Written by Angeline A. De Leon, Staff Writer. This study finds that chemical pollutant mixtures function as thyroid disruptors, with polychlorinated bisphenols (PCBs) and its metabolites specifically linked to hypothyroidism.
Thyroid disorders involve alterations in the production of thyroid hormones, as in the case of Hashimoto’s disease and Graves’ disease, the former characterized by hypothyroidism and the latter hyperthyroidism 1. Epidemiological evidence suggests that the risk of autoimmune thyroid disease is elevated among individuals exposed to high levels of environmental pollutants 2, however, newer research suggests that this risk may be a cumulative result of exposure to a mixture of pollutants, rather than a single specific chemical 3,4. According to the “multiple hit hypothesis”, individuals exposed to multiple stressors of the thyroid, triggered to increase production of autoimmune thyroid antibodies, will subsequently develop greater vulnerability to thyroid disruption by chemical pollutants 5. Among the toxic chemicals recognized as thyroid disruptors with additive or synergistic effects are persistent organic pollutants (POPs), which include polychlorinated biphenyls (PCBs), organochlorine pesticides, and perfluoroalkyl substances (PFASs) 6,7. Indeed, studies show that high concentrations of PCBs are associated with alterations in thyroid hormone levels 8, and high levels of PFASs are associated with increased incidence of thyroid disorders 9. In a 2020 study 10 published in Environmental Research, researchers in Belgium sought to parse from a larger mixture of pollutants the individual thyroid disruptors associated with autoimmune thyroid pathology.
In a case-control study, a total of 35 patients with Hashimoto’s hypothyroidism and 44 patients with Graves’ hyperthyroidism (mean age = 43.8 years) were matched by sex and age to healthy control subjects (70 assigned as controls for hypothyroidism, 90 for hyperthyroidism) (mean age = 44.1 years). All participants provided blood samples which were analyzed to determine the concentrations of 12 brominated flame retardants (BFRs), 3 PCBs, 16 organochlorine pesticides, 7 PFASs, and 16 phenolic organohalogens (POHs). Weighted quantile sum (WQS) regressions were used to calculate indices representing the mixture of POPs (WQS index), and the association between WQS index and thyroid pathology status was determined.
Data analyses identified 19 pollutants (6 PFASs, 9 POHs, 1 organochlorine pesticide, and 3 PCBs) which were detected in over 40% of participants and, therefore, included in WQS indices. WQS regression models revealed that each quartile increase of the WQS index was related to a higher risk of an autoimmune thyroid pathology (Odds Ratio = 4.83, 95% Confidence Interval: 1.38 to 16.9) and hypothyroidism (OR = 98.1, 95% CI: 5.51 to 1747), but not higher risk of hyperthyroidism (OR = 0.57, 95% CI: 0.11 to 2.99). The most heavily weighted POPs contributing to the association between pollutant mixture and autoimmune thyroid pathology were 3-OH-CB 180 (weight = 0.249), PCB 138 (w = 0.190), and 4,4’-DDE (w = 0.180). For hypothyroidism, the chemicals with the highest weighted index profiles were PCB 138 (w = 0.210), 3-OH-CB 180 (w = 0.197), and 4-OH-CB 146 (w = 0.188).
Evidence from the current investigation sheds light on how mixtures of chemical pollutants can contribute to endocrine disruption in human subjects. More specifically, results suggest the possibility that hypothyroidism and hyperthyroidism are each associated with distinct profiles of pollutants, with hypothyroidism being positively linked to PCB and PCB metabolites. Additional work is needed to better understand the pathological pathways involved in relating specific pollutants with each disorder. Various study limitations should also be taken into account, including the case-control design of the trial, its relatively small sample size, the enrollment of case subjects who were undergoing treatment at the time of the study, and the failure to control for confounding variables such as lipid profile. As a preliminary, hypothesis-generating study, the current trial highlights the value of exploring the role of chemical mixtures in autoimmune thyroid disorders.
Source: Dufour P, Pirard C, Petrossians P, et al. Association between mixture of persistent organic pollutants and thyroid pathologies in a Belgian population. Environmental Research. 2020; 181: 108922. DOI: 10.1016/j.envres.2019.108922.
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Posted September 8, 2020.
References:
- McLeod DS, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine. 2012;42(2):252-265.
- Langer P, Kocan A, Tajtáková M, et al. Possible effects of persistent organochlorinated pollutants cocktail on thyroid hormone levels and pituitary-thyroid interrelations. Chemosphere. 2007;70(1):110-118.
- Kortenkamp A. Low dose mixture effects of endocrine disrupters and their implications for regulatory thresholds in chemical risk assessment. Curr Opin Pharmacol. 2014;19:105-111.
- Villa S, Migliorati S, Monti GS, Vighi M. Toxicity on the luminescent bacterium Vibrio fischeri (Beijerinck). II: Response to complex mixtures of heterogeneous chemicals at low levels of individual components. Ecotoxicology and environmental safety. 2012;86:93-100.
- Webster GM, Venners SA, Mattman A, Martin JW. Associations between perfluoroalkyl acids (PFASs) and maternal thyroid hormones in early pregnancy: a population-based cohort study. Environ Res. 2014;133:338-347.
- Boas M, Feldt-Rasmussen U, Main KM. Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol. 2012;355(2):240-248.
- Miller VM, Sanchez-Morrissey S, Brosch KO, Seegal RF. Developmental coexposure to polychlorinated biphenyls and polybrominated diphenyl ethers has additive effects on circulating thyroxine levels in rats. Toxicological sciences : an official journal of the Society of Toxicology. 2012;127(1):76-83.
- Benson K, Yang E, Dutton N, Sjodin A, Rosenbaum PF, Pavuk M. Polychlorinated biphenyls, indicators of thyroid function and thyroid autoantibodies in the Anniston Community Health Survey I (ACHS-I). Chemosphere. 2018;195:156-165.
- Lopez-Espinosa M-J, Mondal D, Armstrong B, Bloom MS, Fletcher T. Thyroid function and perfluoroalkyl acids in children living near a chemical plant. Environmental health perspectives. 2012;120(7):1036.
- Dufour P, Pirard C, Petrossians P, Beckers A, Charlier C. Association between mixture of persistent organic pollutants and thyroid pathologies in a Belgian population. Environ Res. 2020;181:108922.