Urticarial vasculitis in a young woman with Graves hyperthyroidism.
Ontology highlight
ABSTRACT:
SUBMITTER: Hung YT
PROVIDER: S-EPMC9067381 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Tremelimumab and ipilimumab are monoclonal antibodies directed against the extracellular domain of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and have been used as immunotherapies against immune checkpoints that suppress T-cell activation. Anti-CTLA-4 antibody-based therapies have been shown to be effective in treating various cancers including metastatic melanoma. However, a few immune-related adverse events including hypophysitis and thyroid disorder have been reported, mostly developed within the first year of receiving treatment. We report a case of tremelimumab-induced Graves hyperthyroidism in a 55-year-old man who was diagnosed with metastatic melanoma after 8 years of tremelimumab therapy. He had no personal or family history of thyroid or autoimmune diseases. His biochemical profile was in keeping with Graves disease, with raised serum free thyroid hormones, suppressed thyroid-stimulating hormone concentration, and raised thyrotropin receptor antibody level. He was treated with carbimazole as part of the block and replace therapy, without complications. Tremelimumab therapy was temporarily discontinued and recommenced when he was rendered biochemically euthyroid. There has been no further relapse of Graves hyperthyroidism since the discontinuation of block and replace therapy. The mechanistic profile of anti-CTLA-4-induced thyroid dysfunction and the long-term endocrine safety of this therapeutic approach remain unclear. It is important to monitor thyroid functions in patients receiving anti-CTLA-4 therapies, as their effects on endocrine systems could be more latent or prolonged than the data from current clinical trials suggest. Antithyroid drug therapy was safe and effective alongside anti-CTLA-4 therapy without compromising antitumour treatment efficacy.
| S-EPMC5527187 | biostudies-literature
Project description:BackgroundHypocomplementemic urticarial vasculitis (HUV) is a rare systemic vasculitis. We aimed to describe the kidney involvement of HUV in a multicenter national cohort with an extended follow-up.MethodsAll patients with HUV (international Schwartz criteria) with a biopsy-proven kidney involvement, identified through a survey of the French Vasculitis Study Group (FVSG), were included. A systematic literature review on kidney involvement of HUV was performed.ResultsTwelve patients were included, among whom 8 had positive anti-C1q antibodies. All presented with proteinuria, from mild to nephrotic, and 8 displayed acute kidney injury (AKI), requiring temporary haemodialysis in 2. Kidney biopsy showed membrano-proliferative glomerulonephritis (MPGN) in 8 patients, pauci-immune crescentic GN or necrotizing vasculitis in 3 patients (with a mild to severe interstitial inflammation), and an isolated interstitial nephritis in 1 patient. C1q deposits were observed in the glomeruli (n = 6), tubules (n = 4) or renal arterioles (n = 3) of 8 patients. All patients received corticosteroids, and 9 were also treated with immunosuppressants or apheresis. After a mean follow-up of 8.9 years, 6 patients had a preserved renal function, but 2 patients had developed stage 3-4 chronic kidney disease (CKD) and 4 patients had reached end-stage kidney disease (ESKD), among whom 1 had received a kidney transplant.ConclusionRenal involvement of HUV can be responsible for severe AKI, CKD and ESRD. It is not always associated with circulating anti-C1q antibodies. Kidney biopsy shows mostly MPGN or crescentic GN, with frequent C1q deposits in the glomeruli, tubules or arterioles.
| S-EPMC8851735 | biostudies-literature
Project description:Graves' hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves' hyperthyroidism. The current therapies under investigation include biologics, small molecules, and peptide immunomodulation. There is a growing focus on TSHR-specific treatment modalities, which carry the advantage of eliciting a specific, targeted approach, with the aim of avoiding disruption of the functioning immune system. These therapies present a new opportunity to supersede the inadequate treatments currently available for some Graves' patients, offering hope of successful restoration of euthyroidism without the need for ongoing therapy. Several of these therapeutic options have the potential to translate into clinical practice in the near future. This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves' hyperthyroidism.
| S-EPMC7567404 | biostudies-literature
Project description:BackgroundGraves' is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of thyroid stimulating hormone (TSH) and stimulates the thyroid hormone receptor (TSHR), which results in hyperthyroidism (overactive thyroid gland) and goiter. Methimazole (MMI) is used for hyperthyroidism treatment for patients with Graves' disease.MethodsWe have developed a model using a system of ordinary differential equations for hyperthyroidism treatment with MMI. The model has four state variables, namely concentration of MMI (in mg/L), concentration of free thyroxine - FT4 (in pg/mL), and concentration of TRAb (in U/mL) and the functional size of the thyroid gland (in mL) with thirteen parameters. With a treatment parameter, we simulate the time-course of patients' progression from hyperthyroidism to euthyroidism (normal condition). We validated the model predictions with data from four patients.ResultsWhen there is no MMI treatment, there is a unique asymptotically stable hyperthyroid state. After the initiation of MMI treatment, the hyperthyroid state moves towards subclinical hyperthyroidism and then euthyroidism.ConclusionWe can use the model to describe or test and predict patient treatment schedules. More specifically, we can fit the model to individual patients' data including loading and maintenance doses and describe the mechanism, hyperthyroidism→euthyroidism. The model can be used to predict when to discontinue the treatment based on FT4 levels within the physiological range, which in turn help maintain the remittance of euthyroidism and avoid relapses of hyperthyroidism. Basically, the model can guide with decision-making on oral intake of MMI based on FT4 levels.
| S-EPMC5759289 | biostudies-literature
Project description:Objective: Graves' disease is the commonest cause of hyperthyroidism in populations with sufficient dietary iodine intake. Anti-thyroid drugs (ATD) are often used as the initial treatment for Graves' hyperthyroidism, however there is a paucity of data relating the dose of ATD therapy to the effect on thyroid hormone levels, increasing the risk of both over- and under-treatment. We aimed to determine the pharmacodynamic response to the ATD carbimazole. Design: Retrospective cohort study. Methods: Participants were patients (n = 441) diagnosed with Graves' disease at Imperial College Healthcare NHS Trust between 2009 and 2018. The main outcome measure was change in thyroid hormone levels in response to ATD. Results: Baseline thyroid hormone levels were positively associated with TSH receptor antibody titres (P < 0.0001). Baseline free triiodothyronine (fT3) were linearly related to free thyroxine (fT4) levels in the hyperthyroid state (fT3 = fT4*0.97-11), and fell proportionately with carbimazole. The percentage falls in fT4 and fT3 per day were associated with carbimazole dose (P < 0.0001). The magnitude of fall in thyroid hormones after the same dose of carbimazole was lower during follow up than at the initiation visit. The fall in thyroid hormone levels approximated to a linear response if assessed at least 3 weeks after commencement of carbimazole. Following withdrawal of antithyroid drug treatment, the risk of relapse was greater in patients with higher initial fT4, initial TSH receptor antibody titre, males, smokers, and British Caucasian ethnicity. Conclusion: We identify a dose-response relationship for fall in thyroid hormones in response to carbimazole to aid in the selection of dose for Graves' hyperthyroidism.
| S-EPMC7236601 | biostudies-literature
Project description:BackgroundBoth Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) are associated with significant adverse health consequences. All conventional treatment options have limitations regarding efficacy and safety. Most importantly, they do not specifically address the underlying immunological mechanisms. We aim to review the latest development of treatment approaches in these two closely related disorders.SummaryImmunotherapies of GH have recently demonstrated clinical efficacy in preliminary studies. They include ATX-GD-59, an antigen-specific immunotherapy which restores immune tolerance to the thyrotropin receptor; iscalimab, an anti-CD40 monoclonal antibody which blocks the CD40-CD154 costimulatory pathway in B-T cell interaction; and K1-70, a thyrotropin receptor-blocking monoclonal antibody. Novel treatment strategies have also become available in GO. Mycophenolate significantly increased the overall response rate combined with standard glucocorticoid (GC) treatment compared to GC monotherapy. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, displayed strong anti-inflammatory action in GC-resistant cases. Teprotumumab, an anti-insulin-like growth factor 1 receptor monoclonal antibody, resulted in remarkable improvement in terms of disease activity, proptosis, and diplopia. Further, rituximab appears to be useful in active disease of recent onset without impending dysthyroid optic neuropathy.Key messagesTherapeutic advances will continue to optimize our management of GH and associated orbitopathy in an effective and safe manner.
| S-EPMC7802437 | biostudies-literature
Project description:BackgroundGraves' disease is the most common form of autoimmune thyroid disorder, characterized by hyperthyroidism due to circulating autoantibodies. To address the pathological features and establish a therapeutic approach of this disease, an animal model carrying the phenotype of Graves' disease (GD) in concert with Graves' Ophthalmopathy (GO) will be very important. However, there are no ideal animal models that are currently available. The aim of the present study is to establish an animal model of GD and GO disease, and its pathological features were further characterized.MethodsA recombinant plasmid pcDNA3.1- T289 was constructed by inserting the TSHR A-subunit gene into the expression vector pcDNA3.1, and genetic immunization was successfully performed by intramuscular injection of the plasmid pcDNA3.1-T289 on female 8-week-old BALB/c mice. Each injection was immediately followed by in vivo electroporation using ECM830 square wave electroporator. Morphological changes of the eyes were examined using 7.0T MRI scanner. Levels of serum T4 and TSHR antibodies (TRAb) were assessed by ELISA. The pathological changes of the thyroid and orbital tissues were examined by histological staining such as H&E staining and Alcian blue staining.ResultsMore than 90% of the immunized mice spontaneously developed goiter, and about 80% of the immunized mice manifested increased serum T4 and TRAb levels, combined with hypertrophy and hyperplasia of thyroid follicles. A significantly increased synthesis of hyaluronic acid was detected in in the immunized mice compared with the control groups.ConclusionWe have successfully established an animal model manifesting Graves' hyperthyroidism and ophthalmopathy, which provides a useful tool for future study of the pathological features and the development of novel therapies of the diseases.
| S-EPMC5358867 | biostudies-literature
Project description:ObjectiveSelenium (Se) supplementation has been suggested in the treatment of Graves' disease (GD). We sought to investigate Se prescription patterns for GD across European countries.MethodsMembers of the European Thyroid Association were invited to participate in an online survey investigating the use of Se in GD either without or with orbitopathy (GO). Of 872 invited members, 244 (28%) completed the survey. After exclusion of basic scientists and non-European members, 197 responses were retrieved out of clinical trials (nearly half of clinician members), of whom 61 do not use Se. Thus, 136 respondents remained for further analyses.ResultsAmong the 136 analyzed respondents, most (64.7%) were not aware of the Se status in their populations, did not assess Se levels (78.7%), nor considered iodine status (74.3%). In GD without GO, 38.2% recommend Se supplementation ("sometimes" [27.2%], "frequently" [5.9%] or "always" [5.1%]). When GO occurs, 94.1% recommend Se supplementation ("sometimes" [39%], "frequently" [30.1%] or "always" [25%]). Of these, 60.1% recommend Se as an alternative to watchful waiting in patients with mild ocular involvement and 44.9% as an adjuvant to the established treatment modalities in patients with moderate to severe ocular involvement.ConclusionsIn Graves' hyperthyroidism without GO, 38.2% of ETA (European Thyroid Association) members recommend Se supplementation. Conversely, Se is recommended by the majority of respondents in GO, both in patients with mild and moderate to severe ocular involvement. This clinical practice is partially in disagreement with current European treatment guidelines that recommend Se as a 6-month treatment in mild GO only.
| S-EPMC6381891 | biostudies-literature
Project description:Newly identified nuocytes play an important role in Th2 cell mediated immunity such as protective immune responses to helminth parasites, allergic asthma and chronic rhinosinusitis. However, the contributions of nuocytes in the occurrence and development of Graves' hyperthyroidism remains unknown. Previous studies found that there was a predominant Th2 phenotype in patients with Graves' hyperthyroidism, it might relate to polarization of nuocytes. Nuocytes were defined by transcription factor RORα, various cell surface markers (T1/ST2, IL-17RB, ICOS, CD45) and associated cytokines. In this study, these cells related genes or molecules in PBMC from patients with Graves' hyperthyroidism were measured, and the potential correlation between them was analyzed. The expression levels of T1/ST2, IL-17RB, ICOS, IL-5 and IL-13, which represented nuocytes associated molecules were significantly increased in patients, meanwhile, the RORα mRNA also had a tendency to increase. In addition, IFN-γ and T-bet (Th1 related cytokine and transcription factor) were obviously decreased, and there was a positive correlation between IL-17RB and IL-13. These results suggested that there were polarized nuocytes in Graves' hyperthyroidism patients, and which closely related to the down-regulation of Th1 cells or relatively advantage of Th2 differentiation.
| S-EPMC4270543 | biostudies-literature
Project description:IntroductionGraves' disease (Graves' hyperthyroidism) is a challenging condition for the young person and their family. The excess thyroid hormone generated by autoimmune stimulation of the thyroid stimulating hormone receptor on the thyroid gland can have a profound impact on well-being. Managing the young person with Graves' hyperthyroidism is more difficult than in older people because the side effects of conventional treatment are more significant in this age group and because the disease tends not to resolve spontaneously in the short to medium term. New immunomodulatory agents are available and the anti-B cell monoclonal antibody rituximab is of particular interest because it targets cells that manufacture the antibodies that stimulate the thyroid gland in Graves'.Methods and analysisThe trial aims to establish whether the combination of a single dose of rituximab (500 mg) and a 12-month course of antithyroid drug (usually carbimazole) can result in a meaningful increase in the proportion of patients in remission at 2 years, the primary endpoint. A single-stage, phase II A'Hern design is used. 27 patients aged 12-20 years with newly presenting Graves' hyperthyroidism will be recruited. Markers of immune function, including lymphocyte numbers and antibody levels (total and specific), will be collected regularly throughout the trial.DiscussionThe trial will determine whether the immunomodulatory medication, rituximab, will facilitate remission above and beyond that observed with antithyroid drug alone. A meaningful increase in the expected proportion of young patients entering remission when managed according to the trial protocol will justify consideration of a phase III trial.Ethics and dissemination The trial has received a favourable ethical opinion (North East - Tyne and Wear South Research Ethics Committee, reference 16/NE/0253, EudraCT number 2016-000209-35). The results of this trial will be distributed at international endocrine meetings, in the peer-reviewed literature and via patient support groups.Trial registration numberISRCTN20381716.
| S-EPMC6347892 | biostudies-literature