Amiodarone bears a structural resemblance to the thyroid hormones thyroxine (T₄) and triiodothyronine (T₃), while containing approximately 37% iodine by weight. Metabolism of amiodarone causes deiodination, which results in the release of up to 50- to 100-fold excess iodine compared with normal daily intake. Amiodarone-induced thyroid dysfunction results from this massive increase in total iodine, as well as alterations in hormone metabolism caused by the drug. While amiodarone can cause either hyper- or hypo-thyroidism, it typically induces hypothyroidism in iodine-sufficient areas such as the United States where the incidence is estimated to range up to 30%. In particular, patients with preexisting thyroid autoimmunity are at increased risk for the development of hypothyroidism while receiving the drug. The acute effects observed after initiating therapy is an increase in thyroid-stimulating hormone (TSH) levels by 20% to 50%, with a decrease in serum T₃ levels by 15% to 20% within the first 2 weeks of therapy. Amiodarone blocks the peripheral conversion of T₄ to T₃ and inhibits the entry of these hormones into peripheral tissue. The resulting symptoms of hypothyroidism include cold intolerance, dry skin, weight gain, and fatigue. In the ICU, signs of hypothyroidism may also manifest when a patient is having difficulty weaning from mechanical ventilation. Once patients are diagnosed, treatment with
levothyroxine should be initiated and amiodarone may be continued if a suitable replacement antiarrhythmic is not available.