Amiodarone-induced thyroid dysfunction: diagnostic role of free serum thyroid hormone levels and pathogenetic significance of antithyroid antibodies.

Forty-six patients treated with amiodarone hydrochloride for a mean period of 41 +/- 3.5 months, with an average daily dose of 240 +/- 57 mg/day, have been studied. Thyroid function was assessed clinically and by laboratory tests, which included free-triiodothyronine (free-T3), free-thyroxine (free-T4) and thyrotropin. Antimicrosomal and antithyroglobulin antibodies were also looked for. Three patients (6.5%) were found to be hyperthyroid and two (4.3%) hypothyroid. Of the 41 clinically euthyroid patients, 19 (46.3%) showed one or more abnormalities in the thyroid function tests. In this group, only free-T4 was found significantly increased (p less than 0.05) as compared to both control populations. Antimicrosomal antibodies (titre greater than or equal to 1:1600) were present in 4 of 41 (9.7%) euthyroid patients, but not in hyper- or hypothyroid patients. There were no antithyroglobulin antibodies in any patients. Free hormone measurements have proved to significantly correlate with the clinical picture. Increases in free-T3 and free-T4 are the main features of hyperthyroidism, while a reduction in free-T4 serum level was specific for hypothyroidism. There are probably several mechanisms responsible for hyperthyroidism and some genetically controlled defects in synthesis and release of thyroid hormones might be among these. The presence of antithyroid antibodies could be due to deposits of amiodarone in the thyroid gland, with a consequent release of antigen from the follicle cell, but only in those patients with genetically determined defects in immunological surveillance could an autoimmune thyroiditis, with consequent hypothyroidism, develop.