Graves' Orbitopathy: Imperfect Treatments for a Rare Disease

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laura
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Lid geworden op: 11 sep 2013, 22:42
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Graves' Orbitopathy: Imperfect Treatments for a Rare Disease

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Graves' Orbitopathy: Imperfect Treatments for a Rare Disease
Luigi Bartalena

Abstract
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.

Concluding Remarks (and Bartalena's Opinion)
GO is a rare disease, particularly in its severe expressions. It remains a therapeutic challenge and a disease with frequent unsatisfactory results, using the currently available treatments. This is partly due to the difficulty to carry out adequately powered RCTs, to the lack of complete understanding of its pathogenesis, and, therefore, to the impossibility of employing targeted therapies. This disease can be devastating in its severe forms, but it profoundly impairs the quality of life also in its milder forms due to its cosmetic and functional consequences [103]. The physician is also frustrated to admit that currently available medical treatments are not as effective as one would wish. To be provocative, I might say that GO is (in many instances) a surgical disease, and the only role of medical treatment is to abate inflammation and inactivate the disease, making it possible to send the patient to the surgeon(s) earlier. In a way, this situation is not different for Graves' hyperthyroidism: medical (pharmacological) treatment is often ineffective and associated with relapses, so that removal of the thyroid by either radioiodine or thyroidectomy is needed. In both instances, hyperthyroidism and orbitopathy, we do not intervene in the pathogenesis.

It is hoped that my frustration and pessimism be will relieved in the next few years, before my retirement.
laura

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