What medications can increase Thyroid-Stimulating Hormone (TSH) levels?

Medications That Increase TSH Levels

Multiple medications can increase TSH levels by interfering with thyroid hormone synthesis, absorption, metabolism, or by inducing thyroid dysfunction through various mechanisms.

Medications That Decrease Levothyroxine Absorption (Leading to Elevated TSH)

Phosphate Binders and Iron Supplements

• Calcium carbonate, ferrous sulfate, sevelamer, and lanthanum can bind to levothyroxine and prevent its absorption, resulting in elevated TSH levels 1
• These agents should be administered at least 4 hours apart from levothyroxine to avoid this interaction 1

Bile Acid Sequestrants and Ion Exchange Resins

• Colesevelam, cholestyramine, colestipol, and kayexalate are known to decrease levothyroxine absorption, leading to inadequate thyroid hormone replacement and elevated TSH 1
• Levothyroxine should be administered at least 4 hours prior to these medications 1

Gastrointestinal Medications

• Proton pump inhibitors, sucralfate, and antacids (aluminum and magnesium hydroxides, simethicone) reduce levothyroxine absorption by causing hypochlorhydria and affecting intragastric pH 1
• Gastric acidity is essential for adequate levothyroxine absorption 1
• Orlistat can interfere with levothyroxine absorption, requiring monitoring of thyroid function in patients taking both medications 1

Medications That Increase Hepatic Metabolism of Levothyroxine

Enzyme Inducers

• Phenobarbital increases levothyroxine metabolism by inducing uridine 5'-diphospho-glucuronosyltransferase (UGT), leading to lower T4 serum levels and elevated TSH 1, 2
• Rifampin accelerates the metabolism of levothyroxine, resulting in increased levothyroxine requirements and potentially elevated TSH if the dose is not adjusted 1
• Carbamazepine and phenytoin stimulate hepatic microsomal enzyme activity, causing increased hepatic degradation of levothyroxine and potentially elevated TSH 1

Medications That Directly Induce Hypothyroidism

Lithium

• Lithium inhibits the synthesis and/or release of thyroid hormones, making it one of the most common causes of drug-induced hypothyroidism 3
• Thyroid function should be evaluated prior to initiating lithium therapy 3

Amiodarone

• Amiodarone can cause hypothyroidism through multiple mechanisms, including inhibition of thyroid hormone synthesis and peripheral conversion of T4 to T3 1, 3
• While amiodarone may cause isolated biochemical changes in clinically euthyroid patients, it can also induce frank hypothyroidism with elevated TSH 1

Interferon and Cytokines

• Interferon therapy can induce hypothyroidism through immune mechanisms, including the development of thyroiditis 3
• Thyroid function should be evaluated before starting interferon treatment 3

Tyrosine Kinase Inhibitors

• Tyrosine kinase inhibitors and drugs blocking vascular endothelial growth factor receptors can induce thyroiditis, leading to hypothyroidism with elevated TSH 3

Immune Checkpoint Inhibitors

• Anti-CTLA4 and anti-PD-1 antibody drugs can cause central hypothyroidism through immunological mechanisms, though they more commonly cause primary hypothyroidism 3
• Thyroid dysfunction occurs in 6-9% of patients on anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy 4

Antithyroid Medications

• Propylthiouracil and methimazole inhibit thyroid hormone synthesis by interfering with thyroid peroxidase-mediated iodination 5
• While these are used therapeutically for hyperthyroidism, excessive doses can cause hypothyroidism with elevated TSH 5

Medications That May Affect TSH Through Other Mechanisms

Glucocorticoids

• High-dose glucocorticoids (dexamethasone ≥4 mg/day) can decrease peripheral conversion of T4 to T3, though they may also suppress TSH through central mechanisms 1
• Long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production 1

Bexarotene

• Bexarotene can cause central hypothyroidism by inhibiting TSH secretion, leading to low thyroid hormone levels despite inappropriately normal or low TSH 3

Critical Clinical Considerations

• When TSH becomes elevated in patients taking levothyroxine, always review medication lists for potential drug interactions before simply increasing the levothyroxine dose 4, 1
• Timing of levothyroxine administration is crucial—it should be taken on an empty stomach and separated from interfering medications by at least 4 hours 1, 2
• Monitor TSH levels 6-8 weeks after starting any medication known to affect thyroid function in patients with hypothyroidism 4
• Evaluate thyroid function before prescribing medications with known thyroid effects, including amiodarone, lithium, interferon, and biological therapies 3