High TRAb Titer at Diagnosis Predicts Persistent Positivity and Relapse in Graves’ Disease after Prolonged Antithyroid Therapy

The association between high thyrotropin receptor antibody (TRAb) titers at diagnosis and long-term outcomes following prolonged antithyroid drug (ATD) therapy in Graves' disease (GD) remains unclear. This study examined TRAb dynamics and outcomes in high-titer patients receiving prolonged ATD. In this retrospective cohort (2018-2021), 1,148 of 3,052 newly diagnosed GD patients met inclusion criteria (≥18-month ATD course, TRAb negativity before withdrawal, and ≥12-month follow-up). Initial TRAb levels were defined as low-titer (<5.25 IU/L, 3×upper normal limit [UNL]), intermediate-titer (5.25-10.5 IU/L), and high-titer (>10.5 IU/L, 6×UNL). Outcomes included TRAb dynamics, treatment duration, and relapse. High-titer patients required longer therapy (50 months vs. 30 months vs. 22 months, P<0.001) and slower thyroid-stimulating hormone normalization (6 months vs. 4 months vs. 2 months, both P<0.001). TRAb negativity at 24/48 months occurred in 91.85%/99.26% (low-titer), 52.38%/75.24% (intermediate-titer), and 12.70%/52.68% (high-titer) (P<0.001). High-titer patients showed fluctuant (46.20%) or smoldering (28.89%) trends. Remission rates declined with higher TRAb titer (60.45% vs. 42.70% vs. 30.47%, P<0.001). High-titer patients showed increased risk of persistent TRAb positivity (2.17-fold; 95% confidence interval [CI], 1.55 to 3.05) and relapse (1.66-fold; 95% CI, 1.45 to 3.22). Thresholds of 10.90 IU/L and 16.01 IU/L predicted positivity and relapse, respectively. Definitive therapy post-relapse was more common in high-titer patients (38.29% vs. 16.98% in low-titer, P<0.001). High TRAb titers strongly predict persistent TRAb positivity and relapse after ATD withdrawal. Cut-off at 10.90 and 16.01 IU/L may guide prognosis and treatment.