Alemtuzumab-induced thyroid eye disease successfully treated with a single low dose of rituximab.

Introduction: Secondary thyroid autoimmunity, especially Graves' disease (GD), frequently develops in patients with multiple sclerosis (MS) following alemtuzumab treatment (ALTZ; anti-CD52). Thyroid eye disease (TED) can also develop, and rituximab (RTX; anti-CD20) is a suitable treatment.

Case Presentation: A 37-year-old woman with MS developed steroid-resistant active moderate-to-severe TED 3 years after ALTZ, that successfully responded to a single 500 mg dose of i.

Increased Risk of Thyroid Eye Disease Following Covid-19 Vaccination.

Context: SARS-CoV-2 infection and Covid-19 vaccines have been associated with thyroid disorders.

Objective: We analyzed the risk of thyroid eye disease (TED) following Covid-19 vaccination. This was a self-controlled case series study at a tertiary referral center for TED.

Gut Microbiome Associated With Graves Disease and Graves Orbitopathy: The INDIGO Multicenter European Study.

Context: Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves disease (GD; hyperthyroidism caused by autoantibodies, TRAb, to the thyrotropin receptor, TSHR) and its progression to Graves orbitopathy (GO).

Objective: This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs).

Methods: Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

Background: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time.

Methods: Prospective observational multicentre study.

Management of Thyroid Eye Disease: A Consensus Statement by the American Thyroid Association and the European Thyroid Association.

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists.

Management of thyroid eye disease: a Consensus Statement by the American Thyroid Association and the European Thyroid Association.

Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists.

Microbiota Alterations in Patients with Autoimmune Thyroid Diseases: A Systematic Review.

Autoimmune thyroid diseases (AITDs) are chronic autoimmune disorders that cause impaired immunoregulation, leading to specific immune responses against thyroid antigens. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are the major forms of AITDs. Increasing evidence suggests a possible role of microbiota alterations in the pathogenesis and progression of AITDs.

Future Projections in Thyroid Eye Disease.

Background And Aims: This review aims to summarize current and emerging therapies for treatment of thyroid eye disease (TED), in the light of novel understanding of pathogenetic mechanisms, leading to new treatment options and clinical trials.

Methods: We reviewed and analyzed peer-reviewed literature reporting recent translational studies and clinical trials in the treatment of TED. Searches were made at www.

Therapy With Different Dose Regimens of Rituximab in Patients With Active Moderate-To-Severe Graves' Orbitopathy.

Background: Immunosuppressive therapy of Graves' orbitopathy (GO) is indicated during the active phase of disease. Intravenous steroids (IVGC) are effective in about 70% of patients, although unresponsiveness or relapse are observed. In previous studies, rituximab (RTX) has been shown to be effective in inactivating moderate-to-severe GO when used early in the disease, but its optimal dosage has never been studied in randomized clinical trials.

Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease.

Background: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity.

Efficacy Profile and Safety of Very Low-Dose Rituximab in Patients with Graves' Orbitopathy.

Rituximab (RTX), a chimeric human-murine anti-CD20 monoclonal antibody, has been used for treatment of active moderate-severe Graves' orbitopathy (GO) since 2004 as second-line therapy in patients unresponsive to intravenous steroids. We conducted an open-label prospective study (EUDRACT 2012-001980-53) in which patients were treated with a single infusion of only 100 mg RTX to analyze the efficacy and safety of this low dose. Seventeen patients, of whom nine had disease that was unresponsive to intravenous methylprednisolone and eight with newly diagnosed GO, were enrolled.

Quantification of Global Ocular Motility Impairment in Graves' Orbitopathy by Measuring Eye Muscle Ductions.

The overall changes of ocular motility in Graves' orbitopathy (GO) are not easily quantifiable with the methods currently available, especially in clinical studies. The aim of the present study was to calculate parameters that quantify the changes of ocular motility in GO in relation to the Gorman score for diplopia. We studied 100 GO patients (Group 1) and 100 controls (Group 2).

The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience.

Discrepant thyroid function tests (TFTs) are typical of inappropriate secretion of TSH (IST), a rare entity encompassing TSH-secreting adenomas (TSHoma) and Resistance to Thyroid Hormone (RTHβ) due to mutations. The differential diagnosis remains a clinical challenge in most of the cases. The objective of this study was to share our experience with patients presenting with discrepant TFTs outlining the main pitfalls in the differential diagnosis.

Asymmetry indicates more severe and active disease in Graves' orbitopathy: results from a prospective cross-sectional multicentre study.

Purpose: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy.

Methods: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres.

Prevention of Orbitopathy by Oral or Intravenous Steroid Prophylaxis in Short Duration Graves' Disease Patients Undergoing Radioiodine Ablation: A Prospective Randomized Control Trial Study.

Radioiodine (RAI) is a known risk factor for activation or occurrence of Graves' orbitopathy (GO). Several studies demonstrated that GO can be prevented by glucocorticoids (GCs) in patients with pre-existing GO. We have previously shown that Graves' disease duration (GDd) <5 years is a risk factor for RAI-induced GO.

Combined immunosuppressants and less steroids in active graves' orbitopathy?

Steroid therapy in GO is first-line treatment but has limitations, as it is potentially harmful at high doses and often refused by patients. A steroid-sparing therapy is a reasonable option as long as it is rapidly effective and devoid of long-term adverse reactions. Combined immunosuppressive therapy must be studied in randomized clinical trials designed to test efficacy and the potentially increased risk of side effects.

B cells in Graves' Orbitopathy: more than just a source of antibodies?

B cells have multiple actions on different phases of an immune reaction, mainly resulting in B and T cell-interaction (help), production of cytokines, regulation of dendritic cells and downregulation of regulatory B cells. The effectiveness of B cell depletion therapy is probably due to blockade of the antigen-presenting function of B cells, occurring very early in the setting of autoimmune reactions. B cells undergo a maturation process from stem cells during which the CD 20 antigen, which is the target of rituximab (RTX), is expressed from the stage of pre-B cells to mature and memory B cells, but not on plasma cells.

Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement.

Background: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682).

The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy.

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease, though severe forms are rare. Management of GO is often suboptimal, largely because available treatments do not target pathogenic mechanisms of the disease. Treatment should rely on a thorough assessment of the activity and severity of GO and its impact on the patient's quality of life.

Medical Treatment of Graves' Orbitopathy.

The medical treatment of Graves' orbitopathy (GO) is usually reserved to moderate to severe disease. Steroids have been widely employed and possess anti-inflammatory activity, but about 20-30% of patients are not responsive and about 20% present with disease recurrence. Immunosuppressive therapy alternative to corticosteroids may target the different antigens involved in pathogenic mechanisms of GO.

B Cell Activating Factor (BAFF) and BAFF Receptor Expression in Autoimmune and Nonautoimmune Thyroid Diseases.

Background: The B cell activating factor (BAFF) is a member of the tumor necrosis factor family, which controls the survival/proliferation of B cells and is involved in the pathogenesis of a number of autoimmune diseases. The objective of the present study was to investigate the expression of BAFF and BAFF receptor (BAFF-R) in the thyroid tissue of patients affected with autoimmune thyroid disorders (AITD) or multinodular goiter (MNG) compared with those with normal thyroids.

Methods: Immunohistochemistry was performed using a panel of antibodies against BAFF, BAFF-R, CD3, CD4, CD8, CD20, CD34, CD79a, CD1a, CD68, and CD163 on the thyroid sections of 27 patients affected with Graves' disease (GD), 23 with Hashimoto's thyroiditis (HT), 16 with nontoxic nodular goiter (NTG), and 15 with toxic nodular goiter (TG), submitted to total thyroidectomy between 2000 and 2011.

Statins may increase the risk of liver dysfunction in patients treated with steroids for active graves' orbitopathy.

Context: Intravenous glucocorticoids (IVGC) administered at high doses for the treatment of active moderate-severe Graves' orbitopathy (GO) may induce liver toxicity. Cumulative doses should not exceed 8 g and strict monitoring of liver function is recommended to avoid potentially life-threatening side effects. The 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, also known as statins, are employed to prevent major cardiovascular events.