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Endocrine Abstracts (2010) 21 P404

1Diabetes and Endocrinology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 2Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK.


Sunitinib, a tyrosine kinase inhibitor, inhibits VEGF-mediated tumour angiogenesis. Following NICE approval, it is increasingly used in the treatment of metastatic renal cell carcinoma.

Hypothyroidism in sunitinib-treated individuals was first described in 2005. The aetiology remains uncertain and possibly reflects a destructive thyroiditis. Incidence rates of hypothyroidism from case series vary between 36 and 85%. We report a retrospective analysis of thyroid-function in patients treated with sunitinib for metastatic renal cell carcinoma at a UK tertiary hospital.

Twenty-six patients (18 men, 8 women; median age 62.5 years (range 32–80)) were started on sunitinib between September 2007 and April 2009. All patients received sunitinib for more than three cycles (25–50 mg/day; 4-weeks-on and 2-weeks-off per cycle). Sixteen patients (61%) had baseline thyroid function tests (mean TSH 2.44 (S.D.+2.45) mIU/l, NR 0.27–4.20 mIU/l; mean FT4 16.23(S.D.+2.62) pmol/l, NR 12–22 pmol/l). Pre-treatment TSH was elevated in two patients (4.61 and 10.7 mIU/l) increasing to 47.4 and 42.1 mIU/l respectively, after one cycle. At the first follow-up thyroid assessment, which was done between the 1st and 8th cycle (median 3 cycles), the mean TSH was 5.0 (S.D.+8.09) mIU/l (ΔTSH 2.56, 95%CI 1.76–6.78). Free-T4 was normal with a mean value 15.86 (s.d.+1.80) pmol/l. One patient had a thyrotoxic phase before progressing to hypothyroidism. Median time-point for the 2nd follow-up was after 4 cycles (range 3–12) and the third follow-up occurred after 6 cycles (range 3–13). Thirteen patients (50%) had a high TSH (median 11.4 mIU/l (range 5.48–80) during follow-up and 8 (30%) were started on levothyroxine due to a progressive increase in TSH.

In conclusion, hypothyroidism is a common complication of Sunitinib therapy and may adversely affect tolerance. Local protocols for thyroid surveillance and thyroxine replacement will enhance recognition and enable early treatment of this unusual clinical entity.

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