2023: Exposure to perfluoroalkyl substances (PFAS) and association with thyroid hormones in adolescent males

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Freire C, Vela-Soria F, Castiello F, Salamanca-Fernández E, Quesada-Jiménez R, López-Alados MC, Fernandez MF, Olea N - "Exposure to perfluoroalkyl substances (PFAS) and association with thyroid hormones in adolescent males" Int J Hyg Environ Health 252:114219 (2023). doi: 10.1016/j.ijheh.2023.114219

Abstract
Background: Perfluoroalkyl substances (PFAS) are found in a wide range of consumer products. Exposure to PFAS in children and adolescents may be associated with alterations in thyroid hormones, which have critical roles in brain function.

Objective: This study investigated the association between plasma concentrations of PFAS and serum levels of total triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) in adolescent males.

Methods: In 2017-2019, 151 boys from the Environment and Childhood (INMA)-Granada birth cohort, Spain, participated in a clinical follow up visit at the age of 15-17 years. Plasma concentrations of ten PFAS (PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFOS, and PFHxS) and serum thyroid hormones were measured in 129 of these boys. Linear regression analysis was performed to determine associations of individual PFAS with total T3, free T4, TSH, and free T4/TSH ratio, and quantile g-computation models were performed to assess the mixture effect. Additional models considered iodine status as effect modifier.

Results: PFOS was the most abundant PFAS in plasma (median = 2.22 μg/L), followed by PFOA (median = 1.00 μg/L), PFNA (median = 0.41 μg/L), and PFHxS (median = 0.40 μg/L). When adjusted by confounders (including age, maternal schooling, and fish intake), PFOA and PFUnDA were associated with an increase in free T4 (β [95% CI] = 0.72 [0.06; 1.38] and 0.36 [0.04; 0.68] pmol/L, respectively, per two-fold increase in plasma concentrations), with no change in TSH. PFOS, the sum of PFOA, PFNA, PFOS, and PFHxS, and the sum of long-chain PFAS were marginally associated with increases in free T4. Associations with higher free T4 and/or total T3 were seen for several PFAS in boys with lower iodine intake (<108 μ/day) alone. Moreover, the PFAS mixture was association with an increase in free T4 levels in boys with lower iodine intake (% change [95% CI] = 6.47 [-0.69; 14.11] per each quartile increase in the mixture concentration).

Conclusions: Exposure to PFAS, considered individually or as a mixture, was associated with an increase in free T4 levels in boys with lower iodine intake. However, given the small sample size, the extent of these alterations remains uncertain.

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Kim HY, Kim KN, Shin CH, Lim YH, Kim JI, Kim BN, Hong YC, Lee YA - "The Relationship Between Perfluoroalkyl Substances Concentrations and Thyroid Function in Early Childhood: A Prospective Cohort Study" Thyroid 30(11):1556-1565 (2020). doi: 10.1089/thy.2019.0436.
https://www.liebertpub.com/doi/10.1089/thy.2019.0436

Abstract

Background: Exposure to perfluoroalkyl substances (PFAS) has been suggested to affect thyroid function; however, data on early-life exposure and thyroid function in early childhood are scarce. We investigated the cross-sectional and longitudinal relationships of early-life exposure to PFAS with thyroid function at 2, 4, and 6 years of age. Methods: This study used data on PFAS exposure and thyroid function from the Environment and Development of Children (EDC) cohort study. A total of 660 children who visited at least once at 2, 4, or 6 years of age (381 children aged 2 years, 569 children aged 4 years, and 511 children aged 6 years) were included in this study. Serum thyrotropin (TSH) levels were measured at 2, 4, and 6 years of age. The relationship of serum PFAS (sPFAS) concentrations with TSH levels at the three time points was assessed by repeated-measure analysis using linear mixed models. The serum levels of free thyroxine (fT4) and triiodothyronine (T3) were measured once (at 6 years of age). The relationship of sPFAS with fT4 and T3 levels at 6 years of age was investigated by linear regression analyses. Results: None complained of hyper- or hypothyroid symptoms with normal fT4 and T3 levels. Repeated-measure analysis showed that TSH levels at 2, 4, and 6 years of age were inversely associated with serum perfluorononanoic acid (sPFNA), after adjusting for age, sex, and/or dietary iodine intake (p < 0.05). When stratified by sex, TSH levels were inversely associated with serum perfluorooctanoic acid (sPFOA) in boys and sPFNA in girls (p < 0.05 for both). fT4 levels at 6 years of age were positively related to sPFNA and serum perfluorohexane sulfonic acid at 2 years of age and sPFOA at 6 years of age, and T3 levels at 6 years of age showed positive relationships with serum perfluorodecanoic acid and serum perfluorooctane sulfonic acid at 6 years of age (p < 0.05 for all). When stratified by sex, similar positive relationships for sPFAS with fT4 and T3 levels were significant among boys only. Conclusions: A significant relationship was found between early-life exposure to PFAS and thyroid function. Early-life exposure to PFAS was associated with decreased TSH and increased fT4 or T3 levels among preschool-age children.