Effect of sunitinib on growth and function of FRTL-5 thyroid cells

Thyroid. 2008 Jun;18(6):631-5. doi: 10.1089/thy.2007.0336.


Background: Sunitinib, a multitargeted vascular endothelial growth factor and receptor tyrosine kinase inhibitor, causes hypothyroidism in patients who take it for treatment of cancer. Although the pathophysiologic mechanism of the hypothyroidism is unclear, it has been claimed that it is due to inhibition of iodide uptake.

Methods: To evaluate the pathologic mechanism of induction of the hypothyroidism, we studied the effect of sunitinib on FRTL-5 rat thyroid cells. We measured the effect of sunitinib on cell growth, (125)I-iodide uptake and efflux, TSH receptor (TSH-R), and sodium-iodide symporter (NIS) message.

Results: At 48 hours, sunitinib caused a dose-related inhibition of growth with LC(50) of 14.6 muM, but there was no apparent inhibition of growth at 24 hours at concentrations of 0.1-25 microM. Preincubation with sunitinib did not impair the response to TSH, indicating that it did not affect the TSH-R. Incubation with sunitinib for 24 hours caused a dose-related increase of (125)I-iodide uptake and did not reduce iodide efflux or NIS mRNA expression.

Conclusion: The data indicate that sunitinib is unlikely to cause hypothyroidism by inhibition of iodide uptake.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Biological Transport / drug effects
  • Cell Line
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology*
  • Iodine Radioisotopes / pharmacokinetics
  • Pyrroles / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Thyrotropin / drug effects
  • Receptors, Thyrotropin / metabolism
  • Sunitinib
  • Symporters / metabolism
  • Thyroid Gland / cytology
  • Thyroid Gland / drug effects
  • Thyroid Gland / growth & development*
  • Thyroid Gland / metabolism
  • Time Factors


  • Angiogenesis Inhibitors
  • Indoles
  • Iodine Radioisotopes
  • Pyrroles
  • RNA, Messenger
  • Receptors, Thyrotropin
  • Symporters
  • sodium-iodide symporter
  • Sunitinib