Thyroid stimulating immunoglobulin concentration is associated with disease activity and predicts response to treatment with intravenous methylprednisolone in patients with Graves' orbitopathy

Front Endocrinol (Lausanne). 2024 Mar 21:15:1340415. doi: 10.3389/fendo.2024.1340415. eCollection 2024.

Abstract

Background: Thyroid stimulating immunoglobulins (TSI) play a central role in the pathogenesis of Graves' orbitopathy (GO), while soluble interleukin-2 receptor (sIL-2R) is a marker for T-cell activity. We investigated TSI and sIL-2R levels in relation to thyroid function, disease activity and severity and response to treatment with intravenous methylprednisolone (IVMP) in patients with GO.

Methods: TSI (bridge-based TSI binding assay), sIL-2R, TSH and fT4 levels were measured in biobank serum samples from 111 GO patients (37 male, 74 female; mean age 49.2 years old) and 25 healthy controls (5 male, 20 female; mean age 39.8 years old). Clinical characteristics and response to treatment were retrospectively retrieved from patient files.

Results: Higher sIL-2R levels were observed in GO patients compared to controls (p < 0.001). sIL-2R correlated with fT4 (r = 0.26), TSH (r = -0.40) and TSI (r = 0.21). TSI and sIL-2R concentrations were higher in patients with active compared to inactive GO (p < 0.001 and p < 0.05, respectively). Both TSI and sIL-2R correlated with total clinical activity score (CAS; r = 0.33 and r = 0.28, respectively) and with several individual CAS items. Cut-off levels for predicting active GO were 2.62 IU/L for TSI (AUC = 0.71, sensitivity 69%, specificity 69%) and 428 IU/mL for sIL-2R (AUC = 0.64, sensitivity 62%, specificity 62%). In multivariate testing higher TSI (p < 0.01), higher age (p < 0.001) and longer disease duration (p < 0.01) were associated with disease activity. TSI levels were higher in patients with a poor IVMP response (p = 0.048), while sIL-2R levels did not differ between responders and non-responders. TSI cut-off for predicting IVMP response was 19.4 IU/L (AUC = 0.69, sensitivity 50%, specificity 91%). In multivariate analysis TSI was the only independent predictor of response to IVMP (p < 0.05).

Conclusions: High TSI levels are associated with active disease (cut-off 2.62 IU/L) and predict poor response to IVMP treatment (cut-off 19.4 IU/L) in GO. While sIL-2R correlates with disease activity, it is also related to thyroid function, making it less useful as an additional biomarker in GO.

Keywords: TSI; disease activity; graves’ orbitopathy; methylprednisolone; sIL-2R; treatment response.

MeSH terms

  • Adult
  • Female
  • Graves Ophthalmopathy* / drug therapy
  • Humans
  • Immunoglobulins, Thyroid-Stimulating
  • Male
  • Middle Aged
  • Receptors, Thyrotropin
  • Retrospective Studies
  • Thyrotropin

Substances

  • Immunoglobulins, Thyroid-Stimulating
  • Receptors, Thyrotropin
  • Thyrotropin

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the following foundations: ZonMw, Stichting Wetenschappelijk Onderzoek Oogziekenhuis (SWOO-Flieringa), Rotterdamse Stichting voor Blindenbelangen (RSB), Stichting Ooglijders, Oogfonds (UitZicht) and Foundation Combined Ophthalmic Research Rotterdam (CORR). The funding organizations had no role in the design or conduct of this research. They provided unrestricted grants.