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Ponto K.A.,Gutenberg University Medical Center
Thyroid : official journal of the American Thyroid Association | Year: 2010

BACKGROUND: Autoimmunity against the thyrotropin receptor (TSH-R) is a key pathogenic element in Graves' disease (GD) and the autoimmune aberration may be modified by antithyroid treatment. An association between radioactive iodine (RAI) therapy for GD and the development or worsening of Graves' orbitopathy (GO) is widely quoted. RAI-associated leakage of thyroid antigen(s) leads to an increased production of TSH-R antibodies that may initiate the eye injury. SUMMARY: RAI therapy leads to prolonged worsening of autoimmunity against the TSH-R, and the number of patients entering remission of TSH-R autoimmunity is considerably lower than with other antithyroid therapies. Scientific evidence has indicated that RAI treatment for GD is associated with increased risk of occurrence or progression of GO compared with antithyroid drugs (ATD) and thyroid surgery. The risks of developing new GO or worsening of preexisting GO is around 20% after RAI and around 5% after ATD. The risk of developing severe GO after RAI is around 7%. Smoking, high levels of pretreatment serum triiodothyronine, and post-RAI hypothyroidism are associated with increased risk of GO, whereas a high TSH-R autoantibody titer is an independent risk factor for the progression of GO. In patients with mild preexisting GO, steroid prophylaxis is effective in preventing deterioration of GO. Also, routine use of prophylactic oral steroids with RAI therapy should be considered in GD patients without overt GO, but even more so in those at higher risks of eye complications such as smokers, old men, and those with severe hyperthyroidism or high TSH-R antibody titers. CONCLUSION: In contrast to ATD, remission of TSH-R autoimmunity after RAI therapy is less common, and RAI for GD is associated with definite increased risk of GO. Oral steroids are beneficial for patients with preexisting GO, particularly smokers.

Biondi B.,University of Naples Federico II | Kahaly G.J.,Gutenberg University Medical Center
Nature Reviews Endocrinology | Year: 2010

Various clinical disorders can cause hyperthyroidism, the effects of which vary according to the patient's age, severity of clinical presentation and association with other comorbidities. Hyperthyroidism is associated with increased morbidity and mortality from cardiovascular disease, although whether the risk of specific cardiovascular complications is related to the etiology of hyperthyroidism is unknown. This article will focus on patients with Graves disease, toxic adenoma and toxic multinodular goiter, and will compare the cardiovascular risks associated with these diseases. Patients with toxic multinodular goiter have a higher cardiovascular risk than do patients with Graves disease, although cardiovascular complications in both groups are differentially influenced by the patient's age and the cause of hyperthyroidism. Atrial fibrillation, atrial enlargement and congestive heart failure are important cardiac complications of hyperthyroidism and are prevalent in patients aged ≥60 years with toxic multinodular goiter, particularly in those with underlying cardiac disease. An increased risk of stroke is common in patients >65 years of age with atrial fibrillation. Graves disease is linked with autoimmune complications, such as cardiac valve involvement, pulmonary arterial hypertension and specific cardiomyopathy. Consequently, the etiology of hyperthyroidism must be established to enable correct treatment of the disease and the cardiovascular complications. © 2010 Macmillan Publishers Limited. All rights reserved.

Marcocci C.,University of Pisa | Kahaly G.J.,Gutenberg University Medical Center | Krassas G.E.,Panagia General Hospital | Bartalena L.,University of Insubria | And 7 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy. METHODS: We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 μg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score. RESULTS: At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P = 0.01) and slowed the progression of Graves' orbitopathy (P = 0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems. CONCLUSIONS: Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.) Copyright © 2011 Massachusetts Medical Society.

Muller-Forell W.,Gutenberg University Medical Center | Kahaly G.J.,Gutenberg University Medical Center
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2012

Neuroimaging of Graves' orbitopathy (GO) plays an important role in the differential diagnosis and interdisciplinary management of patients with GO. Orbital imaging is required in unclear or asymmetric proptosis, in suspected optic neuropathy and prior to decompression surgery. Especially computed tomography and magnetic resonance (MR) imaging show the actual objective morphological findings, quantitative MR imaging giving additional information concerning the acuteness or chronicity of the disease. Major morphological diagnostic criteria include a spindle like spreading of the rectus muscles without involvement of the tendon, a compression of the optic nerve in the orbital apex (crowded orbital apex syndrome) and the absence of any space occupying intraorbital process. A longer lasting course of the disease may lead to a corresponding impression of the lamina papyracae, the normally parallel configured medial wall of the orbit, similar to a spontaneous decompression. © 2011 Elsevier Ltd. All rights reserved.

Zang S.,Gutenberg University Medical Center | Kahaly G.J.,Gutenberg University Medical Center
Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry | Year: 2011

Steroids act via suppression of the immune system in two different ways: a genomic and a non-genomic pathway. While the non-genomic pathway appears to be responsible for the quick effects only a few minutes after application, the genomic pathway determines the long-time effects. Since decades, systemic steroids have been applied in the management of severe Graves' orbitopathy (GO). In GO, steroids effectively modulate both the effector cells as well as the orbital targets cells, i.e. fibroblasts and pre-adipocytes. They inhibit the release of inflammatory mediators i.e. cytokines and prostaglandins. Also, systemic steroids significantly reduce the titer of the disease relevant thyroid-stimulating immunoglobulins. A few studies only, dealing with difference in mechanisms depending on the way of administration (intravenous, oral or peribulbar) are available. Efficacy of the three ways of application is statistically different. The systemic administration of steroids has a higher efficacy than the local peribulbar application. Furthermore, evidence based and compared to the oral form, the intravenous steroid administration shows both a significantly higher response rate as well as markedly less adverse events. Thus, high dose intravenous steroid pulses are currently considered the first line-reatment for active and severe GO. © 2011 Bentham Science Publishers Ltd.

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