抗甲状腺剤のthyroxine末梢代謝抑制作用に関する検討
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概要
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The effect of propylthiouracil (PTU), methylthiouracil (MTU), mercaptoimidazole and potassium iodide was studied on the metabolism of thyroxine (T<SUB>4</SUB>), and the following results were obtained : <BR>1) Urinary excretion rate of I<SUP>131</SUP> decreased and fecal radioactivity increased after I<SUP>131</SUP>-T<SUB>4</SUB> injection in thyroidection in thyroidectomized rats treated with PTU or MTU. No significant change was observed in the fecal and urinary radioactivity after I<SUP>131</SUP>-T<SUB>4</SUB> injection in thyroidectomized rats treated with mercaptoimidazole or potassium iodide.<BR>2) The turnover rate of injected I<SUP>131</SUP>-T<SUB>4</SUB> decreased in thyroidectomized rats treated with PTU or MTU.<BR>3) Distribution of I<SUP>131</SUP> in the liver and intestines (with contents) increased after 6 hours of I<SUP>131</SUP>-T<SUB>4</SUB> injection in thyroidectomized rats treated with PTU.<BR>4) The <I>in vitro</I> deiodination of I<SUP>131</SUP>-T<SUB>4</SUB> in rat liver homogenate was significantly decreased by PTU or MTU administered <I>in vivo</I>.<BR>5) A decrease in weight gain and an increase in the plasma PBI and I<SUP>131</SUP>-triiodothyronine (I<SUP>131</SUP>-T<SUB>3</SUB>) resin uptake was noted in T<SUB>4</SUB>-maintained thyroidectomized rats after the administration of PTU or MTU for 2 months.<BR>6) When PTU-treated rats were administered with varying doses of T4 in order to prevent goiter formation, doses of T<SUB>4</SUB> adequate to restore PBI to normal failed to prevent goiter completely, while goiter-preventing doses were associated with abormally high PBI values. Serum I<SUP>131</SUP>-T<SUB>4</SUB> resin uptake was well related with PBI.<BR>7) The turnover rate of injected I<SUP>131</SUP>-T<SUB>4</SUB> decreased in euthyroid, hyperthyroid and hypothyroid patients by the administration of PTU or MTU.<BR>8) Fecal excretion of I<SUP>131</SUP> increased after I<SUP>131</SUP>-T<SUB>4</SUB> injection in euthyroid patients administered with PTU or MTU. Urinary I<SUP>131</SUP> decreased in one patient administered with PTU.<BR>9) An increase in the PBI was observed after the administration of PTU for 4 weeks in athyrotic patients treated with desiccated thyroid. No significant change was observed in serun I<SUP>131</SUP>-T<SUB>3</SUB> erythrocyte uptake in these patients.<BR>These results indicate that PTU and MTU inhibit the peripheral metabolism of T<SUB>4</SUB> and that the inhibitory effect may be independent on the the alterations of thyroxine binding capacity of serum proteins since no effect was observed on serum I<SUP>131</SUP>-T<SUB>4</SUB> resin or erythrocyte uptake in these agents. It is suggested that the decrease in degradation of T<SUB>4</SUB> caused by PTU might influence the secretion of TSH.
- 日本内分泌学会の論文