Clinical Summary

Toxic diffuse goiter, also known as Graves’ disease (GD), is an autoimmune disorder and the most common cause of hyperthyroidism. In GD, thyroid stimulating immunoglobulins (TSI) bind to the TSH receptor (TSHR) and mimic TSH stimulation of the thyroid gland.1 Because TSI induced thyroid hormone secretion is not controlled by negative feedback, such stimulation leads to GD hyperthyroidism.2 The TSH receptor contains a large extracellular domain that presents epitopes for a variety of autoantibodies, including TSI and Thyroid Blocking Immunoglobulins (TBI).3 In contrast to TSI, TBI bind to the TSH receptor and inhibit TSH stimulation of thyroid cells, leading to hypothyroidism.4,5 TSHR autoantibody (TRAb) assays do not distinguish between TSI and TBI.6-8 The IMMULITE 2000 TSI assay utilizes recombinant human TSH receptors (hTSHR) for the specific detection of thyroid stimulating autoantibodies. The clinical utility of TSI measurement includes a determination of the autoimmune etiology of thyrotoxicosis,9 monitoring Graves’ patient therapy,10 prediction of remission or relapse,11 confirmation of Graves’ ophthalmopathy,12 and prediction of hyperthyroidism in neonates.