Imatinib induces hypothyroidism in patients receiving levothyroxine

• Published in: Clinical pharmacology and therapeutics Vol. 78; no. 4; p. 433
• Main Authors: de Groot, Jan Willem B, Zonnenberg, Bernard A, Plukker, John T M, van Der Graaf, Winette T A, Links, Thera P
• Format: Journal Article
• Language: English
• Published: United States 01.10.2005
• Subjects: Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Benzamides; Carcinoma, Medullary - drug therapy; Carcinoma, Medullary - surgery; Drug Synergism; Female; Gastrointestinal Stromal Tumors - drug therapy; Humans; Hypothyroidism - chemically induced; Imatinib Mesylate; Male; Middle Aged; Piperazines - adverse effects; Piperazines - pharmacology; Pyrimidines - adverse effects; Pyrimidines - pharmacology; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - surgery; Thyroidectomy; Thyrotropin - blood; Thyroxine - adverse effects; Thyroxine - blood; Thyroxine - pharmacokinetics; Triiodothyronine - blood
• ISSN: 0009-9236
• DOI: 10.1016/j.clpt.2005.06.010

Interactions of imatinib with other drugs have been scarcely reported. We report a previously unknown effect of imatinib on levothyroxine therapy. Eleven patients (1 with gastrointestinal stromal tumor and 10 with medullary thyroid carcinoma) received imatinib. Eight had undergone thyroidectomy and used levothyroxine, and 3 had the thyroid in situ. Thyroid function was measured before, during, and within 2 weeks after any change in either imatinib or levothyroxine dosage. We observed symptoms of hypothyroidism in all patients who had undergone thyroidectomy, whereas patients with the thyroid in situ remained clinically and biochemically euthyroid. On average, thyrotropin (INN, thyrotrophin) levels increased to 384% +/- 228% of the upper limit in patients after thyroidectomy, whereas free thyroxine (fT4) and free tri-iodothyronine (fT3) values remained within the reference range (59% +/- 17% of the upper limit for fT4 and 63% +/- 4% of the upper limit for fT3). Clinicians should be aware that hypothyroid subjects receiving imatinib have a high likelihood for increased levothyroxine replacement and should be closely monitored for elevations in thyrotropin indicating worsening hypothyroidism.