No abstract

A B S T R A C T 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 Ag 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 Ag 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 Ta, 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 Ta (28±5.1 ng/100 ml, mean ±SEM, P < 0.05), whereas serum T4 and rTs increased (1.4± 0.4 /g T4/100 ml, NS and 82.7±9.3 ng rTs/100 ml, P < 0.01). The control study with an equal amount of inorganic iodine did not induce these opposite changes but slightly lowered serum rTs, T3, and T4. In the third study, serum rTs 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 Ts and inducing a preferential production of rT3.Received for puiblication 20 August 1975 and in rezised form 15 March 1976.Amiodarone also increased the response of TSH to TRH. The maximal increment of serum TSH above base line was 32±4.5 oU/ml under treatment and 20±3 AU/ml before treatment (P < 0.01). During this test, the serum Ts increase was more pronounced than during the control period (83±+13 and 47+7.4 ng/100 ml, P < 0.05).

Thyroid function was studied for 42 days in 58 patients, 28 of whome had euthyroid goiter, after urography (diatrizoic acid), cholangiography (ioglycamic acid), and cholecystography (Naiopanoate). After urography and cholangiography short-lived increases of the serum thyroxine occurred in a few patients, but the mean thyroxine and triiodothyronine concentration did not change. By contrast, 7 days after oral cholecystography serum thyroxine had risen consistently by 22% with a concomittant rise of the free thyroxine, while triiodothyronine declined by 15%. The thyroxine metabolite 3,3',5'-triiodo-1-thyronine (reverse T3) rose by 50% and serum thyrotropin concentration doubled. After 42 days thryoxine and triiodothyronine had returned to baseline, and none of the 58 patients developed clinical hyperthyroidism. In patients with severe myxoedema kept on a constant replacement dose with 1-thyroxine NA-iopanoate produced similar changes with the exception of the rise of the serum thyroxine. The primary event after Na-iopanoate seems to be a fall of the serum triiodothyronine, which in turn augments thyrotropin and indirectly thyroxine secretion. the marked and sometimes sustained rose of serum thyroxine after cholecystography may lead to the erroneous diagnosis of hyperthyroidism.