Opposing effects of PM2.5 on TSH levels: effect modification by thyroid peroxidase antibody status in a preconception cohort

Background: Fine particulate matter (PM2.5) is a significant source of endocrine disrupting chemicals. However, epidemiological evidence linking PM2.5 exposure to thyroid function, particularly thyroid-stimulating hormone (TSH), remains inconsistent. We hypothesized that this inconsistency stems from unmeasured effect modification by thyroid autoimmunity status, specifically the presence of thyroid peroxidase antibodies (TPOAb). Objective: To examine whether TPOAb status modifies the association between PM2.5 exposure and thyroid function in women planning pregnancy. Methods: This cohort study was conducted in Liaoning, China as a part of the China Medical University Birth Cohort. Serum TSH, FT4, and FT3 were measured, along with TPOAb and TgAb status. PM2.5 exposure was estimated for 1 to 12 month periods prior to blood draw. Linear regression with interaction terms was used to assess effect modification by TPOAb status. Results: A total of 1,357 women were included between January 2019 and December 2023. A significant interaction was observed between half-year average PM2.5 exposure and TPOAb status on TSH levels (P for interaction = 0.003). Critically, the direction of association was opposite: each 10 μg/m³ increase in PM2.5 was associated with a decrease in TSH among TPOAb-negative women (β = -0.074, 95% CI: -0.122, -0.026), but with an increase in TSH among TPOAb-positive women (β = 0.156, 95% CI: 0.014, 0.299). This effect modification was specific to TSH (no associations with FT4 or FT3), most pronounced for the 6-month exposure window. Conclusion: TPOAb status critically modifies the direction of association between PM2.5 exposure and TSH levels in preconception women. TPOAb-positive women may represent an environmentally susceptible subgroup, highlighting the importance of considering individual autoimmune status in environmental endocrine disruption research.