Background: Sunitinib (SUN) is a novel oral multitarget tyrosine-kinase inhibitor (TKI) that has demonstrated its efficacy in the treatment of metastatic renal cell carcinoma (mRCC). The thyroid dysfunction is one of the most common side effects of SUN. The mechanisms inducing thyroid dysfunction are still poorly understood.
Aim: Identify the incidence, severity, ultrasonographic changes and pattern of response of thyroid function tests during treatment with SUN.
Methods: This ongoing prospective observational study to date has completed the evaluation of 25 mRCC patients: ten women (59±18 years) and 15 men (65.5±7 years). 5/25 patients received LT4 replacement therapy and 11/25 had thyroid nodules at enrollment. SUN was administered at daily dose of 50 mg (schedule 4/2). Thyroid function tests were assessed at baseline and at week-4 and -6 of each cycle, ultrasound at baseline and after the first and the third SUN cycle.
Results: we observed an increase in TSH values, most frequently after the second cycle of SUN (mean-TSH 17.05±43.56 μUI/ml) and in older men (mean-TSH 91.95±106.4 μUI/ml. TSH rose above normal range (0.354.94 μUI/ml) only in patients which were not on LT4 replacement at enrollment. Half of untreated patients had an TSH elevation requiring LT4 replacement after the first cycle; all of them required a further dosage increase after the second cycle. No dose-adjustment was needed in patients already on LT4 at enrollment. In all patients, a volumetric reduction of thyroid lobes occurred at week-6. Ultrasound at week-18, detected the appearance of a hypoechoic solid nodule in one patient and a volumetric increase of pre-existing nodules in two other patients.
Conclusion: SUN is associated with thyroid functional and morphological changes occurring rapidly, within few weeks, in most but not all patients. Distinct individual patterns of response to TKI are identified allowing a better prognosis and management.