Thyrotropin (TSH) Receptor Antibodies (TRAb)

The Thyrotropin (TSH) Receptor Antibodies (TRAb) assay—also known as thyroid-stimulating immunoglobulins (TSI) or TSH-binding inhibitory immunoglobulins (TBII)—is used to confirm Graves disease and to distinguish antibody-mediated thyrotoxicosis from other etiologies of hyperthyroidism. It is also applied when blocking antibody–mediated hypothyroidism is suspected. Serial TRAb measurements are used to assess disease activity, inform prognosis including the likelihood of relapse, and monitor response to antithyroid drug therapy. During pregnancy, when radionuclide procedures are avoided, TRAb testing supports evaluation of patients with current or prior Graves disease and helps estimate the risk of neonatal thyroid dysfunction.

TSH receptor antibodies are a heterogeneous group of predominantly IgG autoantibodies that bind the TSH receptor. Some are stimulating and drive thyroid hormone overproduction with diffuse goiter and hyperthyroidism, while others are blocking and impair receptor signaling, resulting in hypothyroidism. These antibodies are a direct pathogenic mechanism in Graves disease and may also be present in autoimmune thyroiditis. Stimulating antibodies (often termed thyroid-stimulating immunoglobulins) are detected in approximately 85% to 100% of patients with Graves disease, and titers correlate with overall disease activity and the severity of thyroid-associated ophthalmopathy. Concentrations generally fall with effective antithyroid therapy, and longitudinal measurement can assist in management decisions and in estimating the probability of relapse following treatment. TRAb cross the placenta and can produce neonatal thyrotoxicosis; blocking antibodies can lead to transient neonatal hypothyroidism. In pregnancy, TRAb assessment provides a nonradioactive alternative to thyroid scintigraphy. TRAb are not fully specific for Graves disease and can be found in a subset of individuals with Hashimoto thyroiditis.