binding to residues 261-370 or 388-403 block the activity. TRAbs are present in 70-100% of Graves' disease (85-100% for activating antibodies and 75-96% for blocking antibodies) and 1-2% of normal individuals. Activating TRAbs are characteristic of Graves' disease (autoimmune hyperthyroidism). TPO antibody is measured more easily than the TSH receptor antibody, and so is often used as a surrogate in the diagnosis of Graves' disease. These antibodies activate adenylate cyclase by binding to the TSH receptor. This causes the production of thyroid hormones and subsequent growth and vascularisation of the thyroid. TRAbs are also useful in the diagnosis of Graves' ophthalmopathy. Although the exact mechanism of how TRAbs induce Graves' ophthalmopathy is unknown, it is likely that the antibodies bind to TSH receptors in retro-orbital tissues, causing infiltration of lymphocytes. This inflammatory response leads to cytokine production that causes fibroblasts to produce glycosaminoglycans, leading to ophthalmopathy. Blocking TRAbs (also known as thyrotropin binding inhibitory immunoglobulins (TBII)) competitively block the activity of TSH on the receptor. This can cause hypothyroidism by reducing the thyrotropic effects of TSH. They are found in Hashimoto's thyroiditis and Graves' disease and may be cause of fluctuation of thyroid function in the latter. During treatment of Graves' disease they may also become the predominant antibody, which can cause hypothyroidism. The clinical and physiological relevance of neutral antibodies remains unclear. However, they may be involved in prolonging the TSH receptor half-life. Thyroglobulin (TG) antibodies Thyroglobulin antibodies are specific for thyroglobulin, a 660kDa matrix protein involved in the process of thyroid hormone production. They are found in 70% of Hashimoto's thyroiditis, 60% of idiopathic hypothyroidism, 30% of Graves' disease, a small proportion of thyroid carcinoma and 3% of normal individuals. Anti-TPO antibodies are present in 99% of cases where thyroglobulin antibodies are present, however only 35% of anti-TPO antibody positive cases also demonstrate thyroglobulin antibodies. Anti–Na+/ I− symporter Anti-Na+/I− symporter antibodies are a more recent discovery of possible thyroid autoantibodies and their role in thyroid disease remains uncertain. They are present in approximately 20% of Graves' disease and 24% of Hashimoto's thyroiditis. Pathogenesis The production of antibodies in Graves' disease is thought to arise by activation of CD4+ T-cells, followed by B-cell recruitment into the thyroid. These B-cells produce antibodies specific to the thyroid antigens. In Hashimoto's thyroiditis, activated CD4+ T-cells produce interferon-γ, causing the thyroid cells to display MHC class II molecules. This expands the autoreactive T-cell