Clinical and molecular studies on differentiated thyroid carcinoma management

Abstract

This thesis describes clinical and fundamental studies addressing clinical challenges in patients with differentiated thyroid carcinoma (DTC). The diagnosis of DTC is hampered by the fact that although the incidence is low thyroid nodules are prevalent. In this thesis, the diagnostic value of a potential marker for DTC has been studied. Unfortunately, in a high proportion of patients with metastases of DTC, the tumor has become resistant to RAI therapy. We have performed fundamental studies into the mechanisms of the regulation of the sodium iodide symporter (NIS) that may have implications for restoring susceptibility to RAI therapy. Furthermore, the long-term efficacy of a new treatment with the multi kinase inhibitor (MKI) sorafenib for DTC patients with metastases that are unresponsive to RAI has been evaluated. Therapy with MKI has numerous adverse effects, including hypothyroidism. We have evaluated a potential mechanism of sorafenib associated hypothyroidism. Finally, DTC patients have traditionally been treated with TSH suppressive levothyroxine substitution. However, high thyroid hormone concentrations may have adverse effects on various organ systems, including the heart. In this thesis, we studied the effects of various thyroid hormone concentrations on cardiac function in DTC, using dedicated cardiac ultrasound.