TRAb are autoantibodies and as such, they are not a molecularly defined analyte but a mixture of high-affinity IgG that bind selected epitopes of the TSH-R that varies among individuals and fluctuates within one individual. Small changes in the level, affinity, or fine specificity of the TRAb can result in major changes in their capacity to activate the TSH-R. Measuring TRAbs is, therefore, challenging, and generations of tests using different TSH-R preparations and ligands have been developed over the years, while in parallel, labeling and detection methods have also improved for the immunoassays in general. Therefore, the number of reports comparing tests in terms of sensitivity, specificity, safety, and cost-effectiveness as applied to different populations, have grown over the years [
19–
25] reflecting that none of them have yet met all the expectations of the clinical endocrinologist.