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Graves disease: latest understanding of pathogenesis and treatment options
Get PDFGraves disease is the most common cause of hyperthyroidism in iodine-sufficient areas. The main responsible mechanism is related to autoantibodies that bind and activate the thyrotropin receptor (TSHR). Although Graves hyperthyroidism is relatively common, no causal treatment options are available. Established treatment modalities are antithyroid drugs, which reduce thyroid hormone synthesis, radioactive iodine and surgery. However, emerging drugs that target the main autoantigen (monoclonal antibodies, small molecules, peptides) or block the immune pathway have been recently tested in clinical trials. Graves disease can involve the thyroid exclusively or it can be associated with extrathyroidal manifestations, among which Graves orbitopathy is the most common. The presence of Graves orbitopathy can change the management of the disease. An established treatment for moderate-to-severe Graves orbitopathy is intravenous glucocorticoids. However, recent advances in understanding the pathogenesis of Graves orbitopathy have allowed the development of new target-based therapies by blocking pro-inflammatory cytokine receptors, lymphocytic infiltration or the insulin-like growth factor 1 receptor (IGF1R), with several clinical trials providing promising results. This article reviews the new discoveries in the pathogenesis of Graves hyperthyroidism and Graves orbitopathy that offer several important tools in disease management
Antioxidant Therapy in Graves’ Orbitopathy
Get PDFThe balance of the cell redox state is a key point for the maintenance of cellular homeostasis. Increased reactive oxygen species (ROS) generation leads to oxidative damage of tissues, which is involved in the development of several diseases, including autoimmune diseases. Graves’ Orbitopathy (GO) is a disfiguring autoimmune-related condition associated with Graves’ Disease (GD). Patients with active, moderate-to-severe GO, are generally treated with high doses intravenous glucocorticoids (ivGCs) and/or orbital radiotherapy. On the contrary, up to recently, local ointments were the treatment most frequently offered to patients with mild GO, because the risks related to ivGCs does not justify the relatively poor benefits expected in mild GO. However, a medical treatment for these patients is heavily wanted, considering that GO can progress into more severe forms and also patients with mild GO complain with an impairment in their quality of life. Thus, based on the role of oxidative stress in the pathogenesis of GO, a therapy with antioxidant agents has been proposed and a number of studies have been performed, both in vitro and in vivo, which is reviewed here
The digitalization of physical reality: Theoretical lenses to incorporate digitalization into management research
No full textThe management literature has recently witnessed a considerable escalation of research around the implications of digitalization for firms and their environment. Yet, the conceptualization of the construct of digitalization remains elusive at best. In this chapter, we develop a taxonomy of the outcomes of the digitalization of physical reality, and of the interaction amongst digitalized units of physical reality. We maintain that these taxonomies may enhance the scope for combining extant research in integrative frameworks as well as informing management research that links digitalization and its agency in a more systematic way
Selenium in the Treatment of Graves’ Hyperthyroidism and Eye Disease
Get PDFBased on the role of oxidative stress in the pathogenesis of Graves’ hyperthyroidism (GH) and Graves’ Orbitopathy (GO), a therapy with the antioxidant agent selenium has been proposed and a number of studies have been performed, both in vitro and in vivo. In GH, reactive oxygen species (ROS) contribute to the thyroid and peripheral tissues damage. In GO, tissue hypoxia, as well as ROS, are involved in the typical changes that occur in fibroadipose orbital tissue and the perimysium of extraocular muscles. Antioxidants have been proposed to improve the effects of antithyroid drugs in GH patients, as well as the remodeling of orbital tissues in patients with GO. Here, we reviewed the literature on the possible beneficial effects and clinical use of selenium in the management of patients with GH and GO. A randomized clinical trial on the use of selenium in patients with mild GO provided evidence for a beneficial effect; no data are available on more severe forms of GO. Although the real effectiveness of selenium in patients with GH remains questionable, its use in the management of mild GO is generally believed to be beneficial, and selenium administration has been included in the clinical practice for the patients with mild eye disease
Oxidative Stress in Graves Disease and Graves Orbitopathy
No full textOxidative stress is involved in the pathogenesis of Graves hyperthyroidism (GH) and Graves orbitopathy (GO) and an antioxidant approach has been proposed for both. In GH, a disbalance of the cell redox state is associated with thyroid hyperfunction and antithyroid medications may reduce oxidative stress. Tissue hypoxia participates in the pathogenesis of GO, and oxygen free radicals are involved in the typical changes of orbital tissues as reported by in vitro and clinical studies. Antioxidant agents, especially selenium, have been proposed as a therapeutic option for GH and GO. A clinical study regarding the use of selenium in mild GO has provided evidence for a beneficial effect in the short term, even though its beneficial effects in the long term are still to be investigated. In addition to selenium, a protective role of other antioxidant agents, i.e., quercetin, enalapril, vitamin C, N-acetyl-L-cysteine and melatonin has been suggested by in vitro studies, although clinical studies are lacking. Here, we review the role of oxidative stress and antioxidant agents in GH and GO
Occurrence of Graves’ hyperthyroidism and Graves’ orbitopathy after fine-needle aspiration biopsy of thyroid nodules
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