Effects of desethylamiodarone on thyroid hormone metabolism in rats: comparison with the effects of amiodarone.

Desethylamiodarone is the principal metabolite of amiodarone. Amiodarone is a class III antiarrhythmic agent, which acts by lengthening repolarization in the myocardium, an effect that is identical to that produced by hypothyroidism. Amiodarone is known to alter thyroid hormone metabolism, and it has been suggested that the mechanism underlying its antiarrhythmic action is the induction of a myocardial but not generalized hypothyroidism. Since the serum levels of desethylamiodarone reach those of the parent compound during chronic amiodarone therapy, it has been suggested that at least part of amiodarone's pharmacological effects may be attributable to the additive effects of the metabolite. Therefore, we investigated the effects of desethylamiodarone on thyroid hormone metabolism and compared them with those of amiodarone in rats. We have shown that chronic treatment with desethylamiodarone decreased serum T3, markedly increased serum reverse T3 with no significant change in serum T4. These effects are similar to those of amiodarone. The data suggest that the chronic effects of amiodarone on thyroid hormone metabolism may be due at least in part to the actions of desethylamiodarone.