Exposure to Perfluoroalkyl Substances (PFAS) and Association with Thyroid Hormones in Adolescent Males

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.