Literature
Clinical Pearls & Morning Reports
Published August 21, 2019
What are some of the effects of amiodarone on thyroid function and thyroid laboratory testing?
There is a growing list of medications known to adversely affect thyroid function or interpretation of the results of standard thyroid laboratory testing. Read the review article here.
Clinical Pearls
Q: What are some of the drugs that exert suppressive effects on thyrotropin release without appreciably affecting circulating T4 levels?
A: Several categories of drugs exert suppressive effects on thyrotropin release without appreciably affecting circulating T4 levels, including glucocorticoids, dopamine agonists, somatostatin analogues, and metformin. Although thyrotropin suppression in patients receiving these agents is usually metabolically insignificant, a low thyrotropin level with a normal free T4 level may be confused with subclinical hyperthyroidism, prompting unnecessary evaluation or treatment.
Q: What are some of the drugs that lead to increases in thyroxine-binding globulin?
A: Several drugs lead to increases in thyroxine-binding globulin, including oral estrogen and selective estrogen-receptor modulators, methadone, heroin, mitotane, and fluorouracil. Conversely, reductions in this protein occur with the use of androgens, glucocorticoids, and niacin. The most common and clinically relevant changes in thyroxine-binding globulin occur with the use of estrogen-containing drugs in patients receiving thyroid hormone replacement therapy. In such patients, increases in protein binding lead to additional binding of T4, even in the presence of low free T4 levels. Consequently, patients dependent on exogenous thyroid hormone will have an increased dose requirement after the initiation of oral estrogen treatment.
Morning Report Questions
Q: What are some of the effects of amiodarone on thyroid function and thyroid laboratory testing?
A: Amiodarone, a class III antiarrhythmic agent, is 37.3% iodine by weight and undergoes partial deiodination, releasing approximately 7 mg of iodide per 200-mg tablet, which is roughly 45 times the recommended daily intake of 150 μg for men and nonpregnant women. In addition to inducing hypothyroidism in susceptible patients, iodine from amiodarone causes hyperthyroidism in some patients, a disorder known as type 1 amiodarone-induced thyrotoxicosis. In addition to causing true hypothyroidism and thyrotoxicosis, amiodarone leads to predictable changes in thyroid laboratory test results in euthyroid persons. Inhibition of peripheral and central T4-to-T3 conversion by amiodarone and its major active metabolite, desethylamiodarone, leads to reductions in circulating and intrapituitary T3 levels, thereby stimulating thyrotropin-releasing hormone and thyrotropin release through an absence of negative feedback. Increases in thyrotropin prompt thyroidal release of T4, which accumulates further because of inhibited conversion to T3. The net effect of these changes is a serum thyrotropin level that is elevated or at the high end of the normal range, high levels of total and free T4, and a T3 level at the low end of the normal range in a euthyroid patient.
Q: What adverse effects can immune checkpoint inhibitors have on thyroid function?
A: Immune checkpoint inhibitors, including those that inhibit cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) receptor, have a variety of adverse endocrine effects. Hypophysitis occurs more frequently in patients taking CTLA-4 inhibitors, whereas primary thyroid dysfunction is seen more often with PD-1 inhibitors. Primary thyroid dysfunction is noted variably in the literature as affecting approximately 5 to 10% of patients treated with CTLA-4 inhibitors, 10 to 20% of those treated with PD-1 inhibitors, and more than 20% of patients treated with combination therapy. Most patients receiving such therapy for cancer have painless thyroiditis, presenting with transient thyrotoxicosis followed by hypothyroidism. Hypothyroidism ensues 10 to 20 weeks after the initiation of therapy and is often irreversible.