| Summary: | Perfluoroalkyl acids (PFAS) are known endocrine disrupting chemicals, potentially affecting thyroid function. Smoking has been associated with PFAS levels as well as with thyroid function. The impact of smoking on the association between PFAS and thyroid function remains to be elucidated, so the objective was to assess the effect of PFAS exposure on thyroid function in the general population, stratified by smoking status, using the National Health and Nutrition Examination Survey (NHANES). NHANES adult participants who were part of the 2011–2012 laboratory subsample and had PFAS and thyroid function measured were included (<i>n</i> = 1325). Adjusted linear regression models and stratified analyses were performed. There was a significant positive association between perfluorooctanesulfonic acid (PFOS) (<i>p</i> = 0.003), perfluorononanoic acid (PFNA) (<i>p</i> = 0.014), total PFAS (<i>p</i> = 0.004) concentrations and free T4 (FT4). No significant associations were found between perfluorooctanoic acid (PFOA), PFOS, perfluorohexane sulfonate (PFHxS), PFNA, total PFAS and total T4 (TT4) or thyroid stimulating hormone (TSH). In non-smokers, a significant positive association was found between PFOS (<i>p</i> = 0.003), PFHxS (<i>p</i> = 0.034), PFNA (<i>p</i> = 0.012), total PFAS (<i>p</i> = 0.003) and FT4 while no significant associations were found in smokers. The present study showed that increased PFAS exposure was associated with increased FT4 in non-smokers, while no association was found in smokers. These results confirm that smoking modifies the association between PFAS exposure and thyroid function.
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