Hashimoto's Thyroiditis - Risk Factors

Risk Factors

A family history of thyroid disorders is common, with the HLA-DR5 gene most strongly implicated conferring a relative risk of 3 in the UK. In addition Hashimoto's thyroiditis may be associated with CTLA-4(Cytotoxic T-lymphocyte Associated-4) gene polymorphisms that result in reduced functioning of the gene's products, which are associated with negative regulation of T-lymphocyte activity. Downregulatory gene polymorphisms affecting CTLA4 are also associated with autoimmune pathology seen in development of Type I diabetes. The strong genetic component underscoring this theory is born out in studies on monozygotic twins, with a concordance of 38-55%, with an even higher concordance of circulating thyroid antibodies not in relation to clinical presentation (up to 80% in monozygotic twins). Neither result was seen to a similar degree in dizygotic twins, offering strong favour for high genetic aetiology.

Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of autoimmune thyroid disease in genetically predisposed individuals. The genes implicated vary in different ethnic groups and the incidence is increased in patients with chromosomal disorders, including Turner, Down's, and Klinefelter syndromes usually associated with autoantibodies against thyroglobulin and thyroperoxidase. Progressive depletion of these cells as the cytotoxic immune response develops leads to higher degrees of primary hypothyroidism, presenting with a poverty of T3/T4 levels, and compensatory elevations of TSH.