Endocrinology, Vol 127, 1656-1664, Copyright © 1990 by Endocrine Society

ARTICLES

Thyroxine, 3,5,3'-triiodothyronine, and 3,3',5'-triiodothyronine concentrations in several tissues of the rat: effects of amiodarone and desethylamiodarone on thyroid hormone metabolism [corrected] [published erratum appears in Endocrinology 1991 Jan;128(1):393]

JP Schroder-van der Elst and D van der Heide
Department of Metabolic Diseases and Endocrinology, University Hospital, Leiden, The Netherlands.

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.

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