Journal of Endocrinological Investigation

, Volume 38, Issue 7, pp 769–777 | Cite as

Thyroid-stimulating immunoglobulins indicate the onset of dysthyroid optic neuropathy

  • K. A. Ponto
  • T. Diana
  • H. Binder
  • N. Matheis
  • S. Pitz
  • N. Pfeiffer
  • G. J. KahalyEmail author
Original Article



Recognition of dysthyroid optic neuropathy (DON) requires sensitive diagnostic tools. Clinical assessment may fail to reliably evaluate the acuteness of DON especially if signs for inflammation are missing. Aim of this cross-sectional study was to assess the relationship between thyroid-stimulating immunoglobulins (TSI) and onset of DON.


At a multidisciplinary orbital center, serum TSI levels were measured in 180 consecutive patients with thyroid eye disease (TED) and 302 healthy controls with a FDA-cleared cell-based bioassay using a chimeric TSH receptor and a CRE-dependent luciferase.


Thirty of 180 (16.7 %) patients with TED had DON of recent onset or a past history of DON (post-DON). Optic disk swelling was present and visual-evoked potentials were pathologic in all eyes with DON of recent onset, but in one of 13 (7.7 %) with post-DON, only (p = 0.005). 19/20 (96 %) patients with DON of recent onset were TSI-positive. TSI was associated with DON of recent onset (OR: 20.96; 95 % CI 1.064–412.85, p = 0.045). All controls were TSI negative. TSI correlated with the clinical activity score (R = 0.70, p < 0.001) and higher TSI-levels were noted in active vs. inactive TED (485.1 ± 132.3 vs. 277.7 ± 143.7 %, cut-off < 140 %; p < 0.001). Six of seven (85.7 %) patients with inactive TED with recent onset DON versus one of four (25 %) with active post-DON were TSI-positive (p = 0.006). A discriminatory cut-point of 377 SRR % for TSI was determined based on a ROC analysis (sensitivity: 0.95, specificity: 0.8).


Serum TSI levels identify patients with DON of recent onset requiring urgent therapy.


Thyroid stimulating immunoglobulins Dysthyroid optic neuropathy Thyroid eye disease 



Thyroid eye disease


Thyroid stimulating immunoglobulins


Dysthyroid optic neuropathy


Thyroid stimulating hormone




European Group on Graves Orbitopathy


Clinical activity score


Thyroid binding inhibitory immunoglobulin


Percentage of specimen-to-reference ratio


Relative light units

CV %

Coefficient of variation



Katharina A Ponto is funded by the Federal Ministry of Education and Research (BMBF 01EO1003). The authors are grateful to Paul D. Olivo, MD, PhD and to Jeff Houtz for the critical evaluation of the manuscript.

Conflict of interest

Katharina A. Ponto, Tanja Diana, Harald Binder, Nina Matheis, Susanne Pitz, and Norbert Pfeiffer have nothing to disclose; George J. Kahaly consults for and has received research funding from Quidel, CA, USA. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Italian Society of Endocrinology (SIE) 2015

Authors and Affiliations

  • K. A. Ponto
    • 1
    • 4
  • T. Diana
    • 2
  • H. Binder
    • 3
  • N. Matheis
    • 2
  • S. Pitz
    • 1
  • N. Pfeiffer
    • 1
  • G. J. Kahaly
    • 2
    Email author
  1. 1.Department of OphthalmologyJohannes Gutenberg University (JGU) Medical CenterMainzGermany
  2. 2.Department of Medicine IJohannes Gutenberg University (JGU) Medical CenterMainzGermany
  3. 3.Department of Biomedical StatisticsJohannes Gutenberg University (JGU) Medical CenterMainzGermany
  4. 4.Center for Thrombosis and Hemostasis (CTH)Johannes Gutenberg University (JGU) Medical CenterMainzGermany

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