title: Imatinib induces hypothyroidism in patients receiving levothyroxine.
abstract: 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.
authors.affiliation: Department of Endocrinology, University Medical Centre Groningen, Groningen, and Department of Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jan Willem B
authors.initials: JW
authors.lastname: de Groot
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Zonnenberg
authors.forename: John T M
authors.initials: JT
authors.lastname: Plukker
authors.forename: Winette T A
authors.initials: WT
authors.lastname: van Der Graaf
authors.forename: Thera P
authors.initials: TP
authors.lastname: Links
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001549:Benzamides; D018276:Carcinoma, Medullary / Q000188:drug therapy / Q000601:surgery; D004357:Drug Synergism; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects* / Q000494:pharmacology; D011743:Pyrimidines / Q000009:adverse effects* / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000601:surgery; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D014284:Triiodothyronine / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D014284:Triiodothyronine; D000068877:Imatinib Mesylate; D013972:Thyrotropin; D013974:Thyroxine