Background: The objective of this study was to evaluate if hypothyroidism developing during sunitib therapy in patients with metastatic renal cell carcinoma (mRCC) is associated with a better outcome. Methods: Thirty-one consecutive patients with clear cell mRCC were retrospectively analyzed. Thyroid function was assessed prior to therapy, every 6 weeks during the first 6 months and every 2–4 months thereafter. Hypothyroidism was considered present if thyroid-stimulating hormone (TSH) exceeded the upper normal limit (UNL) with normal triiodothyronine (T3) and thyroxine (T4). Results: Hypothyroidism occurred in 16 patients (52%) within 3 months (range 0.7–22.9) of treatment initiation. Thyroid replacement corrected TSH below the UNL in 10 patients (63%). The distribution according to Motzer prognostic criteria revealed good prognosis in 16 patients (52%), intermediate in 9 (29%) and poor in 6 (19%). The hypothyroid patients tended to have longer progression-free survival (PFS; median 12.2 vs. 9.4 months; p = 0.234) and longer survival (median 22.4 vs. 13.9 months; p = 0.234) than the euthyroid patients. Clinical benefits were similar in both groups. Conclusions: Hypothyroidism that develops in mRCC patients treated with sunitinib is associated with a trend toward prolonged PFS and survival, with a similar clinical benefit rate.

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