Unraveling the relationship between thyroid peroxidase antibodies and thyroid hormones: A partial correlation approach in autoimmune thyroid disease

Introduction: Autoimmune thyroid disease (AITD) is a T-cell mediated disorder characterized by the presence of thyroid autoantibodies, particularly thyroid peroxidase antibodies (TPO-Ab), which serve as specific biomarkers of thyroid autoimmunity. The relationship between TPO-Ab and thyroid hormones is influenced by several confounding factors, potentially leading to inconsistent findings across studies. Methods: This cross-sectional study investigated 47 patients with AITD (35 women, 12 men; mean age 40 years) receiving levothyroxine (LT4) therapy, all with serum TPO-Ab ≥16 IU/mL. Anthropometric, glycemic, and lipid indices were measured alongside thyroid function tests, and correlations were assessed using zero-order and partial correlation analyses. Results: A significant positive correlation was found between TPO-Ab and thyroid-stimulating hormone (TSH) (r = 0.510, p < 0.001). Adjusting for age, body mass index (BMI), fasting glucose, HbA1c, and LDL-c reduced this correlation, while controlling for triglycerides (TG) and HDL-c increased it. Similar trends were observed between TPO-Ab and free thyroid hormones. Multivariate regression showed that 29.1 % of TPO-Ab variability was explained by the tested covariates, highlighting the interplay between metabolic and immunological factors. The influence of lipid parameters suggests that lipid metabolism may directly modulate autoimmunity and thyroid function. Moreover, the use of exogenous LT4, known to lower TG and HDL-c, further complicates the interpretation of antibody-hormone interactions. Conclusion: In conclusion, applying partial correlation analysis provides a more accurate assessment of the link between TPO-Ab and thyroid hormones compared to simple correlations, and supports the need for controlling metabolic and demographic covariates in both clinical practice and research to avoid misleading associations in autoimmune thyroid disease.