Autoimmune Thyroid Disease-Immune and Environment
The autoimmune disease I want to discuss is autoimmune thyroid disease (Hashimoto’s). According Mark Hyman, “it’s not just your genes; your environment could be harming your thyroid” (Hyman, n.d.). Hashimoto’s thyroiditis is the most frequent organ specific, T-cell mediated autoimmune disorder (Kisakol, 2014). It is a complex disease, with a strong genetic component (Burek & Talor, 2009). “Infiltrating lymphocytes and T cell mediated cytotoxicity are involved in the pathogenesis of autoimmune thyroiditis” (Kisakol, 2014). The number of diagnosed Hashimoto’s cases has been on the constant increase since the 1950s, making it one of the most common autoimmune diseases today. Such a rapid increase cannot be explained by only inherited changes within our genes due to the time it takes to acquire and transfer gene mutations (Tabor, 2017). “The overt disease is defined by the dramatic loss of thyroid follicular cells (thyrocytes), hypothyroidism, goiter, circulating autoantibodies to two primary thyroid specific antigens, thyroglobulin (Tg), thyroid peroxidase (TPO), and lowered concentrations of serum TSH and T4” (Burek & Talor, 2009).
Autoimmune thyroid disease is characterized by the breakdown of immunological self-tolerance. This breakdown is thought to result in the presentation of host autoantigens and expansion of autoreactive lymphocyte clones, in the context of MHC class II haplotypes and other immune and regulatory genes (Chistiakov, 2005). There are theories that the thyroid abnormally expresses MHC molecules and presents disease-causing antigens directly to T-cells. In addition, excessive iodine can lead to elevated ROS expression in the thyroid, as it is rapidly oxidized by TPO, which thus damages the thyrocyte cell membrane. An influx of dendritic cells and macrophages to the thyroid may occur as a consequence of inflammatory events in the gland, due to toxins or infections, that can cause early death of thyroid cells. According to Vojdani (2014), “a dysregulated immune response to environmental triggers, such as pathogens, microbiota, or toxins, can initiate a chronic inflammatory response through activation of Thelper-1 (Th1), Th17, and TNF-𝛼 and the production of IL17, IL-22, interferon-gamma (IFN-𝛾), and IL-21, resulting in inflammation, antibody production and tissue injury” (Vojdani, 2014). Overactive innate immune response, development of effector T and B cells, and defects in regulatory T cells results in a breakdown of immune homeostasis and development of autoimmunity. Therefore it’s a dysregulated adaptive immune system that is at the core of the pathogenesis of autoimmune disease such as AITD.
Environmental agents can interfere with the thyroid function at multiple sites, including thyroid hormone production, metabolism and excretion, and action (Brent, 2010). “Most of these agents reduce circulating thyroid hormone levels or impair thyroid hormone action, although some may inﬂuence the pituitary and thyrotropin (TSH) secretion, or even be partial thyroid hormone receptor agonists” (Brent, 2010). Although there tends to be a genetic predisposition, the environment is strongly associated with triggering autoimmune thyroid disease (AITD), providing about a 20-30% contribution to its onset (Brent, 2010). Various exposures have been proposed, such as radiation exposure, infections, smoking, gluten and milk proteins, iodine deficiency, heavy metal exposure and other toxins. For this brief review, I would like to focus on radiation, microbes, diet and heavy metals (mercury).
- Radiation exposure
There are some studies that indicate that the prevalence of AITD is higher in people exposed to radiation, as seen in incidents involving the Chernobyl accident (Ferrari, Fallahi, Antonelli, & Benvenga, 2017). The radiation dose was related to an increased TPOAb prevalence. Additionally, toxic goiter treatment with radioiodine has been associated with the onset of Grave’s disease. Thyroid ionizing radiation is associated with tardive hypothyroidism, thyroid nodules, and thyroid cancer (Ferrari et al., 2017).
Microbes are associated with AITD. In one view, intestinal dysbiosis and permeability can result in immune dysfunction, due to epithelial barrier failure. This can lead to impaired metabolism of nutrients, drugs, hormones and other exogenous and endogenous substances that are involved directly or indirectly in thyroid homeostasis. Some viruses are also associated with AITD. Human T-cell lymphotropic virus-1, herpes simplex, rubella, mumps, Epstein-Barr, and Hepatitis-C (HCV) are all implicated in the etiology of AITD. HCV, in particular, interferes with the functions and self-recognition mechanism in the immune system, leading to destruction of the thyroid and start of autoimmune disease (Ferrari et al., 2017). Other infections that have been associated with AITD include intestinal infections such as H. plyori (Hyman, n.d.) and Blastocystis hominis (Rajic et al., 2015).
3. Dietary influence-Various dietary influences are associated with AITD, as briefly listed below
- Iodine intake
Iodine is essential for thyroid function. Iodine intake in the US has been steadily declining, although recent studies show the intake is stabilizing. Deficient iodine intake is known to be associated with reduced thyroid hormone production (Brent, 2010). However, excessive iodine, as often see in over consumption of iodized salt, has also been associated with autoimmune thyroid (Foley, 1992). In response to iodine supplementation in areas of iodine deﬁciency, there is an increase in thyroid autoantibodies and in some cases autoimmune thyroid disease (Brent, 2010). Studies have shown that excess iodine can cause thyroid injury by generating ROS, which can lead to premature damage in thyroid tissues, particularly in the context of selenium deficiency (Wentz, 2017). The recommendation is not to exceed 200mcg/day of iodine, which includes intake from foods that are high in iodine. When exposed to higher doses of iodine, it may be helpful to supplement with selenium as well.
- Vitamin D deficiency
There is increasing epidemiologic evidence linking vitamin D deficiency and autoimmune diseases, (Aranow, 2011). Vitamin demonstrates to have a pleiotropic role in the immune system, and may be involved in the autoimmune process. “Observational studies have documented an inverse relation between serum levels of 25-hydroxyvitamin D (25[OH] D) and thyroid peroxidase antibody (TPO-Ab)” (Chaudhary et al., 2016) In fact a study published in 2016 indicates that Vitamin D supplementation in AITD may be able to reduce TPO-Ab titers (Chaudhary et al., 2016).
- Selenium intake
Adequate selenium is required for efficient thyroid synthesis and metabolism, while protecting the thyroid gland from damage from excessive iodine (Kresser, 2012). Selenium is essential for conversion of T4 to T3, since the enzymes for the conversion of selenium dependent. A study in 2007 demonstrated that 12 months of treatment with L-selenomethionine caused a decreased in serum anti-TPO levels (Mazokopakis et al., 2007)
- Dietary proteins
The exact mechanisms of the influence dietary proteins in AITD in not well understood, but it is thought that the mechanisms involves molecular mimicry between gliadin or transglutaminase and various tissue antigens, such as the thyroid tissue (Vojdani, 2014). Evidence collected from studies indicate that circulating antibodies can interact with different food antigens and transglutaminases in various tissues. This may induce the formation of antigen-antibody aggregates that can trigger the activation of the inflammatory cascade (Vojdani, 2014). This is particularly seen in the context of Celiac Disease as well as non-celiac gluten sensitivity. According to Vojdani (2014), several studies also suggest that dysregulation of oral tolerance triggers a cellular and humoral immune response against various components of milk proteins, and cross-reaction with B-cell molecules may result in autoimmunity. Therefore, it is often recommended that people with autoimmune thyroid eliminate wheat and dairy from their diet. Other foods that demonstrated immune reactivity include cow’s milk, milk chocolate, whey protein, casein, yeast, oats, corn, millet, instant coffee and rice (Vojdani, 2014)
- Heavy metals exposure (particularly Mercury)
Disruption of thyroid hormone (TH) synthesis, transport, deiodination, and metabolism, from environmental factors, can result in clinical or subclinical thyroid diseases (Chen, Kim, Chung, & Dietrich, 2013). Proposed mechanisms of mercury related TH disruption involve “selective binding to sulfhydryl (SH)containing ligands in the thyroid, reduced TSH production, and inhibition of deiodination” (Chen et al., 2013). A study published in 2011 found that women with elevated mercury exposure were more than twice as likely to have thyroid antibodies, which suggest a positive association between mercury and thyroid peroxidase autoantibody (Gallagher & Meliker, 2012). It should be pointed out that studies of populations with environmental exposure, for example, from fish consumption and from dental amalgams, also have had mixed findings (Chen et al., 2013).
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