EVALUATION OF THE ANTITHYROID ACTIVITY OF 5-IODO-2-THIOURACIL1

Abstract

Experiments designed to test the antithyroid potency of iodo-thiouracil (ITU), reputed to be a non-goitrogenic antithyroid agent, revealed that it is relatively weak, as compared on a molar basis to propylthiouracil (PTU) or thiouracil (TU) in the rat. When administered at concns. at which its goitrogenic action is minimal it fails to suppress thyroid hormone synthesis completely as judged by (1) QO2 of liver and kidney slices; (2) presence of reduced but appreciable concns. of organic I in the thyroid gland (3) inability to degranulate totally the alpha cells of the anterior pituitary gland; (4) incomplete growth suppression and (5) only slight acceleration of the rate of release of thyroidal I131. Admn. of high levels of ITU (1% in the diet) results in marked goitrogenicity and evidence, from the above criteria, of essentially complete suppression of thyroid hormone synthesis. No evidence was found to indicate that ITU inhibits either the release of TSH or its action in stimulating the thyroid gland. In contrast to recent reports, ITU not only does not decrease the total I content of the thyroid gland but actually results in an increase. When goitrogenic levels of ITU are administered the organic I content is reduced to a level comparable to that seen with the admn. of PTU or TU. Effects similar to those observed with non-goitrogenic doses of ITU were duplicated in part, by the simultaneous admn. of low doses of TU (0.025% in the diet) and equimolar iodide ion (0.022%). P32 uptake by the rat thyroid gland was found to be a relatively insensitive criterion for estimation of TSH stimulation of the thyroid; its usefulness as an assay procedure in this species appears quite limited.