Some oral cholecystographic agents and the antiarrhythmic medication amiodarone are excreted slowly and can be associated with more prolonged decreases in thyroid hormone production. Iodide and medications containing iodide may precipitate a longer enduring hypothyroidism in patients with chronic autoimmune thyroiditis and in those with hyperthyroidism who have received radioactive iodine therapy or have undergone partial thyroidectomy.
The cholesterol-lowering bile acid sequestrants colestipol and cholestyramine can also inhibit thyroid reabsorption from the intestine, potentially leading to hypothyroidism. Patients dependent on exogenous T4 or who have an underlying decreased thyroid function may develop hypothyroidism.
Table 3
WHICH MEDICATIONS CAN CAUSE THYROID DYSFUNCTION?
| Drugs that increase thyroid hormone secretion Iodide-containing medication Amiodarone Providone-iodine antiseptics X-ray contrast media containing iodine | Drugs that increase hepatic metabolism of T4 and T3 Phenobarbital Rifampin Phenytoin Carbamazepine |
| Drugs that decrease TBG,* causing a relative increase in unbound thyroid Androgens Anabolic steroids | Drugs that decrease T4 absorption Colestipol Cholestyramine Aluminum hydroxide Ferrous sulfate Sucralfate |
| Drugs that decrease thyroid hormone secretion Lithium carbonate Iodide Amiodarone | Drugs that increase TBG,* causing a relative decrease in unbound thyroid Estrogens Tamoxifen Heroin and methadone |
| *Thyroxine-binding globulin Table adapted from: Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med 1995;333(25):1688-94. | |
Drugs that alter thyroid hormone metabolism can also be problematic. Although thyroid hormone is metabolized mostly by deiodination, it also undergoes glucuronidation and sulfation. Phenobarbital, rifampin, phenytoin, and carbamazepine all increase T4 and T3 metabolism by inducing these hepatic enzymes. In patients with no thyroid disease, phenytoin and carbamazepine can decrease circulating free T4 levels by 20% to 40%.12 Patients receiving T4 replacement may need their dosage increased or risk hypothyroidism if placed on one of these medications (Table 3).
Several medications alter total T4 and T3 levels by increasing or decreasing thyroid-binding proteins. Examples include estrogens, androgens, anabolic steroids, methadone, and heroin. Most thyroid hormone circulates as bound, but it is the unbound form that is active in peripheral tissues. Patients thus can experience changes in the binding proteins, while the proportion of unbound (“free”) hormone at the tissue level remains unaffected.
Because this unbound form remains relatively unchanged, the patient with normal thyroid function remains euthyroid despite alterations in total thyroid levels. When patients with hypothyroidism start one of these medications, their replacement hormone dosage may need to be adjusted.
Related resources
- American Association of Clinical Endocrinologists. www.aace.com
- Clinical practice guidelines for evaluation and treatment of hypothyroidism and hyperthyroidism. Position statement on subclinical hypothyroidism and pregnancy
- Thyroid Federation International. www.thyroid-fed.org
- Online videos regarding thyroid disease (patient-directed). Patient handouts on thyroid disease
- Jameson JL, Weetman AP. Disorders of the thyroid gland. In: Harrison’s Principles of Internal Medicine. 15th ed. New York: McGraw-Hill; 2001:2060-84
Drug brand names
- Amiodorone • Pacerone, Cordarone
- Colestipol • Colestid
- Methimazole • Tapazole
- Olanzapine • Zyprexa, Zyprexa Zydis
- Rifampin • Rifadin, Rimactane
Disclosure
The author reports no financial relationship with any company whose products are mentioned in this article.