TSH-receptor autoantibodies: pathophysiology, assay methods, and clinical applications

TSH receptor antibodies (TRAbs) are characteristic indicators for the common autoimmune thyroid disease Graves disease (GD). In almost all patients stimulating TRAbs are found leading to hyperthyroidism as these antibodies act in an agonistic manner to TSH. Besides stimulating TRAbs, other TRAbs are also frequently found leading to inhibition of TSH receptor signaling (blocking TRAbs) or to the activation of different signaling cascades resulting in e.g. thyrocyte apoptosis (cleavage antibodies). Patients' sera may contain all three types of TRAbs. Dependent on the activity of these particular TSHR autoantibodies clinical symptoms might change. Within this review we summarize current genetic and environmental factors that are generally accepted for GD's etiology. Binding sides to the TSH receptor as well as the resulting signaling cascades are described just as the current used assay methods for TRAb measurement. Finally, we illustrate the clinical impact of TRAbs in the follow-up of GD patients with special focus on GD patients suffering from Graves' ophthalmopathy.