Pharmacotherapy Newsletter

Volume 1, Issue 40, 10/19/2009

Question

How does amiodarone (Cordarone®), a class III antiarrhythmic, cause hyperthyroidism and what are the clinical implications?

Answer

Amiodarone (Cordarone®) is a commonly prescribed medication for the management of both atrial and ventricular arrhythmias.^1,2  Unfortunately, when amiodarone is given to a euthyroid (normal thyroid function) patient , the normal physiologic process for the formation of the thyroid hormones, thyroxine (T4) and 3,5,3'-triiodothyronine (T3), can be adversely affected.  The following are the generalized steps for normal thyroid hormone production (i.e., a euthyroid patient not on amiodarone): thyroid releasing hormone (TRH) is secreted from the hypothalamus to stimulate the anterior pituitary gland to release thyroid stimulating hormone (TSH); the TSH then travels to the thyroid gland where it causes an increase in production of thyroglobulin and the enzyme thyroid peroxidase; iodide ingested from food or water enters into the thyroid follicular cell via the Na⁺/I^- cotransporter; once the iodide is inside the thyroid follicle cell it is transported into the follicular lumen via the pendrin transporter.  The iodide is oxidized by thyroid peroxidase into iodine which is then able to iodinate the tyrosine residues within the thyroglobulin to form both monoiodotyrosine and diiodotyrosine.  These products combine to form T4 and T3 and then undergo proteolysis and exocytosis for secretion and recycling (see figure 1).