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Studies on the mechanism of goitrogenic action of diphenylthiohydantoin.

Diphenylthiohydantoin (DPTH) is a potent goitrogenic compound and produces goiters in rats. Like methimazole, DPTH depresses plasma T4 and T3 concentrations and elevates plasma T4 and T3 concentrations and elevates plasma TSH concentration. Unlike methimazole, however, DPTH does not suppress thyroidal radioiodine uptake and thyroid hormone synthesis, although the monoiodotyrosine to diiodotyrosine ration is elevated by DPTH. DPTH does not inhibit thyroidal radioiodine release or augment the degradation of thyroid hormone. DPTH depresses an increase of plasma T4 and T3 in thyroidectomized rats maintained on T4 or T3 by augmenting fecal excretion of hormones. In addition, DPTH decreases conversion of T4 to T3 in vitro. It is suggested that DPTH is a unique goitrogen which acts at two different extrahyroidal sites, viz. fecal loss of thyroid hormone and conversion of T4 to T3.