Endocrine Abstracts

Objective: Oxidative stress has been implicated in the pathogenesis of hyperthyroidism, and its complications. Advanced glycation end products (AGEs), compounds derived from non-enzymatic transformation of macromolecules, are able to increase oxidative stress and promote inflammation and are increased in several oxidative stress-related disorders, including autoimmune thyroiditis. In the same diseases, the activity of paraoxonase-1 (PON-1), an anti-oxidant enzyme protecting against the oxidation of LDL and cell membranes, is decreased and it often negatively correlates with AGEs serum levels. No data are available on such oxidative stress parameters (AGEs and PON-1 activity) in Graves’ Disease (GD).

Materials and Methods: We enrolled 35 GD patients (30 females, aged 33-58 years) and 38 age-, sex- and BMI-matched healthy controls. All GD patients were hyperthyroid without any medical therapy at recruitment, while HCs were euthyroid. Exclusion criteria: autoimmune, inflammatory and infection comorbidities, diabetes, renal failure. Serum levels of AGEs and PON-1 activity were simultaneously assayed in sera from each subject. For AGE determination, fluorescence intensity of diluted serum was recorded at emission maximum (~440 nm) upon excitation at 350 nm; results were expressed in arbitrary units per gram of protein (AU/g protein). Serum PON-1 activity was quantified by UV spectrophotometry. The method is based on the conversion of the substrate paraoxon to p-nitrophenol by the serum PON-1. The increase in absorbance of the resulting p-nitrophenol was measured spectrophotometrically at a wavelength of 412 nm, PON1 activity was expressed in U/l; 1 unit is equivalent to 1 mmol/min of p-nitrophenol.

Results: Serum AGEs were significantly higher in GD patients than controls (mean value 389+47 AU/g protein; median 406 vs 295+60 AU/g protein; median 290 AU/g protein; P < 0.001), while PON-1 activity was significantly lower in GD subjects than in controls (mean value 90 + 54 U/l; median 67 U/l vs 256+131 U/l, median 192 U/l; P < 0.001). The two parameters were inversely correlated (P < 0.01), clearly indicating an imbalance between endogenous production of oxidants and antioxidants in hyperthyroid GD patients. Also, PON-1 activity was inversely related to free-T4 and free-T3 levels (P < 0.05), suggesting that hyperthyroidism negatively affects the anti-oxidant PON-1 activity.

Conclusion: Increased formation and accumulation of AGEs contribute to enhanced oxidative stress, along with a decrease in PON-1 activity in autoimmune hyperthyroidism. The two parameters may serve as useful markers for monitoring the levels of oxidative stress in this disorder.