Perfluoroalkyl acids and thyroid hormones across stages of kidney function.

Data for US adults aged ≥20 years for 2007-2012 (N = 7020) were used to study concentrations of thyroid stimulating hormone (TSH), free (FT3) and total triiodothyronine (TT3), free (FT4) total thyroxine (TT4), and thyroglobulin (TGN) across stages of glomerular function (GF). Data for 2007-2008 and 2011-2012 (N = 2549) were used to study associations between thyroid hormone biomarkers and five serum perfluoroalkyl acids (PFAAs). We report how thyroid hormone biomarkers vary in human serum across stages of GF. Stages considered were: GF-1 (normal, eGFR >90 mL/min/1.73 m2), GF-2 (60 ≤ eGFR≤90 mL/min/1.73 m2), GF-3A (45 ≤eGFR<60 mL/min/1.73 m2), and GF-3B/4 (15 ≤ eGFR<45 mL/min/1.73 m2). Regression models stratified by GF stages were fitted to evaluate associations between the concentrations of selected PFAAs and thyroid hormones and to evaluate the variability in concentrations of thyroid hormones across the stages of GF. Adjusted geometric means (AGM) for TSH sharply increased from GF-1 (1.34 μIU/mL) to GF-2 (1.58 μIU/mL) and then remained relatively stable. AGMs of FT3 and TT3 decreased consistently from GF-1 to GF-3B/4; from 3.24 to 2.79 pg/mL for FT3 and from 115.7 to 96.4 ng/dL for TT3. AGMs for FT4 increased from GF-2 onward. TGN increased as glomerular filtration worsened from GF-1 through GF-3B/4. In contrast to strong relationships of thyroid hormone markers to stages of renal function, only scattered, inconsistent findings characterized relationship of PFAAs to thyroid markers across stages of kidney disease. For example, TSH was positively associated with PFOA at GF-2 (β = 0.08522, p < 0.01) but negatively associated at GF-3A (β = - 0.22926, p = 0.04). Thus, associations between kidney disease and thyroid hormone are clear, but the relationships between PFAAs and thyroid hormones vary inconsistently from stage to stage and reveal no trend. For thyroid hormone investigations, we conclude stratification by glomerular function stage is likely not needed.

Jain RB ，Ducatman A 《-》

Perfluoroalkyl acids serum concentrations and their relationship to biomarkers of renal failure: Serum and urine albumin, creatinine, and albumin creatinine ratios across the spectrum of glomerular function among US adults.

Jain RB ，Ducatman A 《-》

Perfluoroalkyl substances follow inverted U-shaped distributions across various stages of glomerular function: Implications for future research.

Data (N = 6844) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for the years 2007-2014 were analyzed to evaluate distributional characteristics of selected perfluoroalkyl substances (PFAS) - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) with declining glomerular function. The population was stratified according to the estimated glomerular filtration rates (eGFR) that accompany the stages of kidney disease, designated as glomerular function-1 (GF-1, eGFR>90 mL/min/1.73 m2); GF-2 (eGFR 60-89 mL/min/1.73 m2), GF-3A (eGFR 45-59 mL/min/1.73 m2), and GF-3B and 4 combined (eGFR 15-44 mL/min/1.73 m2). Unadjusted as well as adjusted geometric means for serum PFOA, PFDA, PFHxS, and PFNA increased as expected through stage GF-3A but decreased below the concentrations associated with GF-1 for those who were in GF-3B/4. For example, unadjusted geometric means for PFOA were 2.59, 3.02, 3.01, and 2.22 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Adjusted geometric means for PFOA were 2.34, 2.83, 2.83, and 1.81 ng/mL for GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Thus, PFAS were found to follow inverted U-shaped distributions across different stages of glomerular function. For females, decreases in adjusted PFAS serum levels were initiated at GF-3A, while decreases for males began as early as GF-2. Usually, females are known to have lower levels of PFAS but when in GF-3A and GF-3B/4, females were found to have higher levels of PFAS than males. Thus, inverted U-shaped curves for males and females intersected between GF-2 and GF-3A for PFOA and PFHxS and at GF-3A for PFOS and PFNA. Associations between PFAS and biomarkers of kidney function may be modified in both magnitude and even in direction as kidney function deteriorates. These findings have implications for studies that evaluate associations between PFAS and disease states that affect kidney function, as well as outcome biomarkers known to be affected by kidney function.

Jain RB ，Ducatman A 《-》

Serum Biomarkers of Exposure to Perfluoroalkyl Substances in Relation to Serum Testosterone and Measures of Thyroid Function among Adults and Adolescents from NHANES 2011-2012.

Lewis RC ，Johns LE ，Meeker JD 《-》

Longitudinal analysis reveals early-pregnancy associations between perfluoroalkyl sulfonates and thyroid hormone status in a Canadian prospective birth cohort.

Serum perfluoroalkyl acids (PFAAs) have been linked to disruption of maternal thyroid hormone homeostasis, but results have varied between studies which we hypothesized was due to timing of the thyroid hormone measurements, variability in PFAA isomer patterns, or presence of other stressors. In a longitudinal study design, we investigated the time-dependency of associations between PFAA isomers and thyroid hormones during pregnancy and post-partum while considering thyroid peroxidase antibody (TPOAb) status and mercury (Hg) co-exposure. In participants of a prospective Canadian birth cohort (n = 494), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH) and TPOAb were quantified in maternal plasma collected in each trimester and 3-months postpartum, and 25 PFAAs (15 linear and 10 branched) and Hg were quantified in samples collected during the second trimester. Perfluorohexane sulfonate (PFHxS) and total branched isomers of perfluorooctane sulfonate (PFOS) were positively associated with TSH in mixed-effect models, with strongest associations early in gestation. Throughout pregnancy and post-partum, PFHxS was inversely associated with FT4, consistent with elevated TSH, while Hg was inversely associated with FT3. In TPOAb-positive women, negative associations were found between PFUnA and FT4, and 1m-PFOS and TSH, supporting previous studies that thyroid disorder could increase susceptibility to PFAA-mediated hormone dysregulation. Hg did not confound associations but was a significant interaction term, revealing further positive associations between PFOS isomers (∑3m+4m-PFOS) and TSH. Higher perfluoroalkyl sulfonate exposures were associated with higher TSH and/or lower FT4, strongly suggestive that PFHxS and branched PFOS isomers are risk factors for subclinical maternal hypothyroidism. Isomer-specific analysis is important in future studies, as crude measures of 'total-PFOS' masked the associations of branched isomers. A concerning result was for PFHxS which had consistent negative associations with FT4 at all time points and a positive association with TSH in early pregnancy when fetal development is most sensitive to disruption.

Reardon AJF ，Khodayari Moez E ，Dinu I ，Goruk S ，Field CJ ，Kinniburgh DW ，MacDonald AM ，Martin JW ，APrON Study ... -  《-》