title: Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors.
abstract: BACKGROUND
  Sunitinib malate is an oral tyrosine kinase inhibitor recently approved for the treatment of gastrointestinal stromal tumors and renal cell carcinoma. Because the ret proto-oncogene is also inhibited by this agent, clinical evaluation of thyroid function was performed.
  
  
  OBJECTIVE
  To describe the prevalence and clinical presentation of thyroid dysfunction related to sunitinib therapy.
  
  
  METHODS
  Prospective, observational cohort study.
  
  
  METHODS
  Tertiary care hospital.
  
  
  METHODS
  42 patients treated for a median of 37 weeks (range, 10 to 167 weeks).
  
  
  METHODS
  Following analysis of serial thyroid-stimulating hormone (TSH) measurements collected prospectively during a clinical trial of sunitinib, the authors determined the proportion of patients with thyroid dysfunction.
  
  
  RESULTS
  Abnormal serum TSH concentrations were documented in 26 of 42 patients (62%): 15 (36%) developed persistent, primary hypothyroidism; 4 (10%) developed isolated TSH suppression; and 7 (17%) experienced transient, mild TSH elevations. The risk for hypothyroidism increased with the duration of sunitinib therapy. Six of 15 (40%) hypothyroid patients had suppressed TSH concentrations before developing hypothyroidism, suggesting thyroiditis. Two hypothyroid patients evaluated with thyroid ultrasonography had no visualized thyroid tissue despite normal baseline thyroid function.
  
  
  CONCLUSIONS
  The exploratory nature of this study precluded more frequent biochemical and sonographic analysis that may better define the mechanism of sunitinib-associated thyroid dysfunction.
  
  
  CONCLUSIONS
  Hypothyroidism is a frequent complication of sunitinib therapy. Regular surveillance of thyroid function is warranted in patients receiving the drug. Although the mechanism by which this complication occurs is unknown, the observations of preceding TSH suppression and subsequent absence of visualized thyroid tissue in some patients suggest that sunitinib may induce a destructive thyroiditis through follicular cell apoptosis. This provides a rationale for further investigation of sunitinib treatment in patients with advanced thyroid cancer.
authors.affiliation: Brigham and Women's Hospital, Dana Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Desai
authors.forename: Leila
authors.initials: L
authors.lastname: Yassa
authors.forename: Ellen
authors.initials: E
authors.lastname: Marqusee
authors.forename: Suzanne
authors.initials: S
authors.lastname: George
authors.forename: Mary C
authors.initials: MC
authors.lastname: Frates
authors.forename: Ming Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Morgan
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Dychter
authors.forename: P Reed
authors.initials: PR
authors.lastname: Larsen
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.forename: Erik K
authors.initials: EK
authors.lastname: Alexander
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000090063:Proto-Oncogene Mas; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D000077210:Sunitinib; D013966:Thyroiditis / Q000139:chemically induced; D013972:Thyrotropin / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011758:Pyrroles; D013972:Thyrotropin; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib