Amiodarone-induced thyrotoxicosis and hypothyroidism

Amiodarone is a benzofuranic-derivative iodine-rich drug widely used for the treatment of refractory tachyarrhythmias. It often causes changes in thyroid function tests (typically an increase in serum thyroxine, T-4, and reverse triiodothyronine, rT3, and a decrease in serum triiodothyronine, T3, concentrations), mainly related to the inhibition of 5'-deiodinase activity. In 14-18% of amiodarone-treated patients, there is overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH). Both AIT and AIH may develop either in apparently normal thyroid glands or in glands with preexisting disease. The pathogenesis of AIH is related to a failure to escape from the acute Wolff-Chaikoff effect due to defects in thyroid hormonosynthesis, and, in patients with positive thyroid autoantibody tests, to concomitant autoimmune thyroiditis. AIT is primarily related to excess iodine-induced thyroid hormone synthesis in an abnormal thyroid gland (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), although mixed forms frequently exist. Treatment of AIH consists of L-T4 replacement while continuing amiodarone therapy; alternatively, if feasible, amiodarone can be discontinued, especially in the absence of thyroid abnormalities, and the natural course towards euthyroidism can be accelerated by a short course of potassium perchlorate administration. In type I AIT the main medical treatment consists of the simultaneous administration of thionamides and potassium perchlorate, while in type II AIT glucocorticoids are the most useful therapeutic option. Mixed forms are best treated with a combination of thionamides, potassium perchlorate and glucocorticoids. Radioiodine therapy is usually not feasible due to the low thyroidal radioiodine uptake, while thyroidectomy can be performed in cases resistant to medical therapy or in those requiring a rapid control of thyrotoxicosis after a short course with iopanoic acid to restore normal serum T-3 levels.