What medications can cause hypothyroidism?

Medications That Cause Hypothyroidism

Amiodarone is the most clinically significant medication causing hypothyroidism, occurring in approximately 20% of patients taking this drug, with hypothyroidism being 2-4 times more common than hyperthyroidism. 1, 2

Primary Medications Causing Hypothyroidism

Amiodarone (Most Important)

• Amiodarone causes hypothyroidism through two mechanisms: excess iodine release (37% iodine by weight) that inhibits thyroid hormone synthesis, and direct cytotoxic effects on thyroid cells. 2, 3
• Amiodarone-induced hypothyroidism (AIH) develops in susceptible individuals, particularly those with pre-existing subclinical thyroid disease or positive anti-thyroid antibodies. 4, 3
• The drug inhibits 5'-deiodinase activity, blocking peripheral conversion of T4 to T3, which can contribute to hypothyroid states. 5, 3
• Patients with hypothyroidism who have a strong clinical indication for amiodarone may continue the drug with appropriate thyroid hormone supplementation. 1
• Screening for thyroid disease before starting amiodarone and periodic monitoring (TSH and free T4) during therapy are essential. 1, 3

Lithium

• Lithium inhibits thyroid hormone synthesis and secretion, leading to hypothyroidism in susceptible patients. 6
• This medication requires regular thyroid function monitoring during treatment. 6

Anti-Thyroid Medications

• Propylthiouracil and methimazole can cause hypothyroidism when used to treat hyperthyroidism, particularly with excessive dosing. 1, 6
• In pregnancy, propylthiouracil is preferred in the first trimester due to possible teratogenicity with methimazole. 1

Tyrosine-Kinase Inhibitors

• Medications such as imatinib may cause hypothyroidism, requiring close TSH monitoring in patients receiving these agents. 5
• This represents an increasingly recognized cause of drug-induced thyroid dysfunction with molecular-targeted cancer therapies. 6

Immune Checkpoint Inhibitors

• Anti-PD-1/PD-L1 therapy causes thyroid dysfunction in 5-10% of patients, with combination immunotherapy increasing this risk to 20%. 7
• Even subclinical hypothyroidism warrants treatment consideration in these patients if fatigue or other symptoms are present. 7

Medications That Increase Levothyroxine Requirements

Drugs Affecting Thyroid Hormone Absorption

• Phosphate binders (calcium carbonate, ferrous sulfate, sevelamer, lanthanum) bind to levothyroxine and should be administered at least 4 hours apart. 5
• Bile acid sequestrants (colesevelam, cholestyramine, colestipol) and ion exchange resins decrease levothyroxine absorption; administer levothyroxine at least 4 hours prior. 5
• Proton pump inhibitors, sucralfate, and antacids (aluminum/magnesium hydroxides) reduce gastric acidity needed for levothyroxine absorption. 5
• Orlistat may reduce levothyroxine absorption, requiring monitoring of thyroid function. 5

Drugs Increasing Hepatic Metabolism

• Phenobarbital increases levothyroxine metabolism by inducing UGT enzymes, leading to lower T4 levels and increased replacement requirements. 5
• Rifampin accelerates levothyroxine metabolism, necessitating dose adjustments. 5
• Carbamazepine and phenytoin reduce serum protein binding and increase hepatic degradation of levothyroxine by 20-40%. 5

Drugs Affecting Peripheral Conversion

• High-dose propranolol (>160 mg/day) decreases peripheral conversion of T4 to T3, though patients typically remain clinically euthyroid. 5
• High-dose glucocorticoids (dexamethasone ≥4 mg/day) decrease T3 concentrations by 30% acutely. 5

Medications Affecting Thyroid Hormone Transport

• Estrogen-containing oral contraceptives and estrogens increase thyroxine-binding globulin (TBG), potentially requiring dose adjustments in patients on levothyroxine. 5
• Androgens, anabolic steroids, and glucocorticoids decrease TBG concentration. 5
• Sertraline administration in patients stabilized on levothyroxine may result in increased levothyroxine requirements. 5

Critical Clinical Considerations

Monitoring Requirements

• Any patient starting amiodarone requires baseline thyroid function tests (TSH, free T4) and monitoring every 3-6 months during therapy. 1, 3
• Patients with special vigilance needs include those taking amiodarone who may develop either hyperthyroidism or hypothyroidism. 1
• New atrial fibrillation or exacerbation of ventricular arrhythmias in patients on amiodarone should trigger re-evaluation of thyroid status. 1

Treatment Approach for Drug-Induced Hypothyroidism

• For amiodarone-induced hypothyroidism, levothyroxine replacement is initiated while continuing or discontinuing amiodarone based on cardiac indication. 4, 3
• In patients with concurrent adrenal insufficiency and hypothyroidism, steroids must always be started prior to thyroid hormone to avoid adrenal crisis. 7
• When discontinuing causative medications is not feasible, patients require treatment with thyroid hormone while continuing the offending drug. 6

Common Pitfalls

• Failing to recognize that approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to suppress TSH when medications affecting absorption or metabolism are added. 7
• Not adjusting levothyroxine doses when starting or stopping medications that affect thyroid hormone pharmacokinetics. 5
• Overlooking the need for increased levothyroxine requirements during pregnancy (typically 25-50% increase) in women with pre-existing hypothyroidism. 7, 5