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      Outcome of thyroid associated ophthalmopathy treated by radiation therapy

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          Abstract

          Thyroid associated orbitopathy is a common manifestation of Graves disease. Many options can be considered for treatment. In this case series, we reviewed the medical records of 17 patients who received radiation therapy (RT) for GO in a tertiary care center between 1997 and 2007. All patients received 20 Gy to both orbits and 12 of them (71%) had already received one or more trials of steroid therapy prior to RT. After a median follow-up of 2 years, a subjective improvement in exophthalmos and vision was reported by all patients at the end of RT but only 3 patients reported a decrease in their diplopia immediately after therapy. Symptoms continued to improve with time in many patients: 22% had complete reversal of their symptoms and signs, and the remaining 78% had partial improvement. Two patients developed recurrent signs and symptoms, both of them were smokers who continued to smoke after treatment. About 60-65% of patients responded favorably to RT alone which increased to 87-97% when RT is combined with steroids. No patients developed late toxicity during the follow-up period. We conclude that RT is an effective treatment option in GO even in patients who failed previous treatment with steroids or surgical decompression. Based on our own clinical experiences and the literature data, the combination of RT and intravenous corticosteroid administration may improve the response rate.

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          Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy.

          The chief clinical characteristics of Graves' disease are hyperthyroidism and ophthalmopathy. The relation between the two and the effect of treatment for hyperthyroidism on ophthalmopathy are unclear. We studied 443 patients with Graves' hyperthyroidism and slight or no ophthalmopathy who were randomly assigned to receive radioiodine, radioiodine followed by a 3-month course of prednisone, or methimazole for 18 months. The patients were evaluated for changes in the function and appearance of the thyroid and progression of ophthalmopathy at intervals of 1 to 2 months for 12 months. Hypothyroidism and persistent nyperthyroiaism were promptly corrected. Among the 150 patients treated with radioiodine, ophthalmopathy developed or worsened in 23 (15 percent) two to six months after treatment. The change was transient in 15 patients, but it persisted in 8 (5 percent), who subsequently required treatment for their eye disease. None of the 55 other patients in this group who had ophthalmopathy at base line had improvement in their eye disease. Among the 145 patients treated with radioiodine and prednisone, 50 (67 percent) of the 75 with ophthalmopathy at base line had improvement, and no patient had progression. The effects of radioiodine on thyroid function were similar in these two groups. Among the 148 patients treated with methimazole, 3 (2 percent) who had ophthalmopathy at base line improved, 4 (3 percent) had worsening of eye disease, and the remaining 141 had no change. Radioiodine therapy for Graves' hyperthyroidism is followed by the appearance or worsening of ophthalmopathy more often than is therapy with methimazole. Worsening of ophthalmopathy after radioiodine therapy is often transient and can be prevented by the administration of prednisone.
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            Graves' ophthalmopathy: current concepts regarding pathogenesis and management.

            Referring to the hyperadrenergic theory on the pathogenesis of Graves' ophthalmopathy, a 1934 JAMA editorial (513) stated "the mechanism of exophthalmos is well understood though the knowledge would seem to be poorly disseminated." Several subsequent theories on pathogenesis, stated equally emphatically, have experienced a similar fate to that prompting this remark, but not before negatively impacting upon the management of patients suffering from this disorder. Thus, it is with an element of caution that we conclude that the sequence of events contributing to the pathogenesis of Graves' ophthalmopathy has become progressively more lucid, due to the assiduous efforts of many investigators in this field. Demonstration of an inextricable link between the eye and the thyroid in Graves' ophthalmopathy seems limited only by our ability to detect subtle involvement of one or the other of these two organs in exceptional cases, although not all authors share this viewpoint (514). The factors modulating the degree of expression of the thyroid component, such as concurrent lymphocytic thyroiditis or qualitative differences in TRAb seem more tangible than those affecting the clinical expression of eye involvement. Environmental factors such as smoking are associated, to a degree that matches or surpasses that known for genetic predisposition to this disorder. Local anatomy, including such factors as vulnerability to obstruction of venous drainage, must play a role as evidenced by asymmetric eye involvement and rapid relief of inflammatory changes after orbital decompression surgery. The transition from palliative to curative measures in Graves' ophthalmopathy will require further advances in our understanding of the putative shared thyroid-eye antigens, demonstration that these antigens are etiologically important and concomitant advances in antigen-specific immune therapy.
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              Smoking and thyroid disorders--a meta-analysis.

              Smoking has been associated with Graves' disease, but it remains unclear if the association is present in other thyroid disorders. Graves' disease, Graves' ophthalmopathy, toxic nodular goitre, non-toxic goitre, post-partum thyroid disease, Hashimoto's thyroiditis, or hypothyroidism. A search of MEDLINE identified 25 studies on the association between smoking and thyroid diseases. In Graves' disease eight studies were available showing an odds ratio (OR) of 3.30 (95% confidence interval (CI): 2.09-5.22) in current smokers compared with never smokers. In ex-smokers there was no significant excess risk of Graves' disease (OR=1.41, 95% CI: 0.77-2.58). The OR associated with ever smoking in Graves' ophthalmopathy (4.40, 95% CI: 2.88-6.73, six studies) was significantly higher than in Graves' disease (1.90, 95% CI: 1.42-2.55, two-sided P-value <0.01). Ever smoking was not associated with toxic nodular goitre (OR=1.27, 95% CI: 0.69-2.33, three studies), while there was an increased risk of non-toxic goitre in smokers if men were excluded (OR=1.29, 95% CI: 1.01-1.65, eight studies). The risk associated with smoking was significantly lower in men than in women for both Graves' disease and non-toxic goitre. Hashimoto's thyroiditis and post-partum thyroid dysfunction were also associated with smoking while the association with hypothyroidism did not reach statistical significance. Cessation of smoking seems associated with a lower risk of Graves' disease than current smoking. Smoking increases the risk of Graves' ophthalmopathy beyond the risk associated with Graves' disease alone. Smoking cessation may lead to a decrease in morbidity from Graves' disease, especially in women.
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                Author and article information

                Journal
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central
                1748-717X
                2011
                13 May 2011
                : 6
                : 46
                Affiliations
                [1 ]Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
                [2 ]Division of Endocrinology and Metabolism, American University of Beirut Medical Center, Beirut, Lebanon
                Article
                1748-717X-6-46
                10.1186/1748-717X-6-46
                3108307
                21569461
                04d6dd35-28e1-4566-9cc3-94c8e49389fe
                Copyright ©2011 Abboud et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 September 2010
                : 13 May 2011
                Categories
                Short Report

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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