Sex-specific effect of urinary metabolites of polycyclic aromatic hydrocarbons on thyroid profiles: Results from NHANES 2011-2012
Authors: Xing Weilong , Gu Wen , Liang Mengyuan , Wang Zhen , Fan Deling , Zhang Bing , Wang Lei 
Published: October 2022

Abstract
The current study aims to evaluate the associations between 10 urinary polycyclic aromatic hydrocarbon(PAH) metabolites and thyroid profiles. The levels of 10 PAH metabolites and thyroid profiles were obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2012. Spearman analysis was utilized to evaluate the correlation coefficients among these 10 PAH metabolites. Multivariate linear and logistic regression models assessed the relationship between urinary PAH metabolites levels, thyroid hormones, and thyroid autoantibodies after adjusting potential confounders. Stratified analysis by gender was performed to evaluate sex-specific effect of urinary metabolites of PAH on thyroid profiles. 1645 eligible adult participants with complete research data were enrolled. Of note, the concentrations of the majority of urinary PAH metabolites were remarkedly higher in females compared with males. 2-hydroxyfluorene(2-FLU) was associated with higher total triiodothyronine (T3) levels in whole population (β=2.113, 95% CI: 0.339-3.888). In males, positive associations were observed in 1-hydroxynaphthalene (1-NAP) and free thyroxine (T4) (β=0.0002, 95% CI: 0.0000-0.0004), 2-FLU and total T3 (β=2.528, 95% CI: 0.115-4.940). While in female participants, 2-hydroxynaphthalene (2-NAP) was associated with free T3 (β=0.002, 95% CI: 0.000-0.005), 2-FLU was associated with total T3 (β=2.683, 95% CI: 0.038-5.328), free T3 (β=0.050, 95% CI: 0.012-0.087), and total T4 (β=0.195, 95% CI: 0.008-0.382). 2-hydroxyphenanthrene (2-OHP), 1-hydroxypyrene (1-HP) and 9-hydroxyfluorene (9-FLU) were all positively related to total T3 levels, the corresponding coefficients were 16.504, 6.587, and 3.010. 9-FLU was also associated with free T3 (β=0.049, 95% CI: 0.008-0.090). No statistical significances were found between PAH metabolites levels and increased prevalence of increased thyroglobulin antibody (TgAb)/thyroid peroxidase antibody (TPOAb) when PAH metabolites were treated as continuous variables. Meanwhile, in the quartile analyses, increased prevalence of elevated TgAb was observed in participants with quartile 2 2-NAP compared with lowest quartile (OR=1.753, 95% CI: 1.021-3.008). Male subgroup analyses indicated increased prevalence of elevated TgAb was observed in higher quartile of 1-NAP, 2-NAP and 3-hydroxyfluorene(3-FLU). Increased prevalence of elevated TPOAb was associated with higher 2-NAP quartile. However, in subgroup analysis of females, no statistical significances were found between PAH quartiles and increased TgAb/TPOAb. Significant correlations were found among these 10 PAH metabolites. In conclusion, the cross-sectional study indicated exposure to PAH might disturb the concentrations of thyroid hormones and thyroid autoantibodies. It is noteworthy that significant differences existed in males and females. Further prospective research is warranted to explore the causal relationship and underlying mechanism of PAH exposure on thyroid dysfunction.