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Claudio Marcocci Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy

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Marenza Leo Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy

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Maria Antonietta Altea Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy

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Increased reactive oxygen species (ROS) generation and the consequent oxidative damage are involved in the development of several diseases, including autoimmune diseases. Graves’ disease is an autoimmune disorder characterized by hyperthyroidism and, less frequently, orbitopathy. Hyperthyroidism is characterized by increased oxidative stress. Untreated hyperthyroidism is associated with an increase of several parameters of oxidative stress and in most studies (but not all) by an increase of antioxidant defense enzymes. Restoration of euthyroidism with antithyroid drug is associated with a reversal of the biochemical abnormalities associated with oxidative stress. Animal and human studies suggest that increased ROS may directly contribute to some clinical manifestation of the disease, including orbitopathy. Antioxidants administered alone improve some clinical signs and symptoms of hyperthyroidism and, when associated with antithyroid drugs, induce a more rapid control of clinical manifestations and a faster achievement of euthyroidism. A large randomized clinical trial has shown that antioxidant supplementation (selenium) may also be beneficial for mild Graves’ orbitopathy.

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Elena Sabini Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Marenza Leo Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Barbara Mazzi Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Roberto Rocchi Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Francesco Latrofa Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Marco Nardi Ophthalmopathy Unit I, Department of Surgical, Medical and Molecular Pathology, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Paolo Vitti Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Claudio Marcocci Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Michele Marinò Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Objectives: There is a general belief that Graves’ orbitopathy (GO) is a “chronic” disease, namely that patients’ eyes do not return to how they were before GO appeared. Here, we investigate this issue from both the patient’s and the physician’s point of view. Study Design: We studied the disappearance of GO, regardless of treatment, in all consecutive patients with a GO history of at least 10 years who came for a follow-up visit over a period of 5 years. Patients underwent an ophthalmological examination and were asked to answer a questionnaire on self-perception related to GO. Results: We studied 99 consecutive patients with a GO duration ≥10 years. Between the first and the last observation, patients received several types of treatment for their thyroid disease and/or for GO. At the end of follow-up, GO was considered disappeared based on objective criteria in 8 patients (∼8%) and based on subjective criteria in 24 patients (∼24%). When we considered both subjective and objective criteria, only 2 patients (∼2%) had all criteria fulfilled and could be considered as GO-free. Conclusions: GO is a chronic disease in the vast majority of patients. Even after a very long time since its onset, complete disappearance is rare, although a minority of patients believe they do not have GO anymore and an even lower proportion do not have relevant GO signs. Our findings have obvious implications in patient management and counseling.

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Giovanna Rotondo Dottore Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Marenza Leo Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Roberta Ricciardi Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa and University Hospital of Pisa, Pisa, Italy
Department of Surgical, Medical and Molecular Pathology, Division of Thoracic Surgery, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Michelangelo Maestri Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Ilaria Bucci Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Marco Lucchi Department of Surgical, Medical and Molecular Pathology, Division of Thoracic Surgery, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Franca Melfi Department of Surgical, Medical and Molecular Pathology, Division of Thoracic Surgery, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Melania Guida Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Anna De Rosa Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Loredana Petrucci Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Ilaria Ionni Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Giulia Lanzolla Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Francesca Nicolì Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Michele Mantuano Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Debora Ricci Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Francesco Latrofa Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Stefano Mariotti Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy

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Claudio Marcocci Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Michele Marinò Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy

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Objectives: The thymus plays a central role in immune tolerance, which prevents autoimmunity. Myasthenia gravis (MG) is commonly associated with thymoma or thymus hyperplasia, and it can coexist with autoimmune thyroid diseases. However, the role of the thymus in thyroid autoimmunity remains to be clarified, which we investigated here. Study Design: The study design entailed the inclusion of consecutive MG patients and the measurement of anti-thyroid autoantibodies at baseline and, limited to autoantibody-positive patients, also at 24 and 48 weeks. One hundred and seven MG patients were studied. The main outcome measure was the behaviour of anti-thyroglobulin autoantibodies (TgAbs) and anti-thyroperoxidase autoantibodies (TPOAbs) over time in relation to thymectomy. Results: Serum TgAbs and/or TPOAbs were detected in ∼20% of patients in the absence of thyroid dysfunction. The prevalence of positive serum TgAbs and/or TPOAbs decreased significantly (p = 0.002) over the follow-up period in patients who underwent thymectomy, but not in patients who were not thymectomized. When the analysis was restricted to TgAbs or TPOAbs, findings were similar. On the same line, there was a general trend towards a reduction in the serum concentrations of anti-thyroid autoantibodies in patients who underwent thymectomy, which was significant for TPOAbs (p = 0.009). Conclusions: Our findings suggest a role of the thymus in the maintenance of humoral thyroid autoimmunity.

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