MON-351 - Higher Baseline Thyroid Stimulating Immunoglobulin and Biochemical Severity Predict Non-Remission in A USA Pediatric Graves' Disease Cohort, While Thyroid Peroxidase and Thyroglobulin Antibodies' Titers Are Not Predictive

Background
Remission after antithyroid therapy in pediatric Graves’ disease (GD) is variable. Most pediatric prognostic studies emphasize binding thyrotropin receptor antibody (TRAb) assays, which quantify receptor binding immunoglobulins that may include both stimulating and blocking activity. Thyroid stimulating immunoglobulin (TSI) is a functional measure of stimulating activity and may therefore provide more specific prognostic information. In addition, while thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) are markers of risk for autoimmune thyroid injury, their prognostic value particularly when evaluated as baseline titers remains uncertain.

Objective
To compare baseline TSI versus TRAb as predictors of remission in children with GD treated with methimazole (MMI) and to evaluate whether baseline TPOAb and TgAb titers predict remission.

Methods
Retrospective cohort study of children >2 years of age with GD treated with MMI at Nationwide Children’s Hospital (July 2015–June 2025). Of 314 screened, we excluded patients who underwent definitive therapy, had trisomy 21, or had another autoimmune disease, leaving 108 for analysis. Remission was defined as being off MMI for ≥12 months without relapse. We collected demographics and baseline clinical features at diagnosis, baseline thyroid function tests (TSH, free T4, total T3), and initial and current MMI dose. Thyroid antibody titers (TSI, TRAb, TPOAb, TgAb) at baseline and when available 2 years after diagnosis. Baseline variables were compared between remission and non-remission groups. Non-normally distributed data are reported as median (IQR) and compared using Mann–Whitney U; categorical variables were compared using chi-square.

Results
Among 108 patients (53 remission; 55 non-remission), baseline TSI was higher in non-remission versus remission (6.8 vs 4.19, p 0.019), whereas baseline TRAb demonstrated only a trend toward higher values in non-remission (9.25 vs 7.0, p 0.059). Non remission was also associated with greater biochemical severity at diagnosis, including higher total T3 (530 vs 404.5, p 0.026) and higher initial MMI dose (0.40 vs 0.35 mg/kg/day, p=0.037). In contrast, baseline TPOAb and TgAb titers were not associated with remission (p 0.860 and p 0.438, respectively).

Conclusions
Baseline TSI showed a stronger association with non-remission than TRAb, supporting the clinical relevance of measuring stimulating antibody activity for early risk stratification. Higher total T3 and higher MMI dose were also associated with non-remission. Baseline TPOAb and TgAb titers were non predictive despite a biologic rationale linking these antibodies to autoimmune thyroid injury. Together, these findings support the use of baseline TSI and biochemical severity at presentation to stratify remission likelihood and guide counseling in pediatric patients.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*