title: Inappropriate elevation of serum thyrotropin levels in patients treated with axitinib.
abstract: BACKGROUND
  Although anticancer treatment with the tyrosine kinase inhibitor (TKI) axitinib frequently causes thyroid dysfunction, the associated mechanism and clinical features have not been elucidated.
  
  
  METHODS
  Six patients were treated with axitinib for metastatic renal cell carcinoma at the Hamamatsu University School of Medicine between 2008 and 2010. We reviewed their thyroid function results and compared them to those of patients treated with two other TKIs, sunitinib or sorafenib, and to those of subjects with normal hypothalamic-pituitary-thyroid (HPT) function.
  
  
  RESULTS
  Axitinib-induced thyroid dysfunction was observed in all patients, and two patterns were observed: increased serum thyrotropin (TSH) levels within one month after administration occurred in five patients and transient thyrotoxicosis due to destructive thyroiditis occurred in five patients within 7 months of treatment. Four patients exhibited both. When the relationship between the serum TSH and thyroid hormones was evaluated using plots of TSH versus both free thyroxine and free triiodothyronine, four patients showed an inappropriate elevation of serum TSH during administration of axitinib. Their values apparently shifted against the regression line compared to data from patients with a normal HPT function. A similar tendency, though weaker, was observed in some patients treated with sunitinib or sorafenib.
  
  
  CONCLUSIONS
  This is the first study to report an inappropriate elevation of serum TSH levels in patients treated with axitinib.
authors.affiliation: Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. kenji26@hama-med.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohba
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takayama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Matsunaga
authors.forename: Akio
authors.initials: A
authors.lastname: Matsushita
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oki
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D007191:Indazoles / Q000009:adverse effects* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013960:Thyroid Function Tests; D013966:Thyroiditis / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D013971:Thyrotoxicosis / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D013972:Thyrotropin / Q000097:blood*
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D013972:Thyrotropin; D000077784:Axitinib