Statins for Graves' orbitopathy (STAGO): a phase 2, open-label, adaptive, single centre, randomised clinical trial.

Background: A protective action of statins on development of Graves' orbitopathy suggests that statins might be used for treatment of the disease. We aimed to assess the efficacy of the addition of a statin, atorvastatin, to intravenous glucocorticoids (ivGCs) on Graves' orbitopathy outcomes in patients with hypercholesterolaemia.

Methods: We did a randomised, open-label, phase 2, adaptive, clinical trial at a single, tertiary, referral hospital in Pisa, Italy.

Disappearance of Anti-Thyroid Autoantibodies following Thymectomy in Patients with Myasthenia Gravis.

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.

Mechanistic Pathways of Selenium in the Treatment of Graves' Disease and Graves' Orbitopathy.

Based on the role of oxidative stress in the pathogenesis of Graves' hyperthyroidism and Graves' orbitopathy, the use of the antioxidant agent selenium has been proposed and several studies on the subject have been conducted, both in vitro and in vivo. Whereas a true benefit related to the use of selenium in patients with Graves' hyperthyroidism has been questioned, its use in patients with mild Graves' orbitopathy is generally believed to be beneficial because of which selenium has entered in the clinical practice for this eye condition.

Selenium in Graves Hyperthyroidism and Orbitopathy.

Purpose: To review the in vitro and in vivo studies supporting a role of selenium for the treatment of mild Graves orbitopathy.

Methods: Review of the current literature on the role of selenium in the management of Graves orbitopathy.

Results: Graves orbitopathy (GO) is a disfiguring and disabling disorder usually observed in patients with Graves hyperthyroidism, and more rarely in patients with hypothyroid autoimmune thyroiditis or in the absence of overt thyroid dysfunction.

Mycophenolate plus methylprednisolone versus methylprednisolone alone in active, moderate-to-severe Graves' orbitopathy (MINGO): a randomised, observer-masked, multicentre trial.

Background: European guidelines recommend intravenous methylprednisolone as first-line treatment for active and severe Graves' orbitopathy; however, it is common for patients to have no response or have relapse after discontinuation of treatment. We aimed to compare the efficacy and safety of add-on mycophenolate to methylprednisolone in comparison with methylprednisolone alone in patients with moderate-to-severe Graves' orbitopathy.

Methods: MINGO was an observer-masked, multicentre, block-randomised, centre-stratified trial done in two centres in Germany and two in Italy.

High Serum Cholesterol Is a Novel Risk Factor for Graves' Orbitopathy: Results of a Cross-Sectional Study.

Background: Limited data suggest that treatment with statins is associated with a reduced risk of Graves' orbitopathy (GO) in patients with Graves' disease (GD), attributed to the anti-inflammatory rather than to the hypolipemic effects of these medications. The aim of the present study was to investigate whether there is an association between high cholesterol and GO. The primary outcome was the relation between GO and low-density lipoprotein (LDL)-cholesterol.

Does Graves' Orbitopathy Ever Disappear? Answers to an Old Question.

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.

Antioxidant Actions of Selenium in Orbital Fibroblasts: A Basis for the Effects of Selenium in Graves' Orbitopathy.

Background: A recent clinical trial has shown a beneficial effect of the antioxidant agent selenium in Graves' orbitopathy (GO). In order to shed light on the cellular mechanisms on which selenium may act, this study investigated its effects in cultured orbital fibroblasts.

Methods: Primary cultures of orbital fibroblasts from six GO patients and six control subjects were established.

VARIABLES AFFECTING THE LONG-TERM OUTCOME OF GRAVES ORBITOPATHY FOLLOWING HIGH-DOSE INTRAVENOUS GLUCOCORTICOID PULSE THERAPY IN PATIENTS NOT TREATED WITH ORBITAL RADIOTHERAPY.

Objective: Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC.

Methods: We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months.

Natural history of graves' orbitopathy after treatment.

Intravenous glucocorticoids are used for Graves' orbitopathy, alone or associated with/followed by additional treatments (orbital radiotherapy, orbital decompression, palpebral or eye surgery). However, the relation between associated/additional treatments and other variables with Graves' orbitopathy outcome following intravenous glucocorticoids is not clear. Thus, the present study was conducted to investigate retrospectively the impact of associated/additional treatments and other variables on Graves' orbitopathy outcome after intravenous glucocorticoids.

Dissecting the Genetic Susceptibility to Graves' Disease in a Cohort of Patients of Italian Origin.

Graves' disease (GD) is an autoimmune oligogenic disorder with a strong hereditary component. Several GD susceptibility genes have been identified and confirmed during the last two decades. However, there are very few studies that evaluated susceptibility genes for GD in specific geographic subsets.

Age and Dose Are Major Risk Factors for Liver Damage Associated with Intravenous Glucocorticoid Pulse Therapy for Graves' Orbitopathy.

Background: High-dose intravenous glucocorticoid (ivGC) pulse therapy, which is commonly used for Graves' orbitopathy (GO), has been associated with acute liver damage (ALD), resulting in a fatal outcome in a few cases. No certain risk factors for ALD have been established. Consequently, a large retrospective cohort study was performed.

PREGO (presentation of Graves' orbitopathy) study: changes in referral patterns to European Group On Graves' Orbitopathy (EUGOGO) centres over the period from 2000 to 2012.

Background/aims: The epidemiology of Graves' orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time.

Methods: Prospective observational study of European Group On Graves' Orbitopathy (EUGOGO) centres.

Intravenous glucocorticoid therapy for Graves' ophthalmopathy and acute liver damage: an epidemiological study.

Objective: Intravenous glucocorticoid (i.v.GC) pulse therapy for Graves' ophthalmopathy (GO) can be associated with acute liver damage (ALD), which was roughly estimated to occur in ∼1% of patients, with an overall mortality of 0.

Role of the underlying thyroid disease on the phenotype of Graves' orbitopathy in a tertiary referral center.

Background: Clinically overt Graves' orbitopathy (GO) is associated with Graves' disease (GD) in approximately 95% of cases, whereas the remaining 5% is observed in patients with hypothyroid autoimmune thyroiditis (AT) or without overt thyroid dysfunction (euthyroid GO). However, it is not known whether there is a difference in terms of GO phenotype between patients with GD and those with hypothyroid AT or without thyroid dysfunction, and hence this is investigated here.

Methods: The study design was to evaluate retrospectively all consecutive patients with a recent manifestation of GO, seen at their first visit to a tertiary referral center over a period of 10 years.

Spontaneous improvement of untreated mild Graves' ophthalmopathy: Rundle's curve revisited.

Background: According to Rundle's curve, Graves' ophthalmopathy (GO) worsens during an initial phase up to a peak of maximum severity, then improves and reaches a static plateau, with the activity curve preceding the severity curve by a few months. To our knowledge, no studies have tried to replicate Rundle's curve, and very few have investigated the natural history of GO. Here, we studied GO natural history retrospectively and tried to identify factors that may affect it.

Thyroid volume and severity of Graves' orbitopathy.

Background: Graves' orbitopathy (GO) is thought to be related to one or more autoantigens present in the thyroid and in orbital tissues. Although this may not imply a quantitative relation between thyroid antigens and degree of GO, which in turn is a risk factor for a more pronounced GO, we postulated that the severity of GO may parallel the amount of thyroid tissue, namely, the size of the thyroid gland. This hypothesis is also based on the observation that patients with Graves' disease presenting with large goiters tend to have more severe hyperthyroidism.

Enalapril reduces proliferation and hyaluronic acid release in orbital fibroblasts.

Background: Orbital fibroblast proliferation and hyaluronic acid (HA) release are responsible for some of the clinical features of Graves' ophthalmopathy (GO). Thus, inhibition of these processes may be a possible therapeutic approach to this syndrome. Enalapril, a widely used antihypertensive drug, was found to have some inhibitory actions on fibroblast proliferation in cheloid scars in vivo, based on which we investigated its effects in primary cultures of orbital fibroblasts from GO patients and control subjects.

Oxidative stress in graves' disease.

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.

Treatment options for Graves' orbitopathy.

Introduction: Treatment of Graves' orbitopathy (GO) is a difficult challenge and should be performed through a multidisciplinary approach.

Areas Covered: This review covers the current treatment of hyperthyroidism and its effect on the course of GO. Treatment options for GO, according to its severity and activity, are discussed.

Outcome of Graves' orbitopathy after total thyroid ablation and glucocorticoid treatment: follow-up of a randomized clinical trial.

Context: In a previous study, we found that total thyroid ablation (thyroidectomy plus (131)I) is associated with a better outcome of Graves' orbitopathy (GO) compared with thyroidectomy alone, as observed shortly (9 months) after glucocorticoid (GC) treatment.

Objective: The objective of the study was to evaluate the outcome of GO in the same patients of the previous study over a longer period of time.

Design: This was a follow-up of a randomized study.