The hyperthyroidism of Graves' disease is caused by thyrotropin receptor autoantibodies. These antibodies mimic the TSH that normally binds to the receptor and stimulate the thyroid to produce thyroid hormone. These antibodies are generally detected by two types of assays. One type of assay measures the ability of IgG to inhibit binding of TSH to solubilized TSH receptor in an enzyme immunoassay format (TRAb or TBII). The other type of assay is more of a bioassay in that it measures the ability of the patient's IgG (or serum) to stimulate cAMP production in tissue cultures of various kinds. It is clear from the literature that the solublized receptor binding assays are not clinically interchangable with the functional bioassays because the populations of antibodies measured by each assay are not completely concordant. This results, in part, due to the fact that not all TSH receptor binding immunoglobulins are stimulatory. Some of the receptor binding antibodies are inhibitory and have been implicated in cases of Hashimoto thyroiditis.

The nomenclature used in the literature for the various TSH receptor assays is inconsistent and confusing. Assays that measure binding of TSH to solubilized receptor are often referred to as TRAb (thyroid receptor antibody), TBII (TSH-binding inhibitor immunoglobulin) or LATS (long-acting thyroid stimulator) assays. Assays that measure the ability of IgG to bind to TSH receptor on cells and stimulate adenylate cyclase production have generally been referred to as TSI (thyroid-stimulating immunoglobulin) assays. Traditional TSI assays have used either a rat thyroid cell line, FRTL-5, or a Chinese hamster ovary (CHO) cell line transfected with the human TSH receptor.  TSH receptor binding immunoglobulin in the patient sample is allowed to bind to the receptors on the cell surfaces in these cultures. The TSH receptor mediates its function through the production of cyclic AMP within the cell cytosol. An immunoassay is used to measure the increases in cyclic AMP concentration that results from adding the patient immunoglobulin to the cells in culture. These assays have been reported to have sensitivities of about 80% but concordance of only 70%.

References:

1. thyroid tests Practice Guidelines, National Academy of Clinical Biochemistry (NACB), USA.