K A Ponto1,2, T Diana3, H Binder4, N Matheis5, S Pitz6, N Pfeiffer7, G J Kahaly8. 1. Department of Ophthalmology, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. katharina.ponto@unimedizin-mainz.de. 2. Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. katharina.ponto@unimedizin-mainz.de. 3. Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany. tanja.diana@unimedizin-mainz.de. 4. Department of Biomedical Statistics, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. binderh@uni-mainz.de. 5. Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany. nina.matheis@unimedizin-mainz.de. 6. Department of Ophthalmology, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. susanne.pitz@unimedizin-mainz.de. 7. Department of Ophthalmology, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany. norbert.pfeiffer@unimedizin-mainz.de. 8. Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany. kahaly@ukmainz.de.
Abstract
PURPOSE: 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.
PURPOSE: 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.
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