The prognostic role of TPO antibodies in Graves’ hyperthyroidism: a systematic review

OBJECTIVE: Graves' disease (GD) is the leading global cause of hyperthyroidism. Despite their frequent presence, the clinical relevance of thyroid peroxidase antibodies (TPOAb) in GD remains unclear. This systematic review evaluates the prognostic value of TPOAb in GD, including associations between baseline TPOAb status, longitudinal titre changes, and treatment outcomes. METHODS: PubMed and Embase were systematically searched in February 2026 for English-language studies of GD patients treated with antithyroid drugs (ATD), radioactive iodine (RAI), or thyroidectomy, reporting TPOAb measurements at least at diagnosis. Studies were grouped into those comparing TPOAb-positive and TPOAb-negative patients regarding baseline disease characteristics and treatment response, and those analysing longitudinal TPOAb titre changes in relation to treatment outcomes. RESULTS: Fifteen studies (N=36-469 patients/study) were included. TPOAb positivity at diagnosis showed inconsistent associations with baseline disease characteristics and did not predict remission, relapse or hypothyroidism after ATD, but was associated with a higher incidence of hypothyroidism following RAI. While TPOAb titre changes were not consistently associated with relapse, increasing TPOAb levels during ATD treatment may be linked to a higher risk of late hypothyroidism, and rising titres after RAI to an increased risk of early hypothyroidism. No thyroidectomy studies met the inclusion criteria. CONCLUSION: TPOAb status at diagnosis does not consistently predict disease severity at diagnosis or ATD outcomes in GD; therefore routine measurement is not supported. Limited evidence suggests that baseline TPOAb and early post-RAI changes may help predict hypothyroidism after RAI. Overall, the clinical role of TPOAb in GD remains uncertain and warrants further research.