Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity.
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.


METHODS
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.


RESULTS
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.
Wong
Elaine
E
Endocrinology and Diabetes Division, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California, USA.
Rosen
Lee S
LS
Mulay
Marilyn
M
Vanvugt
Andy
A
Dinolfo
Melissa
M
Tomoda
Chisato
C
Sugawara
Masahiro
M
Hershman
Jerome M
JM
D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D007211:Indoles / Q000009:adverse effects*; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000009:adverse effects*; D012189:Retrospective Studies; D000077210:Sunitinib; D013960:Thyroid Function Tests
D007211:Indoles; D011758:Pyrroles; D007453:Iodide Peroxidase; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib