Hashimoto's thyroiditis: two decades on

Hashimoto's thyroiditis is the most common cause of primary hypothyroidism in iodine-sufficient regions and is characterised by immune-mediated injury to thyroid follicular cells. Its pathophysiology involves an interplay of genetic susceptibility, environmental exposures, and epigenetic modifications that disrupt immune tolerance, promoting T-cell mediated thyroid injury and thyroid autoantibody production. The disease can progress from euthyroid autoimmunity to subclinical and overt hypothyroidism, with substantial variation in its course. Clinical manifestations vary with the extent of thyroid dysfunction and inflammatory activity. Diagnosis relies on clinical assessment, thyroid function testing, thyroid autoantibody measurement, and ultrasonography when indicated. Management centres on levothyroxine replacement for overt hypothyroidism, with an individualised approach to subclinical disease. Thyroidectomy is reserved for selected indications, whereas emerging immunomodulatory strategies remain investigational. This Review synthesises developments over the past two decades in the epidemiology, natural history, aetiopathogenesis, diagnosis, and management of Hashimoto's thyroiditis, and considers emerging mechanistic insights and approaches to precision medicine that might inform future disease-modifying therapies.