Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib

Abstract

Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted.

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

“…tFt abnormalities were detected early (the median time of detection was at cycle 2). 26 among patients with abnormal tFts, signs and symp toms related to hypothyroidism were found in 47 patients (84%). these symptoms included fatigue, cold intoler ance, anorexia, periorbital edema, fluid retention, and alterations in skin or hair.…”

“…The majority of hypothyroid patients with TKi-related hypothyroidism, pretreated with cytokines 26 or imatinib 29 ; in first-line trial of sunitinib vs interferon-α, 49 sorafenib vs placebo 50 and combination of sorafenib with interferon-α, 51 57,58 No specific data Dose dependent thyroid capillary regression; TsH was 19-fold higher than in the control group. Most of the capillaries re-grew within 2 weeks after treatment withdrawn (reversible process) 58 Imatinib increase of the nondeiodination clearance (induction of hepatic microsomal enzymes) 25 increased requirement of levothyroxine No specific data Abbreviations: reT, rearranged during transfection; TK, tyrosine kinase; TKi, tyrosine kinase inhibitor; TsH, thyroid stimulating hormone; veGFr, vascular endothelial growth factor receptor.…”

“…the most plausible are destructive thyroiditis, 29 the reduced syn thesis of thyroid hormones related to inhibition of thyroid peroxidase activity, 27 the drug induced regression of the gland vascular bed with significant capillary alteration and reduction in density. 26 the role of veGF in thyroid signaling is uncertain. 40,41 unlike treatment with antiangiogenic tKis, bevacizumab is not associated with altered thyroid homeostasis.…”

“…in total, 2 of 56 patients with rCC and a history of well controlled hypothyroidism, and 7 of 21 patients with imatinib resistant Gist, had a worsening hypothyroidism during sunitinib treatment. 26,27 De Groot et al 28 reported the case of a woman with Gist who was resistant to imatinib and received lt4 rx after thyroidec tomy and 131 i ablation for follicular thyroid carci noma. the patient's dose of lt4 rx needed to be increased after sunitinib treatment.…”

“…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). the antiangiogenic agents thalido mide 18,19 and lenalidomide 20 can cause hypothyroidism, possibly through an immune mediated subacute destruc tive thyroiditis.…”