title: Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity.
abstract: OBJECTIVE
  Sunitinib is a novel tyrosine kinase inhibitor with antitumor and antiangiogenic effects. An observed higher than expected rate of hypothyroidism in sunitinib-treated patients prompted assessment of the incidence of hypothyroidism.
  
  
  METHODS
  Patients taking sunitinib had their thyroid function tests (TFTs) assessed via chart review. To explore potential effects on the thyroid, we examined the antiperoxidase activity of sunitinib by in vitro testing its effect on guaiacol oxidation and protein iodination by lactoperoxidase.
  
  
  RESULTS
  Of the 89 patients who took sunitinib, 49 patients were excluded from analysis for several reasons. Of the remaining 40 patients, 21 (53%, 24% of the original 89) developed elevated thyrotropin (TSH) after a median of 5 months (range 1-36 months). Median TSH was 21.4 mU/L (range 4.6-174 mU/L). In vitro, sunitinib had antiperoxidase activity that was about one-fourth the potency of propylthiouracil.
  
  
  CONCLUSIONS
  Of the 40 patients who had TFTs assessed after starting sunitinib, 53% developed elevated TSH. We recommend that all patients treated with sunitinib be monitored for hypothyroidism. The mechanism of the antithyroid effect appears to be inhibition of peroxidase activity. Further research is needed to confirm the mechanism by which sunitinib induces hypothyroidism.
authors.affiliation: Endocrinology and Diabetes Division, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Wong
authors.forename: Lee S
authors.initials: LS
authors.lastname: Rosen
authors.forename: Marilyn
authors.initials: M
authors.lastname: Mulay
authors.forename: Andy
authors.initials: A
authors.lastname: Vanvugt
authors.forename: Melissa
authors.initials: M
authors.lastname: Dinolfo
authors.forename: Chisato
authors.initials: C
authors.lastname: Tomoda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sugawara
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Hershman
mesh_terms: D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D007211:Indoles / Q000009:adverse effects*; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000009:adverse effects*; D012189:Retrospective Studies; D000077210:Sunitinib; D013960:Thyroid Function Tests
chemical_list: D007211:Indoles; D011758:Pyrroles; D007453:Iodide Peroxidase; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib