Longitudinal PFAS exposure and thyroid function trajectories in Taiwanese youth: a 10-year prospective cohort study

BACKGROUND: Evidence linking per- and polyfluoroalkyl substances (PFAS) to thyroid dysfunction is growing, yet longitudinal data spanning adolescence to early adulthood remained limited. METHODS: We analyzed 495 participants aged 12-30 years in the YOung TAiwanese Cohort (YOTA) followed for 9-12 years. 11 Plasma PFAS and serum thyroid-stimulating hormone (TSH) and free thyroxine (free T4) were measured at baseline and follow-up. PFAS exposure index was derived as the mean of these standardized ln-PFAS concentrations. Using multivariable ANCOVA-style linear regression models, we examined associations of baseline PFAS levels and changes in PFAS with follow-up ln-TSH and ln-free T4, and incident thyroid disease was examined using Cox models. RESULTS: In multivariable models, both higher baseline PFAS exposure index and a more positive change in PFAS exposure index were associated with lower follow-up TSH (-17.22%, p = 0.003; and - 16.81%, p = 0.011, respectively). Several baseline PFAS compounds showed inverse associations with follow-up TSH, including linear PFOA, linear PFOS, N-MeFOSAA, and PFHpA; inverse associations for PFAS changes were most evident for linear PFOA and linear PFOS. For free T4, baseline PFAS measures were not significant after FDR correction, whereas a more positive change in PFAS exposure index was associated with higher follow-up free T4 (+5.55%, p = 0.001), with nominal positive associations observed for linear PFOA and PFDoA. These patterns were robust in sensitivity analyses (including baseline-only/change-only specifications, change-score models, and exclusions of baseline/follow-up thyroid dysfunction). In Cox regression analyses, greater annualized increases in the PFAS exposure index were associated with lower risks of hypothyroidism and thyroid nodules. CONCLUSIONS: PFAS exposure was associated with lower TSH and higher free T4 over 10 years of follow-up, suggesting sustained thyroid-axis perturbation from adolescence into young adulthood. These findings underscore a susceptible developmental window and support long-term biomonitoring and stronger regulatory action where PFAS contamination persists.