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Sixty Fischer 344 rats were fed a diet containing 90 ppm methimazole, a known antithyroid compound. Following exposure to the test compound, groups of ten animals were terminated at 1, 3, and 6 months. Similar groups of ten treated animals were given control diet for a reversibility period of 2, 3, and 6 months, respectively. Groups of ten control rats were terminated after 1, 3, 6, and 12 months. Except for the expected effect on body weight, the treated animals had no physical signs of toxicity. The weight of thyroids increased with the duration of exposure, becoming in males after 6 months about ten times the weight of thyroids from control rats. Thyroids of treated rats after 1 and 3 months had a diffuse homogeneous hypertrophy and hyperplasia of follicular cells, decreased colloid, and increased vascularity. After 6 months' exposure to the antithyroid compound, there was diffuse hyperplasia but also a heterogeneity in the size and morphology of follicles, protrusion of follicular tissue through the gland capsule and into vascular spaces, and the development of follicular nodules. Treated rats placed on control diet, allowing for reversibility, had thyroids which were decreased in size with large follicles and flattened epithelium, and a complete remodeling of most nodules with no evidence of progression. Although the nodules produced after prolonged administration of the antithyroid compound had many of the characteristics of neoplasia, the biologic behavior supports the diagnosis of nodular hyperplasia.

Induction and Reversibility of Thyroid Proliferative Changes in Rats Given an Antithyroid Compound