Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne Mohawk young adults

Abstract

Persistent organic pollutants, such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and p,p′-dichlorophenyldichloroethylene (DDE), have been found to elicit a broad spectrum of biologic, metabolic, and immunologic responses. The potential of these pollutants to impair immune responses and trigger autoimmune disease is of growing concern, given their structural similarity to thyroid hormones and their potential to modulate the mechanisms and interfere with the binding of these hormones. We examine the relationship of different groupings of PCBs, according to chlorination and structure, and of p,p′-DDE and HCB to anti-thyroid peroxidase antibody, a useful tool in the evaluation of thyroid dysfunction, among 115 young adults of the Akwesasne Mohawk Nation.

Overall, 18 participants (15.4%) had anti-thyroid peroxidase antibodies (TPOAb) levels above the normal laboratory reference range (23% of females, 9% of males). Among participants who were breast fed (n=47), those with an elevated TPOAb level had significantly higher levels of all PCB groupings, with the exception of levels of non-persistent PCBs which did not differ significantly. Levels of p,p′-DDE were also significantly elevated, while HCB and mirex were not higher among those with elevated TPOAb. Also, after stratifying by breast-feeding status, participants who were breast fed showed significant, positive relationships between TPOAb levels and all PCB groupings, except groups comprised of non-persistent PCBs, and with p,p′-DDE, HCB, and mirex. No effects were evident among non-breast-fed young adults.

Further studies are necessary to elucidate the site and mechanism of action of these persistent organic pollutants (POPs) and to establish thresholds for these effects, especially among populations with background levels of toxicant exposure.

Introduction

Polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs), such as hexachlorobenzene (HCB), and p,p′-dichlorophenyldichloroethylene (p,p′-DDE), a metabolite of p,p′-DDT, have been found to elicit a broad spectrum of biologic, metabolic, and immunologic responses (ATSDR, 2000; Hagmar, 2003; Safe, 2001, Safe, 2000). The potential of these POPs to impair immune responses and trigger autoimmune disease is of growing concern. Given the structural similarity to thyroid hormones, PCBs (and/or their biphenylol metabolites) may mimic thyroid hormone action and even modulate the mechanisms and interfere with the binding of these hormones (Langer et al., 2007; Meeker et al., 2007; Zoeller, 2007, Zoeller, 2001), potentially leading to thyroid functional disorders and autoimmune thyroid diseases (Barsano, 1981; Murai et al., 1987).

Autoantibodies to thyroid peroxidase (TPOAb) can attack the thyroid and damage thyroid function (Larsen et al., 2003). While not a test of thyroid function, serum TPOAb titers are useful as a biomarker of thyroid dysfunction, as well as a diagnostic tool for many idiopathic autoimmune diseases such as chronic thyroiditis (Langer et al., 1998, Langer et al., 2007), Hashimoto's encephalopathy (Mocellin et al., 2007), Grave's disease (Antonelli et al., 2006), systemic lupus erythematosus (Kohno et al., 1989), and connective tissue disorders such as Sjogren syndrome (Tunc et al., 2004) and rheumatoid arthritis (Lee et al., 2007). The likelihood of damage appears to be greater in females, and increases with age (Antonelli et al., 2006; Lee et al., 2007).

Autoimmune dysfunction is thought to disrupt normal hypothalamic–pituitary–gonadal function and thereby affect reproductive outcomes, such as an increased risk of pregnancy loss (Djursing et al., 1982; Gleicher et al., 1993; Kjaer et al., 1992), and has been linked to the impairment of female fecundity even before the diseases become clinically overt (Nelson et al., 1993). Elevated TPOAb levels have been linked to autoimmune hypo- and hyperthyroidism in pregnancy, immune-mediated miscarriages, and an increased risk for postpartum thyroiditis (Adcock et al., 1994; Matarese et al., 2003).

Here we examine the relationship of different PCB groupings, according to chlorination level and substitution pattern, along with p,p′-DDE and HCB, to anti-thyroid peroxidase antibody among young adults of the Akwesasne Mohawk Nation (AMN).