Hashimoto thyroiditis (HT), a classic type of autoimmune thyroiditis (AIT), was first described in 1912 by Japanese scholar Hakaru Hashimoto. It is characterized by significant thyroid enlargement and is a leading cause of primary hypothyroidism. The prevalence of HT ranges from 1% to 10%, with women being affected 3–4 times more often than men. The most common age of onset is between 30 and 50 years.
Etiology and Pathogenesis
The exact cause of HT remains unclear, but it is associated with autoimmune mechanisms and has a hereditary predisposition. Several factors suggest the involvement of autoimmune processes:
- Significant lymphocytic infiltration of the thyroid, along with the participation of cytotoxic T cells and Th1-type cytokines in inflammatory damage.
- The presence of high titers of TPOAb or TgAb in the blood, with TPOAb exhibiting antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxic effects.
- Frequent coexistence with other autoimmune diseases, such as Sjögren’s syndrome, systemic lupus erythematosus, and type 1 diabetes.
- The intermittent presence of TSH receptor antibodies (TSAb and TBAb) in some patients, leading to fluctuations in thyroid function.
- Iodine intake levels are a key environmental factor influencing the development and progression of HT.
Pathology
The thyroid gland is diffusely enlarged and has a firm texture. Histologically, there is extensive infiltration of lymphocytes and plasma cells, forming lymphoid germinal centers. Destruction of thyroid follicular structures is observed, with follicles becoming smaller, atrophic, and containing sparse colloid. Residual follicular cells are hypertrophic with eosinophilic cytoplasm, a feature known as Askanazy cells. As the disease progresses, varying degrees of fibrosis appear. In cases of hypothyroidism, approximately 90% of thyroid follicles are destroyed.
Clinical Manifestations
Most cases present with symptoms of thyroid enlargement or hypothyroidism. In the early stages, there are no clinical symptoms, and the only findings may be TPOAb or TgAb positivity with normal thyroid function. Physical examination may reveal mild to moderate diffuse enlargement of both thyroid lobes with a firm texture and no tenderness.
A minority of patients may experience symptoms of thyrotoxicosis in the early disease stages, caused by follicular destruction and the release of thyroid hormones into the bloodstream. After a brief phase of thyrotoxicosis, thyroid function often returns to normal, though some cases may progress to persistent hypothyroidism.
If high titers of TRAb are present, the two subtypes of TRAb—TSAb and TBAb—may alternate, resulting in patients presenting at different times with clinical features of Graves' disease (hyperthyroidism) or Hashimoto thyroiditis (hypothyroidism).
Laboratory Findings
Significantly elevated titers of TPOAb and/or TgAb are the most relevant diagnostic markers. In hypothyroidism, TSH levels are elevated, while TT4 and FT4 are normal or reduced. The 131I uptake rate is decreased, and thyroid radionuclide scans show uneven distribution. Thyroid ultrasound typically reveals diffuse thyroid enlargement with heterogeneous, reticular echotexture, sometimes accompanied by nodules.
Diagnosis and Differential Diagnosis
Diffuse thyroid enlargement with a firm texture, particularly with an enlarged isthmus or pyramidal lobe, along with significantly elevated serum TPOAb or TgAb levels, confirms the diagnosis of HT. HT can coexist with euthyroidism, hyperthyroidism, or hypothyroidism.
The firm texture of the thyroid in HT necessitates differentiation from thyroid cancer. Patients with HT who develop rapidly growing thyroid nodules or exhibit signs suggestive of malignancy should undergo fine-needle aspiration cytology for evaluation. IgG4-related thyroiditis has clinical features resembling HT, but elevated serum IgG4 levels and core-needle pathology are necessary for definitive diagnosis.
Treatment
There are currently no treatments targeting the underlying cause of HT. Patients with thyroid enlargement but without hypothyroidism typically do not require treatment. Patients with significant thyroid enlargement or hypothyroidism require treatment with levothyroxine (L-T4). For those experiencing severe compressive symptoms unresponsive to medication, surgical treatment may be considered; however, the risk of postoperative hypothyroidism is high.