# Pediatric Graves’ orbitopathy: TRAb and FT-3 are also prognostic factors in children—A tertiary center study

**Authors:** Karim Al-Ghazzawi, Michael Oeverhaus, Arber Rama, Cordula Kiewert, Nikolaos Bechrakis, Ying Chen, Inga Neumann, Anja Eckstein

PMC · DOI: 10.1186/s13044-026-00286-7 · 2026-01-22

## TL;DR

This study finds that FT-3 and TRAb levels predict remission in children with Graves’ orbitopathy, suggesting thyroidectomy may benefit those with high levels.

## Contribution

The study identifies FT-3 and TRAb as novel prognostic factors in pediatric Graves’ orbitopathy and suggests thyroidectomy improves outcomes in high-risk patients.

## Key findings

- Pediatric Graves’ orbitopathy typically presents with milder symptoms than adult cases.
- High FT-3 or TRAb levels at diagnosis are linked to lower remission rates in children.
- Thyroidectomy leads to faster TRAb normalization and higher remission rates in pediatric patients.

## Abstract

Graves’ orbitopathy (GO) is an autoimmune disease of the orbit that occurs most often in relation to autoimmune. The clinical picture varies and is dependent on many risk factors, especially age, antibody levels and the quality of control of thyroid function. This study aimed to (1) compare the clinical characteristics of pediatric and adult Graves’ orbitopathy (GO), (2) identify factors associated with remission in pediatric GO, and (3) assess the influence of thyroid treatment modality on TRAb dynamics in pediatric patients.

We reviewed the medical records of all pediatric patients with GO (< 18 years) and compared the results with those of a random sample of 482 (18–50 years old) adult patients from the Graves’ Orbitopathy Database (GODE), which includes 4260 patients from our tertiary referral center. A subcohort analysis of pediatric GO patients receiving definitive (surgical) thyroid or medical thyroid treatment was conducted. Risk stratification for remission in pediatric GO patients with the help of univariate as well as multiple logistic regression for different variables, including the serological laboratory results of Free Triiodothyronine (FT-3), Free Thyroxine (FT-4), TSH-receptor autoantibodies (TRAb) and antithyroglobulin antibodies (anti-TG), was conducted. Only those with complete data sets were included in the statistical analysis.

Clinical presentation varied significantly between pediatric and adult patients, with children showing mostly mild manifestations (81% vs. 48.7%, p < 0.0001), resulting in a much lower need for anti-inflammatory treatments and rehabilitative surgery. Univariate analyses revealed a significantly decreased probability of remission in nonthyroidectomized pediatric GO patients with high FT-3 or TRAb levels at the first clinical presentation (p < 0.05). The surgically managed pediatric GO cohort had higher initial TRAb levels but quicker TRAb normalization over time and higher serological remission rates (TRAb < 1,75UI) (38% vs 74%, respectively) than did the nonthyroidectomized pediatric subgroup at the last clinical presentation. Interestingly, pediatric GO patients in whom antithyroid drug (ATD) therapy was initiated only at or after their first clinical visit at our referral center presented greater clinical activity and prolonged TRAb normalization duration than patients who were already receiving anti-thyroid drugs did (p < 0.005).

FT-3 and TRAb levels are also prognostic factors for remission in pediatric patients with GO. International guidelines for the management of pediatric GO have divided opinions on the duration of anti-thyroid drugs prior to definitive surgical thyroid therapy (2–5 years). Our results highlight the prognostic role of serum biomarkers (FT-3, FT-4, TSH-receptor autoantibodies (TRAb)) at first clinical presentation and hint to positive effects of thyroidectomy in pediatric GO patients with high FT-3 or TRAb and therefore unlikely remission in the conservative treated subpopulation.

The online version contains supplementary material available at 10.1186/s13044-026-00286-7.

## Linked entities

- **Diseases:** Graves’ orbitopathy (MONDO:0001509)

## Full-text entities

- **Genes:** CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, TG (thyroglobulin) [NCBI Gene 7038] {aka AITD3, TGN}, TSHR (thyroid stimulating hormone receptor) [NCBI Gene 7253] {aka CHNG1, LGR3, hTSHR-I}, TPO (thyroid peroxidase) [NCBI Gene 7173] {aka MSA, TDH2A, TPX}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}
- **Diseases:** GD (MESH:D006111), eye disease (MESH:D005128), painful eye movement (MESH:D058447), autoimmune thyroid disease (MESH:D013967), myasthenia gravis (MESH:D009157), thyroid disease (MESH:D013959), Diplopia (MESH:D004172), lid redness (MESH:D004409), autoimmune conditions (MESH:D001327), hypocalcemia (MESH:D006996), eyelid (MESH:D005141), swelling of the caruncle or placenta (MESH:D010922), Graves' hyperthyroidism (MESH:D006980), STS (MESH:D017695), ATD (MESH:D000081015), strabismus (MESH:D013285), DON (MESH:D009901), lid retraction (MESH:D004370), hypoparathyroidism (MESH:D007011), inflammation (MESH:D007249), GO (MESH:D049970), retrobulbar pain (MESH:D010146), compressive neuropathy (MESH:D009408), Proptosis (MESH:D005094), lid edema (MESH:D004487), autoimmune disease of the orbit (MESH:D009916), recurrent laryngeal nerve injury (MESH:D061226), Motility dysfunction (MESH:D015835)
- **Chemicals:** Triiodothyronine (MESH:D014284), Thyroxine (MESH:D013974), FT4 (-), methimazole (MESH:D008713), ruthenium (MESH:D012428), Radioiodine (MESH:C000614965), iodine (MESH:D007455), ICG (MESH:D007208), hyaluronic acid (MESH:D006820), propylthiouracil (MESH:D011441), steroid (MESH:D013256), FT (MESH:D005641)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12828925/full.md

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Source: https://tomesphere.com/paper/PMC12828925