Hashimoto’s thyroiditis is best defined as an organ-specific autoimmune disease, characterized by autoimmune-mediated destruction of the thyroid gland. Diagnostic criteria have changed dramatically since the first description in 1912; they now include the presence of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin, hypoechogenicity on thyroid ultrasound, and often but not always hypothyroidism. Distinct pathologic phenotypes are recognized: goitrous and atrophic variants but also an IgG4-related variant, hashitoxicosis, juvenile thyroiditis, and silent or painless thyroiditis. With a prevalence of 10–12% in the general population, it is the most common autoimmune disease. The prevalence is higher in females than in males, increases with advancing age, and is highest in Whites and lowest in Blacks. The incidence of autoimmune hypothyroidism is about 350 cases/100,000/year for women and 60 cases/100,000/year for men in iodine-sufficient regions and 44 (females) and 12 (males) per 100,000 per year in iodine-deficient areas. Breakdown of self-tolerance against thyroid antigens may lead to thyroid autoimmunity. Loss of Treg inhibitory actions and gain of Th17 proinflammatory actions (reflected by a shift to higher values of Th17/Th10 ratio in peripheral blood) play a crucial role in the loss of tolerance against thyroid antigens. Cytotoxic CD8+ T cells directed against TPO and Tg mediate thyroid gland destruction, either by the granule exocytosis pathway or apoptosis (programmed cell death). TPOAb and TgAb may cause antibody-dependent cell-mediated cytotoxicity (ADCC) via complement-mediated lysis of thyrocytes. Hashimoto’s thyroiditis often runs in families as evident from a high sibling risk ratio of 28. Twin studies suggest genes contribute about 73% of the liability to the development of TPOAb and TgAb; environmental factors would thus contribute about 20–30%. Polymorphisms in TSHR, Tg, HLA, CTLA-4, IL2RA, and FOXP3 have all been associated with Hashimoto’s thyroiditis but account for only a small proportion of the heritability. Genome-wide association studies continue to detect novel genetic loci linked to TPOAb. Smoking and moderate alcohol consumption to a certain extent protect against Hashimoto’s thyroiditis. Low selenium or vitamin D intake are presumably related to a higher prevalence of TPOAb, but presently there is no convincing evidence that selenium or vitamin D supplementation may lower TPOAb concentration. Infections may provoke Hashimoto’s thyroiditis, but available epidemiological studies do not support a causative role.
KeywordsHashimoto’s thyroiditis History Diagnosis Epidemiology Immunopathogenesis IgG4 Genetic polymorphisms Environment
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