Severe hypothyroidism is associated with mutations leading to lower production of IL-4 (Th2 cytokine suppressing cell-mediated autoimmunity), lower secretion of TGF-β (inhibitor of cytokine production), and mutations of FoxP3, an essential regulatory factor for the Tregs development. Development of Hashimotos disease was associated with mutation of the gene for TNF-α (stimulator of the IFN-γ production), causing its higher concentration.Preventable environmental factors, including high iodine intake, selenium deficiency, and infectious diseases and certain drugs, have been implicated in the development of autoimmune thyroid disease in genetically predisposed individuals. Iodine
Excessive iodine intake is a well-established environmental factor for triggering thyroid autoimmunity. A higher prevalence of thyroid autoantibodies is in the areas with higher iodine supply. Several mechanisms by which iodine may promote thyroid autoimmunity have been proposed. Iodine exposure leads to higher iodination of thyroglobulin, increasing its immunogenicity by creating new iodine-containing epitopes or exposing cryptic epitopes. It may facilitate presentation by APC, enhance the binding affinity of the T-cell receptor, and activating specific T-cells.Iodine exposure has been shown to increase the level of reactive oxygen species. They enhance the expression of the intracellular adhesion molecule-1 on the thyroid follicular cells, which could attract the immunocompetent cells into the thyroid gland.Iodine is toxic to thyrocytes since highly reactive oxygen species may bind to membrane lipids and proteins. It causes thyrocyte damage and the release of autoantigens.
Though it may occur at any age, including in children, it is most often observed in women between 30 and 60 years of age. The highest prevalence from one study was found in the elderly members of the community.Those that already have an autoimmune disease are at greater risk of developing Hashimotos as the diseases generally coexist with each other. Common diseases seen coexisting with Hashimotos include celiac disease, multiple sclerosis, type 1 diabetes, vitiligo, and rheumatoid arthritis.Congenital hypothyroidism affects 1 in 3500-4000 newborns at birth and is a version of intellectual disability that can be treated if caught early, but can be hard to diagnose given that symptoms are minimal at a young age. Congenital hypothyroidism is generally caused by defects of the thyroid gland, but for most cases in Europe, Asia, and Africa, the iodine intake can cause hypothyroidism in newborns. Geographic influence of dietary trends
Diets consisting of low or high iodine intake determine a populations risk of developing thyroid-related disorders. It is more common in regions of high iodine dietary intake, and among people who are genetically susceptible. Geography plays a large role in which regions have access to diets with low or high iodine. Iodine levels in both water and salt should be heavily monitored in order to protect at-risk populations from developing hypothyroidism.Geographic trends of hypothyroidism vary across the world as different places have different ways of defining disease and reporting cases.