NONGOITROUS (TYPE-I) AMIODARONE-ASSOCIATED THYROTOXICOSIS - EVIDENCE OF FOLLICULAR DISRUPTION IN-VITRO AND IN-VIVO

Treatment with the antiarrhythmic agent amiodarone results in alterati ons in thyroid hormone metabolism, and can induce either hypothyroidis m or hyperthyroidism (amiodarone-associated thyrotoxicosis, AAT). AAT occurs in patients both with and without preexisting goiter, In our st udy of the nongoitrous variety, the effect in vitro of amiodarone trea tment and of concurrent treatment with potential inhibitors on thyroid cells (FRTL-5) was assessed by measuring the release of radiolabeled chromium (Cr-51). In addition, thyroid histopathology was evaluated in autopsy specimens from six amiodarone-treated patients who had no pre treatment evidence of thyroid disease, Histopathologic examination rev ealed minimal or no evidence of thyroid follicular damage in specimens from amiodarone-treated euthyroid patients (n = 4). In contrast, mode rate to severe follicular damage and disruption were present in glands from patients with AAT (n = 2). Studies in vitro showed amiodarone to be cytotoxic to thyroid cells; this effect was inhibited by treatment with dexamethasone (10(-3) mmol) or perchlorate (2.5 mu g/mL). In sum mary, we demonstrate evidence in vitro and in vivo of amiodarone-induc ed thyroid follicular damage and disruption in specimens from patients with nongoitrous AAT and in cultured normal thyroid cells, In additio n, we demonstrate inhibition of this effect following treatment in vit ro with dexamethasone or perchlorate, Our findings support the concept that nongoitrous (type I) AAT results from direct drug toxicity with disruption of thyroid follicles and subsequent release of preformed th yroid hormone.