Hashimoto thyroiditis is the most common cause of hypothyroidism in areas of the world where iodine levels are sufficient. It is characterized by gradual thyroid failure because of autoimmune destruction of the thyroid failure because of autoimmune destruction of the thyroid gland: The name Hashimoto thyroiditis is derived from the 1912 report by Hashimoto describing patients with goiter and intense lympocytic infiltration of the thyroid (e.g., struma lymphomatosa). This disorder is most prevalent between 45 and 65 years of age and is more common in women than men, with a female predominance of 10:1 to 20:1. Although it is a primarily a disease of older women, it can occur in children and is a major cause of nonendemic goiter in children. The disease clusters in families and the concordance rate in monozygotic twins is 30 to 60%. Some cases Some cases of Hashimoto throiditis are associated with HLA-DR5 ; a majority are characterised by severe thyroid atrophy and are linked to HLA-DR3. This suggests that two different pathogenic mechanisma may play a role in the development of the disorder. The usual course of Hashimoto thyroiditis is gradual loss of thyroid function although the inflammatory process early in the disorder may be sufficiently severe to cause thyroid follicular disruption and transient hyperthyroidism. The frequency of other autoimmune disorders, such as systemic lupus erythematosus and rhematoid arthritis , is increased in patients with Hashimoto disease as it is in individuals with Graves disease.

Although both cellular and humoral factors contribute to thyroid injury and hypothyroidism in Hashimoto thyroiditis this disease is believed to be caused primarily by a defect in T cells. One model for this disorder proposes that T cells from patients with this disorde recognize processed thyroid antigens in association with specific types of major histocompatibility complex antigens. Diminished suppressor T cells may also play a role in the emergence of thyroid specific helper T cells. These activated T cells have two roles in the disease: (1) They interact with B cells and stimulate the secretion of a variety of anithyroid antibodies, which may activate antibody dependent cytotoxicity mechanisms and (2) the helper T cells may induce the formation of CD8+ cells which can be cytotoxic to thyroid cells.

B lymphocytes from thyroid tissue of patients with Hashimoto thyroiditis are activated and secrete a number of autoantibodies directed against thyroid antigens:

Thyroglobulin and thyroid preoxidase : Thyroglobulin is synthesized by follicular cells and secreted into the lumen of the thyroid follicle where it is stored as colloid. Thyroid peroxidase is located on the luminal surface of the microvilli of thyroid epithelial cells and catalyzes both tyrosine iodination and coupline of idotyrosyl residues to form T3 and T4. Nearly all patients with Hashimoto thyroiditis have antibodies to both thyroglobulin and thyroid peroxidase, although these autoantibodies are not specific for the disorder. The induction of experimental autoimmune thyroiditis using either thyroglobulin or thyroid peroxidase as antigens provides support for their potential role Hashimoto thyroiditis.

TSH receptor: This is a G protein- coupled transmenbrane receptor. TSH receptor antibodies are specific for Hashimoto and Graves disease, in contrast to the antibodies to thyroglobulin and thyroid peroxidase which are found in patients with many other thyroid disease. In Hashimoto disease the anti TSH receptor antibodies block the action of TSH thus accounting for the hypothyroidism whereas in Graves disease the antibody can have a thyroid stimulating activity.

Iodine transporter: Iodine transporter mediates the transport of iodide into the thyroid as the first step in thyroid hormone synthesis. Antibodies to the iodine transporter occur in a few patients and may have a role in hypothyroidism.

Many thyroid autoantibodies can fix complement. As a result complement dependent antibody mediated cytotoxicity may contribute to destruction of thyroid tissue in patients with Hashimoto thyroiditis. The importance of this action, however in comparision with the T cell ? mediated effects is uncertain.

Apoptosis mediated by the Fas-FasL system has also been implicated in the pathogenesis of Hashimoto thyroiditis. FasL is constitutively expressed by both normal and Hashimoto thyroid epithelial cells. Interleukin IL-1? is abundant in Hashimoto glands and induces the expression of Fas on the cells; This triggers Fas-FasL interactions among the thyroid epithelial cells and activates the apoptotic cell death program.