Sunitinib Induces Hypothyroidism in Advanced Cancer Patients and May Inhibit Thyroid Peroxidase Activity
Abstract
OBJECTIVE: Sunitinib is a novel tyrosine kinase inhibitor with antitumor and antiangiogenic effects. An observed higher than expected rate of hypothyroidism in sunitinib-treated patients prompted assessment of the incidence of hypothyroidism. DESIGN: Patients taking sunitinib had their thyroid function tests (TFTs) assessed via chart review. To explore potential effects on the thyroid, we examined the antiperoxidase activity of sunitinib by in vitro testing its effect on guaiacol oxidation and protein iodination by lactoperoxidase. MAIN OUTCOME: Of the 89 patients who took sunitinib, 49 patients were excluded from analysis for several reasons. Of the remaining 40 patients, 21 (53%, 24% of the original 89) developed elevated thyrotropin (TSH) after a median of 5 months (range 1-36 months). Median TSH was 21.4 mU/L (range 4.6-174 mU/L). In vitro, sunitinib had antiperoxidase activity that was about one-fourth the potency of propylthiouracil. CONCLUSIONS: Of the 40 patients who had TFTs assessed after starting sunitinib, 53% developed elevated TSH. We recommend that all patients treated with sunitinib be monitored for hypothyroidism. The mechanism of the antithyroid effect appears to be inhibition of peroxidase activity. Further research is needed to confirm the mechanism by which sunitinib induces hypothyroidism.
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Upgraded titration of L-T4 was reported in athyreotic patients prescribed imatinib, motesanib, sorafenib, sunitinib, and vandetanib.
“Upgraded titration of L-T4 was reported in athyreotic patients prescribed imatinib, motesanib, sorafenib, sunitinib, and vandetanib (5, 62, 63).”
From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [62]
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“Upgraded titration of L-T4 was reported in athyreotic patients prescribed imatinib, motesanib, sorafenib, sunitinib, and vandetanib (5, 62, 63).”
Background
- Authors
- Wong, E., Rosen, L. S., Mulay, M., VanVugt, A., Dinolfo, M., Tomoda, C., Sugawara, M., & Hershman, J. M.
- Affiliations
- VA Greater Los Angeles Healthcare System (US)
- Premiere Oncology, Los Angeles, California.
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2007-04
- Volume
- 17
- Issue
- 4
- Pages
- 351-355
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2051963942
- Cited by
- 206
- References
- 11
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 4 · 2017: 6 · 2016: 12 · 2015: 7 · 2014: 21 · 2013: 12 · 2012: 15
- FWCI
- 13.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Thyroid Association
- Pfizer
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- sunitinib, hypothyroidism, thyroid peroxidase inhibition, tyrosine kinase inhibitors, thyroid-stimulating hormone, thyroid function tests, advanced cancer, drug-induced thyroid dysfunction, propylthiouracil
- MeSH terms
- Sunitinib, Humans, Hypothyroidism, Indoles, Iodide Peroxidase, Protein-Tyrosine Kinases, Pyrroles, Retrospective Studies, Thyroid Function Tests, Gastrointestinal Stromal Tumors
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