Thyrotoxicosis during sunitinib treatment for renal cell carcinoma

Context Sunitinib malate is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumours. Hypothyroidism has been observed in patients treated with sunitinib, but the mechanism whereby sunitinib induces hypothyroidism is unknown. Objective To describe a series of six patients who developed thyrotoxicosis while on sunitinib for metastatic RCC. Setting The study was conducted at Austin Health, a tertiary teaching hospital in Melbourne, Australia. Results Two patients developed severe thyrotoxicosis within 10 weeks after commencing sunitinib. In contrast, in the four patients who presented with later onset (16-30 weeks) thyrotoxicosis, the thyrotoxicosis was relatively mild, self-limiting and rapidly progressed to hypothyroidism. These patients experienced recurrent episodes of thyrotoxicosis in temporal relation to their cyclical sunitinib treatment. One patient had cytological evidence of lymphocytic thyroiditis. Conclusions These findings suggest that sunitinib-induced hypothyroidism may be a consequence of preceding thyroiditis with associated transient thyrotoxicosis. As predictive factors are currently unknown, we suggest regular monitoring of thyroid function in all patients commenced on sunitinib. Clinicians treating patients with sunitinib or other similar kinase inhibitors should to be alerted to thyroid dysfunction as a potential toxicity of these agents.