Current perspective on the pathogenesis, predictive features and treatment of Graves’ disease

Graves’ disease is the most common cause of hyperthyroidism in iodine-sufficient areas. Recognized that the ultimate cause of the disease is the production of autoantibodies directed to TSH-receptor, a great deal remains to be discovered on its pathogenesis. Nonetheless, due to the high risk of relapse, the identification of tailored treatment strategy, contemplating both the severity of the disease and the risk of relapse, is mandatory. Answering these queries, we firstly performed an observational, longitudinal study, involving the University of Pavia, to evaluate the current clinical features of newly diagnosed Graves’ disease patients. An innovative score (Clinical Severity Score) to assess the overall disease severity was developed by grading each component of the Merseburg triad. The predictivity of this score for the risk of persistence/relapsing of the disease was studied. Meantime, comparing newly diagnosed Graves’ disease patients to controls we speculated on a possible role of micronutrients (selenium and vitamin D) into disease pathogenesis and severity. More into-depht approaches on the role of natural killer cells and regulatory T cells in the pathogenesis of the disease were then used. Finally, we developed a randomized clinical trial to test whether the association of the supplementation with vitamin D and selenium to the standard therapy with thionamide would provide a more efficient treatment strategy. The protocol has been regularly registered (EUDRACT number 2017-00505011) and approved by the local Ethical Committee and by Agenzia Italiana del Farmaco (AIFA).