Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis

Background: Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)compounds formed by the transformation of proteinswere evaluated as potential new markers of oxidative stress in this disease. Methods: This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; M-age=3813 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. Results: Serum d-ROMs were elevated, and BAP decreased in HT patients compared with controls (p<0.001), and the two parameters were inversely correlated (r=-0.211; p=0.027), clearly indicating an enhanced oxidative stress. Furthermore, AGE levels were higher in HT patients (M=223.18 AU/g prot) than in controls (M=189.636 AU/g prot; p=0.020) and inversely correlated with BAP levels (r=-0.196; p=0.037). In uni- and multivariate analysis, serum antithyroperoxidase antibodies were the main predictors for d-ROMs (p=0.006), BAP (p<0.001), and AGEs (p=0.014), irrespective of thyrotropin and/or free thyroxine values. No differences in AOPPs levels were found between patients and controls (p=0.923). Conclusions: Oxidants are increased and antioxidants decreased in euthyroid HT patients. As a result, the oxidative/antioxidative balance is shifted toward the oxidative side. Moreover, this study reports on a possible significant involvement of AGEs in HT, thus contributing to a better definition of the redox homoeostasis dysregulation in HT.