Etiology of Hashimoto's Thyroiditis: A Literature Review of Genetic, Environmental, Epigenetic, and Immunologic Factors

ABSTRACT Hashimoto’s thyroiditis (HT) is the most prevalent autoimmune thyroid disorder, affecting ~1–2% of adults, with a 7–10-fold higher incidence in women. The disease involves chronic inflammation, anti-thyroid antibody production, and progressive thyroid failure, particularly in iodine-replete regions. This review aims to consolidate current evidence on HT’s etiology, encompassing genetic factors, environmental exposures, epigenetic regulation, and immunologic mechanisms, as well as highlight future research and intervention directions.The review was based on research of articles published in the PubMed database using the following keywords: Hashimoto’s thyroiditis, autoimmune thyroid disease, thyroid autoimmunity, genetic susceptibility, HLA, CTLA-4, PTPN22, FOXP3, environmental triggers, iodine, Epstein-Barr virus, gut microbiota, vitamin D, oxidative stress, immunopathogenesis, T regulatory cells, Th1, Th17, thyroid peroxidase, thyroglobulin, and apoptosis. The analysis integrates molecular and cellular mechanisms, recent clinical findings, and immunological models to provide a comprehensive and up-to-date understanding of the disease.Recent studies confirm that HT arises from a multifactorial combination of genetic, environmental, and immunological factors. The growing body of evidence from immunogenetic and molecular studies supports a model in which impaired immune regulation, triggered by exogenous factors, leads to chronic lymphocytic infiltration of the thyroid gland. Understanding these mechanisms not only enhances diagnostic accuracy but also offers insight into future therapeutic interventions, including vitamin D supplementation, microbiota modulation, and targeted immunotherapies. Continued research in immunogenomics, environmental epidemiology, and cellular immunology is crucial for identifying individuals at risk and developing strategies to prevent, delay, or modify the course of the disease. KEYWORDS: Hashimoto’s thyroiditis, autoimmune thyroid disease, genetic susceptibility, environmental triggers, oxidative stress.