by chromatography. The weights of the adenohypophyses increased and those of the adrenals decreased in all the experimental groups. In the second experiment, Li (10 mEq./l) was administered to euthyroid rats for 4, 10 or 20 weeks. The metabolic effects of Li reached a peak at 4 weeks, giving a decreased T3 + T4, a decreased plasma PBI level and an increased plasma bioassayable (McKenzie) TSH level. A definite goitre did not develop until 20 weeks. In the third experiment the disappearance of thyroidal 131I was shown to be delayed in rats treated for 2 weeks with Li or T4 but was accelerated in those rats receiving CI. It is concluded that 1) Li accentuates the antithyroid and goitrogenic potency of antithyroid drugs, 2) Li itself is a mild antithyroid and goitrogenic agent, which exerts its effect by inhibiting the coupling reaction of iodotyrosines and 3) that Li also retards the secretion of thyroid hormones from the thyroid gland.