Extrathyroidal Effects of Propylthiouracil and Carbimazole on Serum T4, T3, Reverse T3 and TRH-Induced TSH-Release in Man

Abstract

A possible extrathyroidal effect of propylthiouracil (PTU) and carbimazole on serum levels of thyroxine (T4), triiodothyronine (T3), 3,3\m=' \,5\m=' \-triiodothyronine (reverse T3) and on thyrotrophin-releasing hormone (TRH) induced thyrotrophin (TSH) release was estimated in 19 patients with severe hypothyroidism treated with T4. During PTU medication a significant decrease in serum T3 from 90 \m=+-\16 (sd) to 79 \ m=+-\23 ng/100 ml (P < 0.01) and a reciprocal increase in serum reverse T3 from 51 \m=+-\14 (sd) to 58 \m=+-\20 ng/100 ml (P < 0.025) were found. No significant changes in serum T4, basal serum TSH or response to TRH could be demonstrated. Carbimazole did not change any of the parameters studied. Several animal and in vitro studies have provided evidence that propylthiouracil (PTU) in addition to an intrathyroidal effect inhibits the monodeiodination of thyroxine (T4) and also that of triiodothyronine (T3) (Braverman 8c Ingbar 1962; Morreóle de Escobar 8c Escobar del Rey 1962; Oppenheimer et al. 1972; Frumess 8c Larsen 1975). PTU has also been shown to increase the T4/T3 ratio in the pituitary gland and to increase the thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH) in thyroidectomized rats (Escobar del Rey et al. 1972).Recent studies in man have demonstrated that PTU in contrast to methimazole can reduce the serum levels of T3 in T4-treated hypothyroid patients (Saberi et al. 1975). In a similar study in athyreotic man an increase in TRH-induced

Correlation between antithyroid effect and serum concentrations of propylthiouracil in patients with hyperthyroidism.

“…Several in vitro, animal and human experimental studies have provided evidence that PTU in addition to an intrathyroidal effect on hormone production also inhibits the extrathyroidal conversion of T4 to T3 and of rT3 to T2 (3,3'-diiodothyronine) thus acutely increasing the serum concentration of rT3 and reducing the concentration of T3 (Oppenheimer, Schwartz & Surks, 1972;Saberi, Sterling & Utiger, 1975;Westgren etal., 1977;Laurberg & Weeke, 1978;Siersbaek-Nielsen et al, 1978). These alterations can be explained by an effect of PTU on the 5'-deiodinase of the liver (Kaplan, Schimmel & Utiger, 1977;.…”