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Unanswered questions regarding the management of sunitinib-induced hypothyroidism

Nature Clinical Practice Oncology volume 4, page 674 (2007)Cite this article

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Hypothyroidism seems to be a risk of sunitinib therapy for cancer. We review the evidence for the occurrence of hypothyroidism in this setting and discuss possible actions of thyroid hormone replacement in patients with cancer.

Multitargeted tyrosine kinase inhibitors are novel oral chemotherapeutic agents with efficacy in treating advanced renal cell carcinoma (RCC) and gastrointestinal stromal tumors, among others cancers. Prolonged administration of some tyrosine kinase inhibitors, such as sunitinib, however, might lead to decreased thyroid function. The common adverse event of fatigue in sunitinib-treated patients reflects drug-induced hypothyroidism in 30–40% of individuals who experience such symptoms.1,2 Sunitinib inhibits thyroid peroxidase in a similar fashion to propylthiouracil (PTU), albeit to only one-quarter the degree.3 In preclinical models, administration of various VEGF pathway inhibitors caused marked thyroid capillary fenestration and regression, with an associated rise in thyroid-stimulating hormone (TSH);4 therefore, patients with RCC and pre-existing thyroid disease might be particularly susceptible to hypothyroidism while receiving sunitinib. The normal thyroid gland contains several months' store of thyroid hormone and would explain the delay in onset of hypothyroidism seen in patients receiving sunitinib.1,2 Imatinib use in thyroidectomized cancer patients with hypothyroidism might also increase the dose of replacement thyroid hormone needed,5 suggesting that imatinib affects disposal of thyroid hormone. What is apparent is that hypothyroidism can complicate the management of solid tumors with tyrosine kinase inhibitors, and thyroid hormone replacement has been, therefore, routinely recommended in this setting.1,2

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Authors and Affiliations

  1. D Garfield is a medical oncologist affiliated with the University of Colorado Health Sciences Center, A Hercbergs is a Radiation Oncologist at the Cleveland Clinic Foundation, Cleveland, OH,

    David Garfield & Aleck Hercbergs

  2. P Davis is Senior Associate Dean for Clinical Research and Professor of Medicine at Albany Medical College, Albany, NY, USA.,

    Paul Davis

Authors
  1. David Garfield
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  2. Aleck Hercbergs
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  3. Paul Davis
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Corresponding author

Correspondence to David Garfield.

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Competing interests

DH Garfield is a consultant for the following companies: Array BioPharma, AstraZeneca and Pharmatech. The other authors declared no competing interests.

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Garfield, D., Hercbergs, A. & Davis, P. Unanswered questions regarding the management of sunitinib-induced hypothyroidism. Nat Rev Clin Oncol 4, 674 (2007). https://doi.org/10.1038/ncponc0998

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