The role of thyrotrophin receptor antibody assays in graves' disease

Thyrotrophin receptor antibodies (TRAb) exist as stimulating or blocking antibodies in the serum (neutral TRAb have been identified recently). The clinical features of GD occur when stimulating TRAb predominate. But the relationship of TRAb to clinical phenotype and outcome is not clear when current assay methods are used. Therefore no consensus exists about its utility in diagnosing and predicting outcome in GD. The most commonly used TRAb assays, measure thyroid binding inhibiting immunoglobulins (TBII or "receptor assays") and don't differentiate between stimulating and blocking antibodies. However, the more expensive, technically demanding and less freely available "biological assays" differentiate between them by their ability to stimulate cyclic AMP or failure to do so. Failure to differentiate between TRAb types and its heterogeneous molecular and functional properties has limited TBII use to GD diagnosis and differentiating from other forms of thyrotoxicosis. The current 2nd-3rd generation receptor assays are highly sensitive and specific when used for this purpose. TRAb assays should also be done in appropriate pregnant women. Current data do not support its use in outcome prediction as there is a significant variability of assay methodology, population characteristics and study design in published data, resulting in a lack of consensus.