Clinical Applications of TSH Receptor Antibodies in Thyroid Diseases

Abstract

The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR), combined with advances in molecular techniques, have facilitated the understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR at the molecular level and have allowed the delineation of their clinical role. TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the blocking TSHRAbs cause hypothyroidism in some patients with autoimmune hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring TSHRAbs has potential clinical implications in differential diagnosis of Graves' disease, predicting the outcome of Graves' disease after antithyroid drug treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of stimulating TSHRAbs with epitopes other than on the N-terminal region of the extracellular domain, is significantly associated with favorable long-term clinical response to antithyroid drug treatment. Measuring these subtypes for thyroid-stimulating antibody (TSAb) has potential clinical implications, for example, in predicting responsiveness to treatment in untreated patients with Graves' disease.

A Novel Bioreporter Assay for Thyrotropin Receptor Antibodies Using a Chimeric Thyrotropin Receptor (Mc4) Is More Useful in Differentiation of Graves' Disease from Painless Thyroiditis Than Conventional Thyrotropin-Stimulating Antibody Assay Using Porcine Thyroid Cells

“…G raves' disease (GD) is an autoimmune thyroid disease caused by anti-thyrotropin (TSH) receptor autoantibody called TSH receptor antibodies (TSHRAbs) (1)(2)(3)(4)(5)(6). TSHRAbs in patient's sera have been clinically used in the differential diagnosis of GD or in monitoring of GD patients during treatment with antithyroid drugs (ATD) (7,8).…”

Measurement of thyroid stimulating immunoglobulins using a novel thyroid stimulating hormone receptor–guanine nucleotide-binding protein, (GNAS) fusion bioassay

“…Autoantibodies to the TSHR (TSH receptor antibody: TRAb) may be stimulating, blocking or neutral [5]. Stimulating antibodies mimic the action of thyroid stimulating hormone (TSH) and cause hyperthyroidism (Graves' disease), whereas blocking antibodies block the binding of TSH and cause hypothyroidism [5][6][7]. Both stimulating and blocking antibodies can occur together in any given patient and may change over time [3,8,9].…”

“…Several different assays are used to measure TRAb [7], including functional cell-based bioassays [10]. In these assays, cells expressing the TSHR on their plasma membrane are incubated with test serum and any resultant stimulation of the G-protein coupled receptor (GPCR) pathway is measured by directly measuring the pathway second messenger, cyclic AMP (cAMP), or indirectly using a cAMP responsive promoter element driving a reporter gene.…”

Thyrotropin Receptor Antibody Assays

“…2,3 The diagnosis is easily confirmed in most patients with a low thyroid-stimulating hormone (TSH) concentration and an elevated FT4 concentration. In early Graves disease, if T4 levels are normal the measurement of T3 is useful.…”