2-n-Butyl-3-(4'-diethylaminoethoxy-3',5'-diiodobenzoyl)-benzofurane (amiodarone), a drug used in arrythmias and angina pectoris, contains 75 mg of organic iodine/200 mg active substance. Four studies were performed to test its effect on thyroid hormone metabolism: (a) nine male subjects were treated with 400 mg of amiodarone for 28 days; (b) five male subjects received, for the same period of time, 150 mg of iodine in the form of Lugol's solution; (c) five subjects received 300 mug L-thyroxine (T4) for 16 days; from the 10th to the 16th day, 400 mg of amiodarone was added; and (d) five euthyroid subjects received 300 mug L-T4 for 16 days. The changes in serum thyroid-stimulating hormone (TSH), serum total T4, 3,5,3'-triiodothyronine (T3), free T3, and 3,5',3'-triiodothyronine (reverse T3, rT3) were measured, and the pituitary reserve in TSH was evaluated by a thyrotropin-releasing hormone (TRH) test. The results show that amiodarone induced a decrease in serum T3 (28+/-5.1 ng/100 ml, mean+/-SEM, P less than 0.0S and 82.7+/-9.3 ng rT3/100 ml, P less than 0.01). The control study with an equal amount of inorganic iodine did not induce these opposite changes but slightly lowered serum rT3, T3, and T4. In the third study, serum rT3 increased as under amiodarone treatment, thereby proving that these changes were peripheral. It is suggested that amiodarone changes thyroid hormone metabolism, possibly by reducing deiodination of T4 to T3 and inducing a preferential production of rT3. Amiodarone also increased the response of TSH to TRH. The maximal increment of serum TSH above base line was 32+/-4.5 muU/ml under treatment and 20+/-3 muU/ml before treatment (P less than 0.01). During this test, the serum T3 increase was more pronounced than during the control period (83+/-13 and 47+/-7.4 ng/100 ml, P less than 0.05).
A Burger, D Dinichert, P Nicod, M Jenny, T Lemarchand-Béraud, M B Vallotton
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