Association between per- and polyfluoroalkyl substance exposures and thyroid homeostasis parameters

Abstract Context Prevailing studies have shown the disruption effect of per- and polyfluoroalkyl substances (PFAS) on thyroid homeostasis. However, most studies focused on individual thyroid hormones. Objective To explore the associations between PFAS exposures and thyroid homeostasis parameters. Methods A total of 2386 adults from NHANES (2007-2008 and 2011-2012) were included. Thyroid homeostasis parameters included central and peripheral thyroid hormone sensitivity, calculated by thyroid hormones. Multivariable survey-weighted linear regressions were performed to determine the association between PFAS exposure and thyroid homeostasis parameters. The weighted quantile sum (WQS) and the quantile g-computation (QGC) models were used to estimate the mixed effects of co-exposures to PFAS. Results The ratio of free triiodothyronine/free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD) were positively associated with perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid, perfluorononanoic acid and perfluorohexane sulfonic acid, respectively. However, no significant associations were observed between PFAS exposure and central thyroid sensitivity parameters. PFAS co-exposures was positively associated with FT3/FT4 (β = 0.013, P < 0.001) and SPINA-GD (β = 1.230, P < 0.001) in WQS models. Consistently, PFAS concentrations per quantile was linked to an increase in FT3/FT4 (β = 0.004, P = 0.002) and SPINA-GD (β = 0.392, P = 0.008) in GQC models, with PFOA having the highest weight in all models. Conclusion This study revealed that PFAS exposures may affect peripheral thyroid hormone sensitivity instead of central among U.S. general adults, enhancing our understanding of the correlation between PFAS exposure and thyroid hormones and providing insights into potential health implications.