Search results for "graves"
showing 10 items of 128 documents
Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease
2021
Abstract Context We previously presented evidence that TSH receptor (TSHR)-stimulating autoantibodies (TSAbs) bind to and activate TSHRs but do not bind to IGF1 receptors (IGF1Rs). Nevertheless, we showed that IGF1Rs were involved in thyroid eye disease (TED) pathogenesis because TSAbs activated crosstalk between TSHR and IGF1R. Teprotumumab, originally generated to inhibit IGF1 binding to IGF1R, was recently approved for the treatment of TED (Tepezza). Objective To investigate the role of TSHR/IGF1R crosstalk in teprotumumab treatment of TED. Design We used orbital fibroblasts from patients with TED (TEDOFs) and measured stimulated hyaluronan (HA) secretion as a measure of orbital fibrobla…
A Novel Long-Term Graves’ Disease Animal Model Confirmed by Functional Thyrotropin Receptor Antibodies
2020
<b><i>Introduction:</i></b> A novel long-term murine model for Graves’ disease (GD) using repeated, long-term immunizations with recombinant adenovirus expressing the extracellular A-subunit of the human thyrotropin receptor (Ad-TSHR) was applied to evaluate the functional anti-TSHR-antibody (TSHR-Ab) profile. <b><i>Methods:</i></b> BALB/c mice received 7 immunizations with either 10<sup>10</sup> plaque-forming units of Ad-TSHR or control Ad-GFP. Naïve (nonimmuized native) mice were also studied. Three 3-weekly immunizations were followed by 4-weekly boosts until the 7th immunization. Blocking (TBAb) and stimulating (TSAb) TSHR-Ab …
Clinical Relevance of Thyroid-Stimulating Immunoglobulins in Graves' Ophthalmopathy
2011
Purpose Thyroid-stimulating immunoglobulins (TSIs) likely mediate Graves' ophthalmopathy (GO). The clinical relevance of these functional autoantibodies was assessed in GO. Design Cross-sectional trial. Participants A total of 108 untreated patients with GO. Methods Thyroid-stimulating immunoglobulins, assessed with a novel bioassay, bind to the thyrotropin receptor (TSHR) and transmit signals for cyclic adenosine monophosphate (cAMP)-dependent activation of luciferase gene expression. The cAMP/cAMP response element-binding protein/cAMP-regulatory element complex induces luciferase that is quantified after cell lysis. The TSI levels were correlated with activity and severity of GO and compa…
Is there a methimazole dose effect on remission rate in Graves' disease? Results from a long-term prospective study
1998
OBJECTIVE The optimal antithyroid drug regimen for Graves' disease remains a matter of controversy. The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long-term outcome of Graves' disease. DESIGN Extended follow-up of patients from a prospective multicentre trial, designed to study methimazole dose effects on the outcome of Graves' disease. We have reported previously that the relapse rates did not differ after a medication-free observation period of 12 months; the relapse rates were 37 and 38%, respectively. In this paper, we describe the outcome in these patients after a mean observation period of 4.3 ± 1.3 years and have looked for potential…
The necropolis of Ensisheim/Reguisheimerfeld (Haut-Rhin) : illustration of the Late Bronze Age funerary practices in Alsace
2007
In 2000, the preventive excavation of the Ensisheim/Reguisheimerfeld site (Haut-Rhin), carried out by the ANTEA SARL company, brought to light 87 funerary structures belonging to a cremation necropolis dating from the beginning of the Late Bronze Age (around 1350-1050 BC). Following study of the material, 3 successive chronological phases and a possible cultural "faciès" centred on the bend in the Rhine at Basel, Switzerland, were distinguished. The archaeo-anthropological study of the burnt bones revealed, among other things, the existence of a large number of multiple graves and of socially immature members of the society, phenomena rarely observed in the region. The analysis of the inter…
Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease
2020
PurposeThyroid eye disease (TED) is a progressive, debilitating and potentially vision-threatening autoimmune disease. Teprotumumab, a novel human monoclonal antibody, has been shown to reverse the clinical manifestations of TED. Patients receiving teprotumumab have been shown in two multicenter, randomized placebo-controlled trials to have decreased proptosis, diplopia and inflammation after 24 weeks of treatment. This study aims to analyse volumetric and inflammatory changes on orbital imaging prior to and after teprotumumab treatment from one of these trials.DesignRetrospective review.SubjectsSix patients enrolled in the phase III teprotumumab clinical trial (OPTIC, NCT03298867) with act…
La ecografía Doppler con flujo en color en el diagnóstico, tratamiento y pronóstico de la Enfermedad de Graves-Basedow
2022
Introducción La ecografía Doppler tiroidea es un método no invasivo que puede proporcionar información acerca del estado funcional de la glándula tiroidea de forma indirecta mediante el estudio de la vascularización. Cada vez más autores proponen la ecografía Doppler tiroidea como primera herramienta para el diagnóstico diferencial de la tirotoxicosis. Hipótesis La ecografía Doppler tiroidea podría ser una técnica útil para establecer el diagnóstico de la Enfermedad de Graves-Basedow (EGB), planificar la dosis de antitiroideos de síntesis y establecer la probabilidad de recidiva tras finalizar el tratamiento médico. Objetivos principales Establecer el valor de la ecografía Doppler tiroidea …
A 2013 European survey of clinical practice patterns in the management of Graves' disease
2014
SummaryObjective Management of Graves' disease (GD) in Europe was published in 1987. Aim of this survey was to provide an update on clinical practice in Europe, and to compare it with a 2011 American survey. Design Members of the European Thyroid Association (ETA) were asked to participate in a survey on management of GD, using the same questionnaire of a recent American survey. Results A total of 147 ETA members participated. In addition to serum TSH and free T4 assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (85·6%) and thyroid ultrasound (70·6%) to confirm aetiology, while isotopic studies were selected by 37·7%. Antithyroid drug (ATD) therapy was the …
Improvement of asymmetric thyroid eye disease with teprotumumab
2021
PurposeTeprotumumab, a specific blocking antibody to the insulin like growth factor 1 receptor, significantly reduced proptosis in patients with thyroid eye disease (TED) in recent clinical trials. Given its specificity, we expect it to demonstrate greater efficacy on the worse affected orbit, in patients with asymmetric TED. Herein, we investigate the differential impact of teprotumumab on the orbits of such patients.MethodsIn this pooled analysis of patients who were enrolled in the recent phase 2 (NCT01868997) and phase 3 (NCT03298867) trials, all patients with asymmetric TED (difference in exophthalmometry of ≥3 mm) were screened for eligibility. The primary outcomes of the trials, prop…
Reply to Drs. Kiaei and Molinaro Regarding the Publication “Comparison of a Bridge Immunoassay with Two Bioassays for Thyrotropin Receptor Antibody D…
2020
Dear Editor,Drs. Kiaei and Molinaro 1 put forth two criticisms of the manuscript published by us 2. They state that the experimental design of this study is flawed and that the authors falsely claim that negative Thyretain™ TSI Reporter BioAssay results for two Graves’ diseases patients undergoing drug treatments means the absence of stimulating antibodies. To substantiate this claim Drs. Kiaei and Molinaro point out that the manufacturer of the Thyretain TSI Reporter BioAssay clearly states in the package insert that “[t]he effects of various drug therapies on the performance of this Kit have not been established” 1. Second, the package insert explicitly states that “[a] negative result do…