Schröder-van der Elst J P, van der Heide D
Department of Metabolic Diseases and Endocrinology, University Hospital, Leiden, The Netherlands.
Endocrinology. 1990 Oct;127(4):1656-64. doi: 10.1210/endo-127-4-1656.
The effects of amiodarone, an iodinated antiarrhythmic drug, on thyroid hormone metabolism are known. It is not known whether the main metabolite, desethylamiodarone, is responsible. We investigated the influence of both compounds on the intracellular rT3, T4, and T3 concentrations in tissues of the rat, the source of T3 (plasma-derived vs. produced locally from T4) and T3 and T4 production by the thyroid. Special attention is paid to the heart. We found that both amiodarone and desethylamiodarone cause a decrease in intracellular T3 in all tissues (P less than 0.001), in most tissues an increase in T4 and a greater increase in the rT3 concentration. Both compounds inhibit both deiodination (P less than 0.0001) and T3 production by the thyroid (P less than 0.0001); T4 production was enhanced (P less than 0.05). In the heart a hypothyroid-like state, caused by decreased plasma-derived T3 (P less than 0.0001), was found. But a pool of T3 produced locally from T4 was present (21% of the total T3, P less than 0.01), which has never been demonstrated under normal conditions. This pool might play a role in the mechanism of action of the drugs. Differences between the drugs were organ-specific, but the effects of desethylamiodarone were as strong as or stronger than those of amiodarone. We conclude that desethylamiodarone was responsible for the changes, although the possibility of a common metabolite, generated later, has not been excluded.
含碘抗心律失常药物胺碘酮对甲状腺激素代谢的影响已为人所知。但其主要代谢产物去乙基胺碘酮是否起作用尚不清楚。我们研究了这两种化合物对大鼠组织细胞内反三碘甲状腺原氨酸（rT3）、甲状腺素（T4）和三碘甲状腺原氨酸（T3）浓度的影响，T3的来源（血浆来源与由T4局部产生）以及甲状腺对T3和T4的生成情况。特别关注了心脏。我们发现，胺碘酮和去乙基胺碘酮均导致所有组织细胞内T3减少（P<0.001），在大多数组织中T4增加，rT3浓度增加得更多。两种化合物均抑制脱碘作用（P<0.0001）和甲状腺对T3的生成（P<0.0001）；T4生成增加（P<0.05）。在心脏中发现了一种类似甲状腺功能减退的状态，这是由血浆来源的T3减少所致（P<0.0001）。但存在由T4局部产生的T3池（占总T3的21%，P<0.01），这在正常情况下从未被证实过。这个T3池可能在药物作用机制中发挥作用。两种药物的差异具有器官特异性，但去乙基胺碘酮的作用与胺碘酮一样强或更强。我们得出结论，去乙基胺碘酮是导致这些变化的原因，尽管尚未排除后期产生共同代谢产物的可能性。
