Relevance of TSH-Receptor stimulating and blocking autoantibody measurement for the prediction of relapse in Graves' disease

Abstract

Recently, we demonstrated that higher levels of autoantibodies to the human TSH-Receptor (TRAK human) predict relapse of hyperthyroidism in Graves' disease (GD). The aim of this study was to extend this outcome prediction with the help of stimulating (TSAb) and blocking (TBAb) TSH receptor autoantibody measurement. Altogether, 89 patients (79 female, 10 male) were retrospectively analyzed, of whom 64 patients (72%) did not go into remission or relapsed, whereas 25 patients (28%) went into remission (median follow-up: 20,1 months). TSAb and TBAb measurement was performed in a CHO cell assay with cAMP readout at the time of their first visit in our outpatient clinic (single point measurement in median 4,4 months after initial diagnosis). Within the remission group 19/26 patients (73%) were TSAb positive, whereas in the relapse group 53/64 patients (83%) revealed TSAb positivity. The mean stimulation indices (SI) were 4,3 and 12,8 in the relapse and remission group, respectively (p=0,015). By using a threshold of 10 SI, the specificity for relapse was 96,0%, as only 1 of 20 patients with an SI above 10 went into remission during follow-up (PPV 95%). Most TSAb positive patients had also high levels of TBII. Both groups showed no difference with respect to blocking type autoantibodies. Most GD patients in both groups were negative for TBAb, and only 1/26 patients in the remission group and 6 of 64 patients who relapsed showed weak TBAb activity (between 30–40% inhibition). In summary, high TSAb levels (like high TBII levels) are useful for the prediction of relapse in GD patients. In contrast, TBAb measurement does not add any valuable information in this context. In the clinical routine TSAb/TBAb measurement does not play an important role for diagnosis or outcome prediction of GD, since the human TBII assay is easier to perform and offers similar, if not better information. Bioassays should be reserved for special clinical questions (e.g. Graves' disease in pregnancy).