Graves' Orbitopathy: Imperfect Treatments for a Rare Disease

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.

Wcześniejsze leczenie choroby Gravesa lekami tyreostatycznymi lub radiojodem nie wpływa na skuteczność leczenia immunosupresyjnego orbitopatii tarczycowej

“…The likely pathogenesis of this phenomenon is the sudden release of thyroid antigens by 131-I-damaged thyroid cells, causing an increase in the production of autoantibodies, including TRAb [11,13]. It is estimated that GO aggravation after 131-I treatment affects up to 20% of patients [11] and is more predominant in patients who had earlier manifested eye symptoms [2,8] or in those with prolonged hypothyroidism following radioiodine treatment [17]. Male patients are more prone to GO exacerbation [18].…”

“…The prevalence of GO tends to decline over the years, perhaps due to the decrease in smoking habits or to earlier diagnosis [4][5][6][7]. As only limited groups of GO patients are available for randomised clinical trials (RCTs), precise GO pathogenesis and targeted treatment remain uncertain [2,8]. It is believed that higher TRAb titres are present in patients with more severe GO [9,10].…”

Clinical and immunological changes in patients with active moderate-to-severe Graves̕ orbitopathy treated with very low-dose rituximab

“…Graves' orbitopathy (GO) is an autoimmune disorder of the orbital tissues that develops in 25-50% patients with Graves' disease [1,2]. It may also occur in patients without any current or prior hyperthyroidism (euthyroid or ophthalmic Graves' disease) or in hypothyroid patients due to chronic autoimmune thyroiditis [3].…”

Favorable Effect of Bromocriptine and Pentoxifylline in Mild Graves Disease Orbitopathy: A Randomized, Open, Clinical Trial

“…At present, available treatments are insufficient [4] and are focused on identifying patients with sight-threatening GO whom require aggressive intervention with glucocorticoids, orbital decompression, and/or radiotherapy. Patients with moderate to severe GO defined with lid retraction >2 mm, moderate or severe soft tissue involvement, exophthalmos >3 mm above normal, inconstant or constant diplopia, also qualify for immunosuppressive therapy [3].…”