Clinical Information

Autoimmune thyroid disease is characterized by the presence of autoantibodies against various thyroid components, namely the thyrotropin receptor, thyroid peroxidase, and thyroglobulin, as well as by an inflammatory cellular infiltrate of variable severity within the gland.

Among the autoantibodies found in autoimmune thyroid disease, thyrotropin receptor autoantibodies (TRAb) are most closely associated with disease pathogenesis. All forms of autoimmune thyrotoxicosis (Graves disease [GD], Hashitoxicosis, neonatal thyrotoxicosis) are caused by the production of stimulating TRAb. These autoantibodies, also known as long-acting-thyroid-stimulators or thyroid-stimulating immunoglobulins (TSI), bind to the receptor and transactivate it, leading to stimulation of the thyroid gland independent of the normal feedback-regulated thyrotropin stimulation.

Some patients with GD also have TRAb that do not transactivate the thyrotropin receptor. The balance between stimulating and blocking antibodies, as well as their individual titers, is felt to be a determinant of GD severity. Some patients with autoimmune hypothyroidism also have evidence of either blocking TRAb or, rarely, TSI.

Thyrotropin receptor autoantibodies may be detected before autoimmune thyrotoxicosis becomes biochemically or clinically manifest. Since none of the treatments for GD are aimed at the underlying disease process but rather ablate thyroid tissue or block thyroid hormone synthesis, TSI may persist after apparent clinical cure. This is of particular relevance for pregnant women with a history of GD treated with thyroid-ablative therapy. Some of these women may continue to produce TSI. Since TSI are IgG antibodies, they can cross the placental barrier causing neonatal thyrotoxicosis.

While the gold standard for thyroid-stimulating immunoglobulins is the bioassay (see TSI / Thyroid-Stimulating Immunoglobulin, Serum), the TRAb test has a shorter turnaround time, less analytical variability, and is less expensive.