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Sunitinib-induced hypothyroidism is due to induction of type 3 deiodinase activity and thyroidal capillary regression

Mariëtte H W Kappers1, Joep H M van Esch, Frank M M Smedts

  • 1Division of Pharmacology, Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands. m.h.w.kappers@erasmusmc.nl

The Journal of Clinical Endocrinology and Metabolism
|August 6, 2011
PubMed
Abstract

Insights

Sunitinib cancer treatment can cause hypothyroidism by altering thyroid hormone metabolism and damaging thyroid blood vessels. These effects on thyroid function largely reversed after discontinuing sunitinib therapy.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • The tyrosine kinase inhibitor sunitinib is a common anticancer therapy.
  • Sunitinib treatment is associated with the development of thyroid dysfunction.
  • The precise mechanisms and timeline of sunitinib-induced thyroid dysfunction require elucidation.

Purpose of the Study:

  • To investigate the time course of thyroid dysfunction during sunitinib treatment.
  • To explore the underlying mechanisms of sunitinib-induced hypothyroidism.
  • To assess the reversibility of these effects after sunitinib withdrawal.

Main Methods:

  • Retrospective and prospective analysis of thyroid function tests in patients receiving sunitinib.
  • Assessment of thyroid hormones, deiodinase activity, and thyroid histology in a rat model.
  • Sunitinib administration followed by a withdrawal period in rats to evaluate reversibility.

Main Results:

  • Over 40% of patients developed elevated TSH levels within 10 weeks of sunitinib treatment.
  • A decreased T3/rT3 ratio was observed, indicating altered thyroid hormone metabolism.
  • Rats exhibited decreased T4 and T3, increased hepatic deiodinase activity, and thyroid capillary regression, which reversed upon drug withdrawal.

Conclusions:

  • Sunitinib induces hypothyroidism through mechanisms involving altered T4/T3 metabolism.
  • Thyroid capillary regression is another significant factor in sunitinib-induced thyroid dysfunction.
  • The observed thyroid dysfunction is largely reversible after cessation of sunitinib treatment.

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