PURPOSE: Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. DESIGN: Cross-sectional trial. PARTICIPANTS: A total of 108 untreated patients with GO. METHODS: Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compared with a TSHR binding inhibitory immunoglobulin (TBII) assay. MAIN OUTCOME MEASURES: Thyroid-stimulating immunoglobulins, activity and severity of GO, diplopia, and TBII. RESULTS: Thyroid-stimulating immunoglobulins were detected in 106 of 108 patients (98%) with GO. All 53 hyperthyroid patients were TSI positive versus 47 patients (89%) who were TBII positive. All 69 patients with active GO were TSI positive, whereas only 58 of 69 patients (84%) were TBII positive. Thyroid-stimulating immunoglobulins correlated with the activity (r=0.83, P < 0.001) and severity (r=0.81, P < 0.001) of GO. All 59 patients with GO with diplopia were TSI positive, and 50 of 59 patients (85%) were TBII positive. Among patients with moderate-to-severe and mild GO, 75 of 75 (100%) and 31 of 33 (94%) were TSI positive compared with TBII positivity in 63 of 75 (84%) and 24 of 33 (73%), respectively. The TSI levels were higher in moderate-to-severe versus mild GO (489%±137% vs. 251%±100%, P < 0.001). Chemosis and GO activity predicted TSI levels alone (P < 0.001, multivariable analysis). The TSI levels were higher in patients with chemosis (527%±131%) than in patients without chemosis (313%±127%, P < 0.001). CONCLUSIONS: Thyroid-stimulating immunoglobulins show more significant association with clinical features of GO than TBII and may be regarded as functional biomarkers for GO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
PURPOSE: Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. DESIGN: Cross-sectional trial. PARTICIPANTS: A total of 108 untreated patients with GO. METHODS: Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compared with a TSHR binding inhibitory immunoglobulin (TBII) assay. MAIN OUTCOME MEASURES: Thyroid-stimulating immunoglobulins, activity and severity of GO, diplopia, and TBII. RESULTS: Thyroid-stimulating immunoglobulins were detected in 106 of 108 patients (98%) with GO. All 53 hyperthyroidpatients were TSI positive versus 47 patients (89%) who were TBII positive. All 69 patients with active GO were TSI positive, whereas only 58 of 69 patients (84%) were TBII positive. Thyroid-stimulating immunoglobulins correlated with the activity (r=0.83, P < 0.001) and severity (r=0.81, P < 0.001) of GO. All 59 patients with GO with diplopia were TSI positive, and 50 of 59 patients (85%) were TBII positive. Among patients with moderate-to-severe and mild GO, 75 of 75 (100%) and 31 of 33 (94%) were TSI positive compared with TBII positivity in 63 of 75 (84%) and 24 of 33 (73%), respectively. The TSI levels were higher in moderate-to-severe versus mild GO (489%±137% vs. 251%±100%, P < 0.001). Chemosis and GO activity predicted TSI levels alone (P < 0.001, multivariable analysis). The TSI levels were higher in patients with chemosis (527%±131%) than in patients without chemosis (313%±127%, P < 0.001). CONCLUSIONS: Thyroid-stimulating immunoglobulins show more significant association with clinical features of GO than TBII and may be regarded as functional biomarkers for GO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Authors: N E Bufalo; R B Dos Santos; M A Marcello; R P Piai; R Secolin; J H Romaldini; L S Ward Journal: J Endocrinol Invest Date: 2014-12-28 Impact factor: 4.256
Authors: Joshua D Stein; David Childers; Shivani Gupta; Nidhi Talwar; Bin Nan; Brian J Lee; Terry J Smith; Raymond Douglas Journal: JAMA Ophthalmol Date: 2015-03 Impact factor: 7.389