Effects of phenylbutazone on thyroid iodine metabolism in vitro

Several alterations of thyroid function parameters have been reported in patients treated with phenylbutazone and we have studied the effect of this drug on the intrathyroidal iodine metabolism. An inhibition of the iodide transport expressed in terms of T/M ratios was observed in bovine thyroid slices incubated with high phenylbutazone concentrations. 10−3m produced 72% inhibition whereas lower concentrations showed no significant difference as compared with controls. Iodotyrosine synthesis was affected by 10−4m and 10−5m phenylbutazone. Formation of iodothyronine synthesis was markedly affected between 10−4m and 10−7m phenylbutazone concentrations. Thyroid peroxidase activity was measured by tyrosine-iodinase, triiodide and guaiacol assays. Soluble, pseudosolubilized and crude peroxidase preparations from bovine glands, as well as the soluble enzyme from human thyroids, have shown inhibition of tyrosine-iodinase activity when incubated with phenylbutazone in concentrations ranging from 10−3m to 10−8m, with a Ki of 4 × 10−6m for bovine thyroid peroxidase and of 6 × 10−6m for human soluble peroxidase. Formation of triiodide was affected between 10−3m and 10−8m phenylbutazone concentrations. Guaiacol peroxidation was scarcely affected by the action of the drug. We have concluded that phenylbutazone affects the intrathyroidal iodine metabolism through the inhibition of thyroid peroxidase in concentrations which are usually present in the sera of patients treated with this drug.