Pertechnetate Thyroid Scan and Thyroid Function Tests in a Case of Sorafenib Induced Thyroiditis

摘要

Purpose of report:Sorafenib is a tyrosine kinase inhibitor used for treatment of advanced metastatic renal cell carcinoma and in recent years, for patients suffering from hepatocellular carcinoma (HCC) with limited options. Thyroiditis is a relatively rare side effect and we present one such case.Materials and Methods:We describe a 65 year old male undergoing Sorafenib treatment for advanced HCC, who developed thyroid abnormalities clinically and biochemically. Thyroid Function Tests followed over 6 months and a Tc-99m Pertechnetate scan were performed for diagnosis and evaluation.Results:The temporal connection between onset of clinical and biochemical hyperthyroidism with commencement of Sorafenib therapy in a patient with no history of thyroid disease aroused suspicions for a drug induced reaction. Follow-up over 6 months using TFTs and the thyroid scan confirms a thyroiditis with subclinical hypothyroidism that was preceded by a hyperthyroid phase.Conclusion:Correlation between TFTs and thyroid scans are useful in patients on Sorafenib therapy especially if there are clinical signs or if patients have risk factors of advanced age, prior thyroid disease or neck irradiation. Introduction Drug induced thyroiditis is often painless with patients mainly presenting with incidental abnormal thyroid function tests or less commonly clinical hyperthyroidism or hypothyroidism. The drugs most often associated with thyroiditis are interferon-alfa, interleukin-2, amiodarone, or lithium. Here we present a case of Sorafenib induced thyroiditis in a 65 year old man with advanced Hepatocellular Carcinoma (HCC). Sorafenib is a multikinase inhibitor that has already been approved for the treatment of metastatic Renal Cell Cancer (mRCC). Sorafenib targets the Raf/mitogen-activated protein kinase/extracellular signal–related kinase (ERK) signaling pathway as well as other tyrosine kinases like vascular endothelial growth factor receptor and platelet-derived growth factor receptors which are important for tumor cell proliferation and angiogenesis. The phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) trial1 demonstrated a significant survival benefit (placebo, 7.9 months; sorafenib, 10.7 months) and good tolerance in patients with HCC, making sorafenib the new reference standard for systemic therapy of patients with advanced HCC in 2006. To date there have been 3 studies looking into thyroid abnormalities post Sorafenib treatment in mRCC. Here we describe the work-up and diagnosis of Sorafenib induced thyroiditis in this patient. Case Report A 65 year old man was diagnosed with HCC and had a right hemihepatectomy in 2006. Following that, there were a further 4 occasions where he required Transcatheter Arterial Chemo-Embolisation (TACE) for recurrence of the HCC over the period from July 2007 to December 2008. In March 2009, during a routine follow-up scan, new peritoneal deposits, a left lung lesion and persisting liver lesions were found. Due to the advanced nature of the disease and limited treatment options, Sorafenib was commenced within 2 months, from 200mg daily (1 week) to 400mg daily (1 week) and finally the full dose of 400mg BD (in the 3rd week).4 months post initiation of the systemic treatment, he developed symptoms of weight loss, loss of apetite and tremors. There was however no pain or tenderness associated with his thyroid gland. Thyroid Function Tests (TFT) were performed and showed significantly reduced Thyroid Stimulating Hormone (TSH) levels ( 31.0 pmol/ml) and T4 ( > 155 pmol/ml) levels. These levels and his symptoms indicated overt hyperthyroidism; with no previous history of thyroid problems. In addition, the Thyroglobulin (TG) level ( 2292 pmol/ml) and Thyroid Peroxidase Antibody (TPO-Ab) level ( 128 Iu/ml) were both significantly raised. The Sorafenib treatment was ceased and carbimazole and propanalol given until his symptoms resolved after which the patient was re-commenced on Sorafenib again with close mo