Serum metabolomic analysis in patients with Hashimoto's thyroiditis positive for TgAb or TPOAb: a preliminary study

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder, yet the metabolic abnormalities associated with HT and their relationship to antibody positivity remain poorly understood. This study aimed to characterize the distinct metabolic profiles associated with thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) positivity in female patients with HT. Serum metabolomic analysis was performed on 14 TPOAb-positive patients, 4 TgAb-positive patients, and 14 sex-matched healthy controls, evaluating a total of 225 metabolites. Partial least squares discriminant analysis (PLS-DA) revealed significant metabolic differences among the groups, identifying 36 key metabolites. Of these, 13 metabolites showed significant differences between the TPOAb-positive group and healthy controls, while 23 metabolites exhibited marked differences between the TgAb-positive group and controls. Further correlation analysis revealed a moderate positive association between TgAb and phenylacetyl-L-glutamine, while TPOAb was strongly correlated with LPC 16:0 sn-1. Additionally, metabolic pathway analysis showed significant activation of glycine, serine, and threonine metabolism in the TPOAb-positive group, whereas the TgAb-positive group exhibited enhanced activity in galactose metabolism. These findings suggest that TPOAb and TgAb positivity are associated with distinct metabolic profiles, reflecting their differential roles in metabolic pathways linked to Hashimoto's thyroiditis. This study provides valuable exploratory evidence of metabolic abnormalities in HT under different antibody-positive states, laying the foundation for future large-scale investigations to elucidate the underlying mechanisms.