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      Graves' Orbitopathy: Imperfect Treatments for a Rare Disease


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          Graves' orbitopathy (GO) is the most frequent and invalidating extrathyroidal expression of Graves' disease. Its incidence and prevalence are, however, low. About three quarters of Graves' patients have no GO at diagnosis, and moderate-to-severe and severe forms represent no more that 5-6% of cases. Progression to severe forms occurs rarely, but it may be caused by risk factors, the most important being smoking and poor control of thyroid dysfunction. Lot of progress has been recently achieved in the understanding of GO pathogenesis, while the disease remains a therapeutic challenge and dilemma. Common treatments for moderate-to-severe and active forms of GO (glucocorticoids and orbital radiotherapy) frequently provide incomplete responses and may be followed by relapse or progression of GO. After the disease has been inactivated by medical treatment, many patients need rehabilitative surgery for residual manifestations (orbital decompression for exophthalmos, squint surgery for extraocular muscle dysfunction, eyelid surgery for eyelid malposition). Novel pharmacological treatments are on the horizon and might target pathogenetic mechanisms of the disease better than glucocorticoids. Clinical evidence concerning their efficacy and safety is presently lacking.

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          Most cited references 110

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          Graves' ophthalmopathy.

           S Bahn (2010)
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            Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy.

            Approximately 35% of patients with Graves' ophthalmopathy do not respond to immunosuppressive treatment. A possible explanation for this finding is that only patients with active ophthalmopathy respond to immunosuppressive treatment, whereas patients with fibrotic end stage disease do not. To distinguish between these two groups and to predict the outcome of immunosuppressive treatment, we developed a clinical activity score (CAS) based on four of the five classical signs of inflammation and tested its efficacy in a double-blind, prospective study. The CAS was determined by an opthalmologist before, on the day of, and after the start of either oral prednisone or retrobulbar irradiation in 43 patients with moderate to severe Graves' ophthalmopathy. The therapeutic outcome was determined by a second ophthalmologist unaware of the CAS stores given. Success of treatment was defined as an improvement in NOSPECS class or grade. Responders (22) and non-responders (21) did not differ in age, sex, duration or severity of their Graves' ophthalmopathy. The pretreatment CAS, however, was significantly higher in responders than in non-responders. Twelve of 22 responders and three of 21 non-responders had a CAS > or = 4 (55% vs 14%; P or = 4 had a similar duration of Graves' ophthalmopathy as patients with a CAS < 4. The clinical activity score has a high predictive value for the outcome of immunosuppressive treatment in Graves' ophthalmopathy. Disease activity, and not disease duration, is the prime determinant of therapeutic outcome.
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              Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO.


                Author and article information

                Eur Thyroid J
                Eur Thyroid J
                European Thyroid Journal
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )
                December 2013
                20 November 2013
                1 June 2014
                : 2
                : 4
                : 259-269
                Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
                Author notes
                *Prof. Luigi Bartalena, Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, Ospedale di Circolo, Viale Borri, 57, IT-21100 Varese (Italy), E-Mail

                ETA Aldo Pinchera Prize Lecture presented at the 37th Annual Meeting of the European Thyroid Association in Leiden on September 7-11, 2013.

                Copyright © 2013 by S. Karger AG, Basel
                Page count
                Figures: 2, Tables: 3, References: 103, Pages: 11
                Clinical Thyroidology / Review


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