Assessing PFAS mixture exposure and thyroid function in U.S. adolescents: insights from NHANES 2011-2012

Per- and polyfluoroalkyl substances (PFASs) are persistent endocrine-disrupting chemicals widely detected in human serum. Epidemiological studies suggest that PFAS exposure may disrupt thyroid function by interfering with hormone production, transport, and metabolism; however, findings remain inconsistent, particularly regarding sex-specific effects. This study aimed to (1) examine associations between serum PFAS mixtures and thyroid hormone levels in adolescents and (2) identify mixture patterns and explore sex-specific associations using a nationally representative dataset. We investigated the association between serum PFAS mixtures and thyroid function markers-including thyroid-stimulating hormone (TSH), thyroid hormones, and thyroglobulin-among 12- to 20-year-olds in NHANES 2011-2012. Principal component analysis (PCA) identified three factors: Factor 1 (long-chain carboxylates: PFUnA, PFDA, PFNA), Factor 2 (sulfonates: PFHxS, PFOS, MeFOSAA, and PFOA), and Factor 3 (PFHpA). Multivariable linear regression estimated associations between PFAS factors and thyroid hormone concentrations. Higher exposure to Factor 1 was significantly positively associated with free T4 in males but negatively associated with total T4 in females. PFASs may alter hormone clearance or interfere with feedback regulation. Factor 2 exposure was negatively associated with total T4 and positively associated with TSH in males, with statistical significance. Greater exposure to Factor 3 was significantly associated with increased total T4 in males. Overall, exposure to Factors 1 and 2 was predominantly linked to lower thyroid hormone levels, whereas Factor 3 was positively associated with thyroid hormones. These findings highlight the importance of evaluating PFAS mixtures rather than individual compounds and suggest sex-specific thyroid hormone disruptions.