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.