抗甲状腺剤による血液障害に関する臨床的ならびに実験的研究 第II編 抗甲状腺剤による血液障害に関する実験的研究

Abstract

In this part, the author attempted experimental studies using rabbits for the purpose of investigating the pathogenesis of the blood disorders induced by anti-thyroid drugs: Rabbits were treated with TSH or thyroid powder in order to simulate the hyperthyroid conditions and treated with methimazole (MEZ). Although the TSH administration for 11 days could not cause consistent hyperthyroidism rabbits treated with thyroid powder for two weeks showed TBCindex of less than 0.5, accompanying elevation of RBC count, which was cancelled by MEZ administration. MEZ alone, too, could decrease the RBC count depending on its dosage. The increase of RBC induced by thyroid powder was abolished also by NMO (nitrogen mustard Noxide)administration for two weeks.In contrast, neutrophil count was decreased by the thyroid powder administration as well as by the MEZ treatment depending on its dosage. Administration of 2mg/kg or 20mg/kg MEZ added after thyroid powder administration intensified the neutrophil depression, while 10mg/kg of MEZ showed no additional effect. Recovery of the neutrophil count was faster in the 10mg/kg group than in the 2 mg/kg or 20 mg/kg group. Addition of NMO did not significantly affect the decrease of neutrophilic granulocyte cells induced by MEZ alone or MEZ after thyroid powder administration.There sults obtained could be summarized as follows:1) The RBC count increased in hyperthyroid rabbits, while the neutrophil count decreased.2) Administration of MEZ alone depressed both RBC and neutrophil counts.3) Concerning the RBC count, the opposing effects of thyroid hor mone and MEZ were cancelled in their combined administration. On the contrary, the neutrophil count was decreased depending on the MEZ doses or the severity of hyperthyroidism, but I could not demonstrate their synergistic effects.4) NMO adm inistration, as far as my experimental design is concerned could not intensify the neutrophil depressen.These experim ental results obtained are consistent with those obtained in hyperthyroid patients receiving anti-thyroid drugs. The reason why most of hyperthyroid patients receiving anti-thyroid drugs do not develop a clinically apparent not show neutropenia should be attributed to the opposing effects of thyroid hormone and MEZ on the thyroid function. It may be speculated that the neutropenia due to anti-thyroid drug occurs in the patients with some hereditary predisposition,1. g. bone marrow dysfunction, although, in these studies, by NMO administration could not prove the significance of such predisposition to the neutropenia.The pathogenesis of agranulocytosis still remains to be proven. However, this study should have clarified, at least to some extent, hyperthyroidism and that of anti-thyroid drug administration in the pathogenesis of the hematological disorder; in hyperthyroid patients receiving anti-thyroid drugs.