Clinical Endocrinology (2008) 69 , 669–672 doi: 10.1111/j.1365-2265.2008.03253.x © 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd 669 O R I G I N A L A R T I C L E Blackwell Publishing Ltd Thyrotoxicosis during sunitinib treatment for renal cell carcinoma Mathis Grossmann*, Erosha Premaratne*, Jayesh Desai† and Ian D. Davis‡ * Endocrine Unit, Austin Health, Victoria, Australia; †Oncology Unit, Royal Melbourne Hospital, Victoria, Australia; and ‡ Ludwig Oncology Unit, Austin Health, Victoria, Australia Summary 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 aftercommencing 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 pro- gressed 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. (Received 7 November 2007; returned for revision 6 December 2007; finally revised 1 February 2008; accepted 25 March 2008) Introduction Sunitinib malate is an oral tyrosine kinase inhibitor approved for in the treatment of renal cell carcinoma (RCC) and gastrointestin stromal tumours (GIST). 1 In the first published series of 42 gastro- intestinal stromal tumour patients treated with sunitinib, 36% de persistent primary hypothyroidism after a median of 37 wee sunitinib therapy. 2 Hypothyroidism was also reported in RCC at rates of up to 85% 3–5 but sunitinib-induced thyrotoxicosis has not been previously described. Here we report six patients who developed thyrotoxicosis whil on sunitinib, presumably as a consequence of sunitinib-induced thyroiditis. The clinical course of two patients with severe thyrot is presented in detail. Patients and methods In 2005–06, 31 patients with metastatic RCC received sunitinib therapy at the Austin Health Cancer Centre. Routine measureme of thyroid function tests (TFTs) were performed from mid 2006 a reports of sunitinib-induced hypothyroidism became available. 2–5 Of the 25 patients in whom TFTs were measured, 12 (48%) develop thyroid dysfunction. Of these, two had a transiently reduced TSH with normal fT4 and fT3, four developed hypothyroidism without evidence of preceding hyperthyroidism and six developed hyper roidism (Table 1). Ultimately, eight of the 25 subjects (32%) dev permanent hypothyroidism. Of the six patients with hyperth roidism (Table 1), four patients received sunitinib in the context a clinical trial (clinicaltrials.gov identifier: NCT00130897). The ot two patients received sunitinib as part of a compassionate use a scheme. Sunitinib was commenced at 50 mg/day for 28 days for 6-week cycle, as per usual practice. The protocol was approved the Austin Health Human Research Ethics Committee and all tria patients provided written consent. Patient characteristics Of the six patients who developed thyrotoxicosis, four were male two female with age ranges of 38–64 years (Table 1). Patient 2 h a past history of Graves’ disease. None of the other five patients a personal or family history of thyroid disease and none had clin evidence of a goitre, nodular thyroid disease or Graves’ disease. This work has previously been presented in part at the Medical Oncology Group of Australia, the Clinical Oncological Society of Australia and the Endocrine Society of Australia annual scientific meetings. Correspondence: Ian D. Davis, Ludwig-Austin Joint Medical Oncology Unit, Austin Hospital, Studley Rd, Heidelberg, Victoria 3084, Australia. Tel.: +61 39496 5726; Fax: +61 39457 6698; E-mail: ian.davis@ludwig.edu.au