Endocrine Abstracts

Introduction: TKI are an emerging group of anti-growth factor agents used in the treatment of solid cancers. Treatment is associated with thyroid dysfunction. Sunitinib is licensed for the treatment of metastatic RCC. Our objective was to determine the incidence of Sunitinib induced thyroid dysfunction and its management in patients with renal RCC.

Methods: Retrospective case note analysis of patients started on Sunitinib for metastatic RCC between January 2010 and December 2012 at the Oncology Unit in JCUH.

Results: 31 patients were started on Sunitinib between 2010 and 2012.One patient had pre-existing primary hypothyroidism and was excluded from analysis. Baseline TFTs were done in 93% of patients. The majority of patients (n=26) were euthyroid pre-treatment; at baseline, three patients (10%) had subclinical hypothyroidism and one patient (3.3%) had subclinical hyperthyroidism. Mean duration of follow-up was 53.33 weeks. Mean interval between starting Sunitinib and 1st TFT check – 3.3 weeks (range 2–12 weeks, s.d. 2.28). Mean interval to developing abnormal TSH was 9.3 weeks (range 2–42 weeks, s.d. 11.58). Primary hypothyroidism in this cohort developed at 27.7 weeks (range 4–46 weeks). The mean time to commencing levothyroxine (LT₄) therapy was 55.5 weeks (range 21–105 weeks). Sunitinib induced hypothyroidism developed in six patients (20%) whilst subclinical hypothyroidism developed in two patients (6.6%). 21 patients (70%) were biochemically euthyroid. Thyroid status of one patient with baseline subclinical hyperthyroidism remained unchanged. Four patients (13.3%) developed transient subclinical hypothyroidism. Mean TSH level at the start of LT₄ therapy was 55.7 mIU/l (range 19.43–107.24) and mean free T₄ was 8.4 pmol/l (range 3.5–11.8). LT₄ was commenced at a mean dose of 39 μg OD (range 25–50 μg) and the average final dose was 118 μg OD (range 50–225 μg).

Conclusion: Primary hypothyroidism is a common adverse effect of TKI therapy. The incidence in this cohort (20%) was similar to hypothyroidism rates in published data from Sunitinib studies (14–46%). There appeared to be a significant delay between the diagnosis of overt primary hypothyroidism and the start of LT₄. Regular pre-cycle TFT checks and close liaison with Endocrinology team will help reduce morbidity from delayed diagnosis and treatment of hypothyroidism.