Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy

Abstract

Amiodarone induces predictable changes in thyroid function tests that are largely explicable in terms of the physiological effects of iodide excess and inhibition of deiodinase activity. Clinically relevant thyroid dysfunction is not uncommon during amiodarone therapy, and requires careful diagnosis and treatment. The diagnosis and management of thyrotoxicosis is probably best supervised by a specialist endocrinologist. Control of hypothyroidism can generally be achieved simply by the addition of T4 to the therapeutic regimen, ideally after an initial assessment by an endocrinologist. The frequency with which amiodarone causes thyroid and other complications serves to emphasize the need for rational prescribing and long-term cardiological follow up.

Figure 1

Structure of amiodarone and thyroid hormones.

Figure 2

Synthetic pathway of thyroid hormones. The organification of oxidised iodine takes place at the apical membrane of the thyrocyte and involves iodination of tyrosine residues on thyroglobulin (TG) molecules stored in the thyroid follicular colloid. Monoiodotyrosine (MIT) residues and diiodotyrosine (DIT) residues within the same and adjacent thyroglobulin molecules then combine to form triiodothyronine (T₃, the major biologically active hormone), thyroxine (T₄), and, to a limited extent, the inactive compound reverse triiodothyronine (rT₃). Thyroid hormones are cleaved from thyroglobulin after pinocytosis of colloid into the thyrocyte, and are then released into the circulation. The thyroid gland is the only source of circulating T₄, whereas 80% of circulating T₃ is generated by deiodination of T₄ in peripheral tissues, especially the liver. The sites of action of antithyroid drugs are highlighted. TPO, thyroid peroxidase; I*, oxidised form of iodide.

Figure 3

Suggested protocol for screening thyroid function in patients treated with amiodarone. TPO, thyroid peroxidase; * amiodarone withdrawal considered an alternative option in some cases.