Hypothyroidism after Sunitinib Treatment for Patients with Gastrointestinal Stromal Tumors

Abstract

Hypothyroidism is a frequent complication of sunitinib therapy. Regular surveillance of thyroid function is warranted in patients receiving the drug. Although the mechanism by which this complication occurs is unknown, the observations of preceding TSH suppression and subsequent absence of visualized thyroid tissue in some patients suggest that sunitinib may induce a destructive thyroiditis through follicular cell apoptosis. This provides a rationale for further investigation of sunitinib treatment in patients with advanced thyroid cancer.

Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition

“…Hypothyroidism is observed in more than a third of patients treated with sunitinib for GIST and metastatic renal cell carcinoma 68 , which may be due to the inhibition of rearranged during transfection (RET), leading to thyroid follicular cell apoptosis. In patients treated with bevacizumab, gastrointestinal perforation, poor wound healing and haemorrhage are probably directly related to the inhibition of vasculogenesis.…”

“…However, LVEF values were not reported. Any LV dysfunction could be exacerbated or even caused by the recently reported hypothyroidism that can occur as a result of sunitinib treatment 67,68 (BOX 2; TABLE 1). The potential role of sunitinib-induced hypertension, which can be significant, as a contributory factor to CHF also needs to be evaluated.…”

Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy

“…subclinical or overt hypothyroidism was observed in 4 of 22 patients (18%) who received sunitinib for 9 months, and in 5 of 17 patients (29%) who received sunitinib for longer than 12 months. 29 in patients treated for longer than 96 weeks, 90% developed increased levels of tsH. the mean time to development of hypothyroidism was 50 weeks.…”

“…the marked increase in tsH levels indicates a potential interference of sunitinib with thyroid hormone action at the pituitary level. 28 Desai and coauthors 29 prospectively evaluated the thyroid function tests (tFts) in a phase i/ii study of sunitinib therapy in 42 patients with imatinib resistant Gist. most patients received 50 mg sunitinib daily every 4-6 weeks, each consisting of 2-4 weeks of sunitinib fol lowed by 2 weeks of washout.…”

“…this clinical trial was the first to report the prevalence of sunitinib related hypothyroidism. 29 notably, the study was retrospective, and the study design precluded identifica tion of the prevalent mechanisms of sunitinib associated thyroid dysfunction. rini and colleagues 26 described thyroid abnormalities in a retrospective study of 66 patients with metastatic metastatic rCC or melanoma treated with interleukin 2 or iFnα (table 2).…”