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Ophthalmology. 2011 Nov;118(11):2279-85. doi: 10.1016/j.ophtha.2011.03.030.

Clinical relevance of thyroid-stimulating immunoglobulins in graves' ophthalmopathy.

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1
Department of Ophthalmology, University Medical Center, Mainz, Germany.

Abstract

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.

Comment in

PMID:
21684605
DOI:
10.1016/j.ophtha.2011.03.030
[Indexed for MEDLINE]

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