No abstract

No abstract

The effect of phenobarbital (PB) and/or thyroxine on the thyroidal accumulation and oxidation of [35S]methimazole (MMI) and serum TSH levels was studied in rats. PB treatment increased the accumulation of MMI and the serum TSH levels, but concurrent administration of T4 reversed these effects. It was concluded that increased TSH secretion in PB-treated animals was likely to be the major mechanism involved in the increased MMI accumulation. PB also increased the intrathyroidal oxidation of MMI to sulphate. However, in contrast to the PB effect on accumulation, concurrent T4 administration only partially reversed the effect on oxidation. The results suggested that the increased oxidation of MMI in PB-treated animals was due to a direct effect of PB or possibly a combination of this direct effect and the indirect TSH effect. Possible mechanisms postulated for a direct effect were thyroidal microsomal enzyme induction and/or changes in thyroidal protein binding of MMI.

Chronic treatment of intact rats with various doses of TSH increased the thyroidal 35S accumulation after single doses of [35S]methimazole (MMI) and [35S]propylthiouracil (PTU). However, no effect on the intrathyroidal breakdown of the drugs was observed. Thus absolute thyroidal levels of unmetabolized MMI and PTU were increased by factors of up to 2 and 3, respectively, compared to the control groups. Simultaneous decreases in the levels of thyroidal total iodine were observed. Hypophysectomized rats showed a marked inhibition of both thyroidal accumulation and oxidation of [35S]-MMI but TSH treatment of hypophysectomized rats restored the accumulation and oxidation to sham-operated and control group levels. The results show that in rats TSH has an important role in the control of thyroidal levels of antithyroid drugs currently used in the treatment of hyperthyroidism.

No abstract