Thyroid-stimulating immunoglobulins indicate the onset of dysthyroid optic neuropathy.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Serum TSI levels identify patients with DON of recent onset requiring urgent therapy.
Department of Ophthalmology, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. katharina.ponto@unimedizin-mainz.de.|Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. katharina.ponto@unimedizin-mainz.de.
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Ponto
Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany. tanja.diana@unimedizin-mainz.de.
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Diana
Department of Biomedical Statistics, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. binderh@uni-mainz.de.
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Binder
Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany. nina.matheis@unimedizin-mainz.de.
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Matheis
Department of Ophthalmology, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. susanne.pitz@unimedizin-mainz.de.
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Pitz
Department of Ophthalmology, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. norbert.pfeiffer@unimedizin-mainz.de.
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Pfeiffer
Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany. kahaly@ukmainz.de.
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GJ
Kahaly
D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D049970:Graves Ophthalmopathy / Q000097:blood*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood*; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D018828:Immunoglobulins, Thyroid-Stimulating
Dysthyroid optic neuropathy; Thyroid eye disease; Thyroid stimulating immunoglobulins