The Effects of Amiodarone on Serum Thyroid Hormones and Hepatic Thyroxine 5′-Monodeiodination in Rats*

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Abstract
Amiodarone (2-n-butyl-3,4''-diethylaminoethoxy-3'',5''-diiodobenzoyl-benzofurane) is an antiarrhythmic drug which increases serum T4 [thyroxine] and rT3 [reverse triiodothyronine] levels in patients and lowers serum T3 [triiodothyronine] levels. To investigate its effects on T4 metabolism and its cardiac action, amiodrane was fed to male Fisher rats at doses of 5, 15, and 45 mg/kg body wt .cntdot. day; controls received potassium iodide for 4-7 wk, and another group received sodium ipodate. At 4 wk, amiodarone caused a dose-dependent increase in the serum T4 concentration and a slight reduction of serum TSH without a change in the serum T3 concentration. These changes were not present at 7 wk. Sodium ipodate raised serum T4 concentrations at both times. Rats treated with T4 (150 .mu.g/kg body wt .cntdot. day) to suppress thyroidal secretion of hormone and with amiodarone (15 mg/kg) had marked reduction of serum T3 concentrations compared with controls receiving T4 without amiodarone. Liver homogenates from rats treated with amiodarone showed marked reduction on T4 5''-monodeiodinase activity in a dose-related manner. Amiodarone added to liver homogenates in vitro at concentrations of 0.001-1 mM did not inhibit T3 production from T4, whereas ipodate added in vitro (0.01-1 mM) did inhibit T3 production. Rats treated with amiodarone showed a lowering of the resting heart rate and a reduction of the increment in heart rate after i.v. isoproterenol administration. The cardiac Ca2+ myosin ATPase activity was reduced in rats receiving amiodarone (45 mg/kg) compared with that in controls. Rats treated with amiodarone have reduced peripheral conversion of T4 to T3 owing to impaired hepatic T4 5''-monodeiodinase activity. In addition, these rats have slowing of heart rate and reduction of cardiac Ca2+ myosin ATPase activity. Amiodarone apparently blocks some effects of thyroid hormone on the heart, but additional studies are needed to test this hypothesis.

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