title: Tyrosine kinase inhibitor-induced thyroid disorders: a review and hypothesis.
abstract: BACKGROUND
  Thyroid dysfunction is a well-known adverse effect of sunitinib, a drug that targets multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR). As several kinds of tyrosine kinase inhibitors (TKIs) are now available, this has been postulated to be a side effect of the TKIs that target the VEGFR (VEGF-TKIs). However, sunitinib, one of the first-generation TKIs, likely causes thyroid dysfunction more frequently than other TKI classes, leading not only to hypothyroidism, but also to thyrotoxicosis.
  
  
  CONCLUSIONS
  Based on the reports published to date, including our own studies, we have hypothesized that sunitinib may exert these effects, because it targets a broad spectrum of tyrosine kinases. This not only includes VEGFR2, but also VEGFR1 and the platelet-derived growth factor receptor (PDGFR). This, in turn, may suggest that not only VEGFR2 but also the PDGFR and/or the VEGFR1 play an important role during angiogenesis in the thyroid.
  
  
  CONCLUSIONS
  Our current hypothesis may explain the mechanisms that underlie TKI-induced thyroid disorders. By learning how various kinds of TKIs affect thyroid function, we may elucidate how the angiogenesis in thyroid is regulated both physiologically and pathologically.
authors: Department of Endocrinology and Nephrology, School of Medicine, University of Tokyo, Tokyo, Japan. norimaki-tky@umin.ac.jp
authors: Noriko
authors: N
authors: Makita
authors: Taroh
authors: T
authors: Iiri
mesh_terms: D006801:Humans; D007037:Hypothyroidism; D007211:Indoles / Q000009:adverse effects*; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D000077210:Sunitinib; D013959:Thyroid Diseases / Q000139:chemically induced*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib