Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO.

Department of Clinical Medicine, University of Insubria, 21100 Varese, Italy.
European Journal of Endocrinology (Impact Factor: 3.14). 04/2008; 158(3):273-85. DOI:10.1530/EJE-07-0666
Source: PubMed
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    ABSTRACT: Orbital fibroblast differentiation to adipocytes is a peroxisome proliferator-activated receptor g (PPARg)-dependent process essential for pathogenic tissue remodeling in Graves' orbitopathy (GO). PPARg2 Pro(12)Ala polymorphism modulates expression and/or function of the molecule encoded by this gene and is a promising locus of GO. Here, we analyzed associations of PPARg2 Pro(12)Ala with clinical manifestation of GO in 742 Polish Caucasians including 276 Graves' disease (GD) patients. In our study, the Ala(12) allele and Ala(12) variant (Ala(12)Ala and/or Pro(12)Ala genotype) decreased the risk of GO (p = 0.000012 and p = 0.00013). Moreover, Ala(12)Ala genotype was observed only in patients without GO (p = 0.002). GD patients with Ala(12) variant had less active and less severe eye symptoms. Female carriers of the Ala(12) allele rarely developed GO, but the marker was not related to symptoms of GO. The opposite finding was recorded in males, in whom the studied polymorphism was related to activity, but not to the development, of GO. In Ala(12) variant carriers without familial history of thyroid disease, risk of GO was lower than in persons with a familial background. The Ala(12) allele seemed to protect smokers from GO, but in nonsmokers, such a relation was not obvious. A multivariate analysis indicated the Pro(12)Ala marker as an independent risk factor of eye symptoms (p = 0.0001) and lack of Ala increases the risk of GO 3.24-fold. In conclusion, the gain-of-function Ala(12) variant protects against GO and modulates the course of the disease.
    Immunogenetics 04/2013; · 2.89 Impact Factor
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    ABSTRACT: Graves' ophthalmopathy (GO) is one of the frequent manifestations of the disorder which is an inflammatory process due to fibroblast infiltration, fibroblast proliferation and accumulation of glycosaminoglycans. Eye irritation, dryness, excessive tearing, visual blurring, diplopia, pain, visual loss, retroorbital discomfort are the symptoms and they can mimic carotid cavernous fistulas. Carotid cavernous fistulas are abnormal communications between the carotid arterial system and the cavernous sinus. The clinical manifestations of GO can mimic the signs of carotid cavernous fistulas. Carotid cavernous fistulas should be considered in the differential diagnosis of the GO patients especially who are not responding to the standard treatment and when there is a unilateral or asymmetric eye involvement. Here we report the second case report with concurrent occurrence of GO and carotid cavernous fistula in the literature.
    Indian Journal of Ophthalmology 04/2013; · 1.02 Impact Factor
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    ABSTRACT: Glucocorticoids are the mainstay of immunosuppression for active moderate-severe Graves' orbitopathy (GO). Aim: to analyze the response to therapy and the contribution of glucocorticoid receptor (GR) gene polymorphisms to the therapeutic outcome of intravenous glucocorticoids (IVGC) in active moderate-severe GO. Methods: we have studied 58 patients treated with 7.5 g i.v. methylprednisolone (cumulative dose). Ophthalmological assessment was performed at baseline and at 6-8, 12-16 and 24-30 weeks after the first infusion. Three GR gene polymorphisms, ER22/23EK, N363S and Bcl1, which have been associated to variable sensitivity to steroids, were studied in 43/58 patients. The therapeutic outcomes defined as: 1) reduction of the clinical activity score (CAS) ≥2 points or 2) reduction of proptosis ≥2 mm or 3) improvement of diplopia according to the Gorman score, were also studied in relation to treatment schedule, age, gender, duration of thyroid or GO, smoking habits, serum TSH-receptor autoantibodies (TRAb) levels. Results: 70% of patients responded and had GO inactivation (CAS< 4) as early as 6-8 weeks. At 12-16 weeks the proportion of patients who became inactive increased of another 10% up to a total of 80%. ER22/23EK, N363S polymorphisms were present only in about 7%, while the Bcl1 variant in 30% of patients; no significant association of any of the GR polymorphisms with either the therapeutic response or the occurrence of side effects was observed. Conclusions: most patients with active GO respond to IVGC as early as 6-8 weeks of therapy and the analyzed GR polymorphisms do not influence the therapeutic effect of steroids. Questions arise about the need of continuing therapy up to 12 weeks in non responders. We suggest that these patients may be switched to other treatments alone or in combination with steroids.
    European Journal of Endocrinology 10/2013; · 3.14 Impact Factor

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