Biochemical Remodeling of Purine Metabolism and Lipid Peroxidation Across Thyroid Disease Phenotypes

Background and Objectives: Purine-metabolism profiles across distinct thyroid phenotypes remain poorly characterized despite the recognized redox imbalance associated with thyroid dysfunction and autoimmune thyroiditis (AIT). We compared plasma and erythrocyte purine-metabolite profiles, derived purine ratios, and their associations with lipid peroxidation across four thyroid-disease phenotypes and healthy controls. Materials and Methods: This single-center cross-sectional study included 164 participants: hypothyroidism without AIT (n = 31), AIT with hypothyroidism (n = 30), nontoxic nodular goiter with euthyroidism (n = 42), euthyroid AIT (n = 37), and healthy controls (n = 24). Purine metabolites were assessed by direct UV spectrophotometry and expressed in relative extinction units; thiobarbituric acid-reactive substances (TBARS)-derived malondialdehyde (MDA) equivalents were measured in plasma and erythrocytes. Results: Plasma guanine and hypoxanthine were lower in AIT with hypothyroidism than in hypothyroidism without AIT and in euthyroid AIT than in nontoxic nodular goiter. Plasma X/HX and UA/HX were higher in both AIT groups than in controls. Plasma MDA was elevated in all thyroid-disease groups, whereas erythrocyte MDA was highest in hypothyroidism without AIT. Plasma UA/X correlated positively with both plasma and erythrocyte MDA, and plasma UA/HX with plasma MDA, with phenotype-dependent heterogeneity in stratified analyses. Conclusions: Thyroid phenotypes showed distinct compartment-specific purine and lipid-peroxidation patterns rather than a uniform AIT-dependent shift. Purine ratios should be interpreted as indirect, method-specific indices rather than direct measures of metabolic flux or XOR/XO/XDH activity.