Diagnostic discordance and performance of third-generation competitive TRAb vs. sandwich TSI ELISA in the diagnosis of Graves’ disease

BACKGROUND: Autoantibodies against the TSH receptor (TRAb) mediate hyperthyroidism in Graves' disease (GD). While 3rd-generation competitive immunoassays are the standard screening tool, the performance of accessible, sandwich ELISA-based TSI remains understudied in specific populations. This study evaluated the diagnostic utility of a sandwich TSI ELISA compared to a competitive TRAb ELISA in Iraqi patients with untreated hyperthyroidism. METHODS: A case-control study on 60 newly diagnosed, untreated GD patients and 30 age-matched healthy controls. Serum samples were analyzed using a competitive inhibition ELISA for TRAb and a double-antigen sandwich ELISA for TSI. Clinical severity and disease duration were compared between concordant and discordant groups. RESULTS: = 0.053). CONCLUSION: The competitive TRAb ELISA significantly outperformed the sandwich TSI ELISA. The observed discordance does not seem to be related to disease severity. We hypothesize that this discordance may result from the sandwich assay's limited ability to detect low-affinity or polyclonal antibodies, which are often present in early Graves' disease. Thus, the competitive TRAb assay remains the more robust and reliable primary screening tool.