ISSN 1849-9031 (Online)

ISSN 1849-8922    (Print)

Tyrosine kinase inhibitors and hypothyroidism – an intriguing link.
Davor Kust, Marin Prpić, Ivan Kruljac, Ante Bolanča, Zvonko Kusić.


Purpose: Along with increased cancer incidence, there is also an increased use of targeted cancer therapy. One of the most potent classes of targeted therapy drugs are tyrosine kinase inhibitors (TKIs). Several new TKIs have become available in clinical practice after the correlation of sunitinib and hypothyroidism was documented. The aim of this review is to assess all relevant studies regarding clinically approved TKIs, in respect to hypothyroidism as a side-effect, and to investigate the possible predictive value of hypothyroidism in patients taking these drugs.

Methods: Drugs that are approved by the United States Food and Drug Administration (FDA) for clinical use are evaluated in this study. In order to identify studies regarding hypothyroidism as a side-effect of TKIs, a systematic PubMed/Medline literature search was conducted.

Results: Currently, the FDA has approved 26 different TKIs for use in clinical practice. The total number of yielded PubMed/Medline results was 232. Conclusions: Sunitnib, sorafenib, imatinib, pazopanib, and axitinib are TKIs with a definitive link to hypothyroidism. According to some current studies, patients who develop hypothyroidism during TKI therapy have prolonged progression-free survival. Despite the fact that hypothyroidism is nowadays a well known side-effect of therapy with many different TKIs, there are still no established guidelines for its treatment. Further studies in this area are needed, especially for lesser investigated drugs. It would be prudent to consider routine monitoring of thyroid function in all patients who receive TKIs, and to recommend endocrinological consultation as necessary.