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A new concept for the pathogenesis of thyroid disease]. The classical concept of thyroid hormone regulation is based on a hypothalamic regulation of TSH secretion, but a peripheral regulation of thyroid hormone production may be also of importance. We evaluated the peripheral effect of TSH on human thyroid cell function in vitro. Cultures were established from specimens of healthy and thyroidectomized thyroid tissue obtained from multinodular goiters. Thyrotropic and/or antithyrotropic factors in serum were determined by reverse hemolytic plaque assays. TSH stimulated the conversion of thyroxine into triiodothyronine in thyroid cell cultures of multinodular goiters, which was directly correlated with the increase in thyroxine deiodination. The stimulation was more marked in patients who had been thyroidectomized. The results of this study indicate that the peripheral effect of TSH on thyroid hormone production is independent of the control by hypothalamic TSH. 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