Inhibition of peripheral deiodination of 3,5,3′-triiodothyronine: an adverse effect of propylthiouracil in the treatment of T3-thyrotoxicosis

An inhibition of peripheral conversion of T4 to T3 is thought to be of benefit in the treatment of thyrotoxicosis. Therefore, propylthiouracil (PTU) has been considered to be more effective in the therapy of hyperthyroidism than methimazole, since the former has the additional peripheral effect of decreasing the conversion of T4 to T3. From in vitro studies PTU is known, however, to inhibit the deiodination at the 5′ as well as at the 5 position of the iodothyronine molecule. To study if PTU blocks degradation in T3 in vivo as well, the effect of PTU on thyroid hormone concentrations in serum and liver tissue during a constant and high administration of T4 or T3 to rats was followed. It was shown that PTU clearly inhibits T4 and reverse T3 degradation. Moreover, simultaneous treatment of the rats with T3 and PTU resulted in a significantly higher increase of T3 concentration in liver tissue (11.5 ng/g liver vs 5.6 ng/g liver) and serum (615 ng/dl vs 345 ng/dl) than with T3 alone. This effect may be explained by an inhibition of the T3 degradation by PTU in vivo as well. Provided the results obtained from these animal experiments can be applied to the situation in man, the inhibition of peripheral deiodination could have an adverse effect at least in the treatment of T3-thyrotoxicosis.