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The phenotype of Graves’ orbitopathy is associated with thyrotropin receptor antibody levels

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Abstract

Purpose

Graves’ orbitopathy (GO) is a specific inflammatory disorder of the orbit characterized by a highly heterogeneous clinical phenotype. The role of thyrotropin receptor antibodies (TSH-R-Ab) has been widely researched, however there is still no evidence that these antibodies have a direct pathogenic role in this pathology. The aim of this study was to examine their relation to the individual clinical features of GO.

Methods

Ninety-one consecutive patients with GO were recruited. Total antibody concentration (TSH-R binding inhibitory immunoglobulins, TBII) and their functional activity (stimulating TSH-R-Ab, TSAb) were measured using binding immunoassay and cell-based bioassay, respectively.

Results

Both TSAb and TBII levels were significantly associated to the clinical parameters of GO activity. TSAb was a more sensitive serological marker compared to TBII pertaining to eyelid retraction and edema, proptosis, extra-orbital muscle disorders, diplopia, irritable eye symptoms, and photophobia. TSAb, but not TBII, was a significant predictive marker of conjunctival redness, chemosis, caruncle/plica inflammation, eye irritation, and orbital pain, (odds ratio: 3.096, p = 0.016; 5.833, p = 0.009; 6.443, p = 0.020; 3.167, p = 0.045; 2.893, p = 0.032; versus 2.187, p = 0.093; 2.775, p = 0.081; 3.824, p = 0.055; 0.952, p = 0.930; 2.226, p = 0.099, respectively). Neither TSAb nor TBII correlated with the level of proptosis (ρ = 0.259, p = 0.090, and ρ = 0.254, p = 0.104, respectively), however rising TSAb levels were strongly associated to the level of proptosis.

Conclusions

TSH-R-Ab were significantly associated with GO’s phenotype. Especially TSAb, as a sensitive and predictive serological biomarker, can improve diagnosis and management of GO.

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Availability of data and materials

The data accompanying the results of this study are available upon request from the corresponding author.

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Funding

This study was funded by a Grant No. 175036 of the Ministry of Education, Science and Technological Development, Republic of Serbia, and through Grant Agreement with the Faculty of Pharmacy, University of Belgrade No. 451-03-9/2021-14/200161. The JGU Medical Center receives research-associated funding from and GJK consults for Quidelortho, USA.

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Author notes

  1. Marija Sarić Matutinović and George J. Kahaly share first authorship.

Authors and Affiliations

  1. Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

    M. Sarić Matutinović & S. Ignjatović

  2. Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University [JGU] Medical Center, Mainz, Germany

    G. J. Kahaly

  3. Clinic of Endocrinology, University Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia

    M. Žarković, J. Ćirić & B. Nedeljković Beleslin

Authors
  1. M. Sarić Matutinović
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  2. G. J. Kahaly
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  3. M. Žarković
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  4. J. Ćirić
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  5. S. Ignjatović
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  6. B. Nedeljković Beleslin
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Contributions

SMM: concept/design, data collection, laboratory analysis, statistics, writing- and original draft preparation; GJK laboratory analysis, interpretation, writing, editing, critical review, and approval of the article; ŽM: design, critical review and editing; ĆJ: data collection, critical review; IS: concept/design, critical review, approval of the article; NBB: concept/design, data collection, interpretation, critical review, final approval.

Corresponding author

Correspondence to M. Sarić Matutinović.

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Conflict of interests

The JGU Medical Center receives research-associated funding from GJK and GJK consults for Quidelortho, USA. MŽ is a member of the editorial board of the Journal of the Endocrinological Investigation. MSM, JĆ, SI and BNB have nothing to disclose.

Ethics approval

All patients signed an informed consent upon admission and Ethics Committee approval (944/3: 17.06.2019.) was obtained prior to the study. Principles of good clinical and laboratory practice, the Declaration of Helsinki, and applicable national and institutional regulations were followed during this study.

Informed consent

All patients signed an informed consent upon admission and Ethics Committee approval (944/3: 17.06.2019.) was obtained prior to the study. Principles of good clinical and laboratory practice, the Declaration of Helsinki, and applicable national and institutional regulations were followed during this study.

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Sarić Matutinović, M., Kahaly, G.J., Žarković, M. et al. The phenotype of Graves’ orbitopathy is associated with thyrotropin receptor antibody levels. J Endocrinol Invest 46, 2309–2317 (2023). https://doi.org/10.1007/s40618-023-02085-5

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  • DOI: https://doi.org/10.1007/s40618-023-02085-5

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