Autoimmune Thyroid Disease

Abstract

Autoimmune thyroid disease is common and was the first autoimmune disease to be described, based on observations in animals immunized with thyroid extract and adjuvant. There are several different clinical presentations which, although being distinctive, share some common features in terms of genetic susceptibility, environmental factors that predispose to disease and pathogenic features such as the presence of autoantibodies against thyroglobulin and thyroid peroxidase. In autoimmune hypothyroidism, the thyroid is initially enlarged due to the presence of a marked lymphocytic infiltrate; this phase is followed by fibrosis, atrophy of the gland, and failure to synthesize normal levels of thyroid hormones. The main etiological factors in this process are cytotoxic T cells and an intrathyroidal proinflammatory state created by local cytokine release. Humoral autoimmunity may contribute through the action of thyroid-stimulating hormone (TSH) receptor-blocking autoantibodies or through the activation of complement and antibody-dependent NK cell-mediated cytotoxicity. In Graves' disease, thyroid overactivity is caused by autoantibodies which stimulate the TSH receptor. T cells which recognize the receptor also localize to the orbit in many of these patients, as a subpopulation of fibroblasts at this location also express the receptor; the cytokines produced by these T cells in turn leads to the clinical features of Graves' ophthalmopathy.