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American Journal of Ophthalmology Case... Dec 2023We report an unusual case of severe proptosis during phacoemulsification in a 58-year-old female with a history of Crohn's disease, bilateral chronic panuveitis, prior...
PURPOSE
We report an unusual case of severe proptosis during phacoemulsification in a 58-year-old female with a history of Crohn's disease, bilateral chronic panuveitis, prior bilateral central retinal vein occlusion, and uncontrolled steroid-associated ocular hypertension requiring bilateral Ahmed glaucoma drainage device (GDD) implantation with pars plana tube placement.
OBSERVATIONS
During phacoemulsification of the right eye, the patient developed significant proptosis. Following lid speculum removal and mechanical eyelid manipulation, the proptosis resolved within 20 minutes without requiring a lateral canthotomy. The patient had no permanent visual complications.
CONCLUSIONS AND IMPORTANCE
The likely pathophysiology of intraoperative proptosis in this case was accumulation of fluid in the retrobulbar space due to a functioning Ahmed tube shunt with the tube placed in the vitreous cavity. To avoid this complication, concurrent cataract surgery may be considered for patients with pars plana tube placement GDD surgery.
PubMed: 37554298
DOI: 10.1016/j.ajoc.2023.101901 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023Thyroid-associated ophthalmopathy (TAO) is a multifactorial-mediated autoimmune orbital disease with the highest incidence of orbital disease in adults. Due to the...
Thyroid-associated ophthalmopathy (TAO) is a multifactorial-mediated autoimmune orbital disease with the highest incidence of orbital disease in adults. Due to the complex clinical manifestations and prolonged course,TAO seriously affect the physical and mental health of patients.The pathogenesis of TAO has not been fully elucidated and the treatment lacks specificity. Therefore, in-depth research on the pathogenesis of TAO is to find effective treatments. In recent years, studies have suggested that there is gut microbiota disorder in TAO, and the risk factors of TAO can promote gut microbiota disorder. Disordered gut microbiota can participate in the occurrence and development of TAO via influencing T cell differentiation, mimicking autoantigens, and influencing host non-coding RNA expression. Modulating the gut microbiota also has therapeutic effects on TAO and is a promising therapeutic approach.
Topics: Adult; Humans; Graves Ophthalmopathy; Gastrointestinal Microbiome; Orbital Diseases; Autoimmune Diseases; Cell Differentiation
PubMed: 38432867
DOI: 10.11817/j.issn.1672-7347.2023.230187 -
International Journal of Molecular... Nov 2023Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory... (Review)
Review
Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves' disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs' functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD.
Topics: Humans; T-Lymphocytes, Regulatory; Genome-Wide Association Study; Graves Disease; Hashimoto Disease; Receptors, Thyrotropin
PubMed: 38003622
DOI: 10.3390/ijms242216432 -
Autoimmunity Reviews May 2024Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves'... (Review)
Review
Thyroid eye disease (TED) is an autoimmune condition affecting the orbit and the eye with its adnexa, often occurring as an extrathyroidal complication of Graves' disease (GD). Orbital inflammatory infiltration and the stimulation of orbital fibroblasts, triggering de novo adipogenesis, an overproduction of hyaluronan, myofibroblast differentiation, and eventual tissue fibrosis are hallmarks of the disease. Notably, several redox signaling pathways have been shown to intensify inflammation and to promote adipogenesis, myofibroblast differentiation, and fibrogenesis by upregulating potent cytokines, such as interleukin (IL)-1β, IL-6, and transforming growth factor (TGF)-β. While existing treatment options can manage symptoms and potentially halt disease progression, they come with drawbacks such as relapses, side effects, and chronic adverse effects on the optic nerve. Currently, several studies shed light on the pathogenetic contributions of emerging factors within immunological cascades and chronic oxidative stress. This review article provides an overview on the latest advancements in understanding the pathophysiology of TED, with a special focus of the interplay between oxidative stress, immunological mechanisms and environmental factors. Furthermore, cutting-edge therapeutic approaches targeting redox mechanisms will be presented and discussed.
Topics: Humans; Oxidation-Reduction; Graves Ophthalmopathy; Oxidative Stress; Animals; Cytokines; Signal Transduction; Autoimmune Diseases
PubMed: 38527685
DOI: 10.1016/j.autrev.2024.103534 -
Scientific Reports Nov 2023Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated....
Although antithyroid drug (ATD)-induced agranulocytosis is a significant concern, its risks associated with long-term use and re-administration are not fully elucidated. Therefore, we performed this study to determine the incidence of ATD-induced leukopenia and G-CSF administration using administrative claims database. Retrospective cohort study. This study was performed using the DeSC Japanese administrative claims database. A total of 12,491 patients with newly diagnosed Graves' disease (GD) who received methimazole or propylthiouracil between April 2014, and February 2021 among 3.44 million patients in the database were included in the study. We measured the six-year incidence of leukopenia and granulocyte colony-stimulating factor (G-CSF) administration. The incidence of leukopenia and G-CSF administration was 1.34% (168 patients) and 0.30% (38 patients), respectively. Leukopenia had a dose-dependent and biphasic incidence. The incidence of leukopenia and G-CSF administration was 37.2 (0.7%) and 8.0 (0.2%) per 1000 person-years during the first 72 days of ATD initiation, whereas it was 3.1 and 0.7 per 1000 person-years during the subsequent 6 years, respectively. The incidence of both outcomes was comparable between first administration and re-administration of ATD. The incidence of ATD-induced leukopenia and G-CSF administration was high in the first 72 days, with a reduced risk for at least 6 years thereafter. The incidence was similar between first administration and re-administration. ATD, a standard therapy, is often administered for a long period; therefore, our findings can guide the treatment of GD.
Topics: Humans; Antithyroid Agents; Cohort Studies; Retrospective Studies; Graves Disease; Neutropenia; Granulocyte Colony-Stimulating Factor; Thrombocytopenia
PubMed: 37935745
DOI: 10.1038/s41598-023-46307-5 -
European Thyroid Journal Feb 2024Mood disorders are common in Graves' disease despite treatment. The pathogenic mechanisms involved are unknown and so is whether previous psychiatric disease influences...
BACKGROUND
Mood disorders are common in Graves' disease despite treatment. The pathogenic mechanisms involved are unknown and so is whether previous psychiatric disease influences these symptoms.
METHODS
This is a longitudinal study conducted in Sweden on 65 women with newly diagnosed Graves' disease and 65 matched controls. Participants were examined during hyperthyroidism and after 15 months of treatment. Examinations included blood sampling, and psychiatric testing with the Comprehensive Psychopathological Rating Scale for Affective Syndromes and the Structured Clinical Interview for DSM-IV - Axis I Disorders. We also performed two analyses of a national population-based registry to determine previous psychiatric diagnoses and previous prescriptions of psychoactive drugs in (i) all patients we asked to participate and (ii) all Swedish women given a diagnosis of hyperthyroidism during 2013-2018, comparing them to matched controls.
RESULTS
There was no increased previous psychiatric comorbidity in Graves' patients compared to controls. There was no higher prevalence of psychiatric diagnoses and prescriptions of psychoactive drugs between (i) included GD patients compared to those who declined participation and (ii) women with a hyperthyroidism diagnosis in 5 years prior to their diagnosis, compared to matched controls. Depression scores and anxiety scores were higher in patients compared to controls both during hyperthyroidism (depression (median (IQR): 7.5 (5.0-9.5) vs 1.0 (0.5-2.5) P < 0.001), anxiety: 7.7 (5.0-11) vs 2.5 (1.0-4.0) P < 0.001) and after treatment (depression: 2.5 (1.5-5.0) vs 1.5 (0.5-3.5) P < 0.05), anxiety: 4.0 (2.5-7.5) vs 3.0 (1.5-5.0) P < 0.05). Patients with a previous psychiatric condition, mild eye symptoms, and a younger age had more anxiety at 15 months compared to patients without these symptoms and a higher age (all p<0.05).
CONCLUSION
Graves' disease affects patients' mood despite treatment. A previous psychiatric condition, mild eye symptoms, and a younger age increase the vulnerability for long-lasting symptoms and require specific attention.
Topics: Humans; Female; Infant; Longitudinal Studies; Graves Disease; Hyperthyroidism; Mood Disorders; Psychotropic Drugs
PubMed: 38215285
DOI: 10.1530/ETJ-23-0247 -
Endocrine Aug 2023The pathogenesis of Graves' orbitopathy/thyroid-associated orbitopathy (TAO) is still unclear, and abnormal DNA methylation in TAO has been reported. Thus, selecting and...
PURPOSE
The pathogenesis of Graves' orbitopathy/thyroid-associated orbitopathy (TAO) is still unclear, and abnormal DNA methylation in TAO has been reported. Thus, selecting and exploring TAO biomarkers associated with DNA methylation may provide a reference for new therapeutic targets.
METHODS
The TAO-associated expression data and methylation data were downloaded from The Gene Expression Omnibus database. Firstly, weighted gene co-expression network analysis was used to obtain the TAO-related genes, which were intersected with differentially methylated genes (DMGs), and differentially expressed genes between TAO samples and normal samples to obtain TAO-associated DMGs (TA-DMGs). Thereafter, the functions of the TA-DMGs were analyzed, and diagnostic markers were screened by least absolute shrinkage and selection operator (Lasso) regression analysis and support vector machine (SVM) analysis. The expression levels and diagnostic values of the diagnostic markers were also analyzed. Furthermore, single gene pathway enrichment analysis was performed for each diagnostic marker separately using gene set enrichment analysis (GSEA) software. Next, we also performed immune infiltration analysis for each sample in the GSE58331 dataset using the single-sample GSEA algorithm, and the correlation between diagnostic markers and differential immune cells was explored. Lastly, the expressions of diagnostic markers were explored by quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS
A total of 125 TA-DMGs were obtained. The enrichment analysis results indicated that these TA-DMGs were mainly involved in immune-related pathways, such as Th1 and Th2 cell differentiation and the regulation of innate immune response. Moreover, two diagnostic markers, including S100A11 and NKD2, were obtained by Lasso regression analysis and SVM analysis. Single gene pathway enrichment analysis showed that S100A11 was involved in protein polyufmylation, pancreatic-mediated proteolysis, and NKD2 was involved in innate immune response in mucosa, Wnt signaling pathway, etc. Meanwhile, immune cell infiltration analysis screened 12 immune cells, including CD56 dim natural killer cells and Neutrophil cells that significantly differed between TAO and normal samples, with the strongest positive correlation between NKD2 and CD56 dim natural killer cells. Finally, the qRT-PCR illustrated the expressions of NKD2 and S100A11 between normal and TAO.
CONCLUSION
NKD2 and S100A11 were screened as biomarkers of TAO and might be regulated by DNA methylation in TAO, providing a new reference for the diagnosis and treatment of TAO patients.
Topics: Humans; Graves Ophthalmopathy; Algorithms; Cell Differentiation; Machine Learning; Calcium-Binding Proteins; Adaptor Proteins, Signal Transducing
PubMed: 37059863
DOI: 10.1007/s12020-023-03349-z -
Frontiers in Immunology 2023Hypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between...
BACKGROUND
Hypothyroidism and hyperthyroidism are observationally associated with rheumatoid arthritis (RA), but causality is unclear. To evaluate the causal relationship between thyroid function and RA, we conducted a two-Sample bidirectional Mendelian Randomization (MR) study.
METHODS
Single nucleotide polymorphisms associated with six phenotypes were selected from the FinnGen biobank database, The ThyroidOmics Consortium database, and the IEU Open GWAS database. For the forward MR analysis, we selected hypothyroidism (N=213,390), Graves' disease (GD) (N=199,034), other types of hyperthyroidism (N=190,799), free thyroxine (FT4, N=49,269), and thyroid-stimulating hormone (TSH, N=54,288) as the five related thyroid function phenotypes for exposure, with RA (N=58,284) as the outcome. Reverse MR analysis selected RA as the exposure and five phenotypes of thyroid function as the outcome. The Inverse variance weighting (IVW) method was used as the primary analysis method, supplemented by weighted median (WM) and MR-Egger methods. Cochran's Q test, MR-PRESSO, MR-Egger regression methods, and leave-one-out analysis were employed to assess sensitivity and pleiotropy.
RESULTS
Forward MR evidence indicates that genetic susceptibility to hypothyroidism is associated with an increased risk of RA (OR=1.758, P=7.61×10). Reverse MR evidence suggests that genetic susceptibility to RA is associated with an increased risk of hypothyroidism (OR=1.274, P=3.88×10), GD (OR=1.269, P=8.15×10), and other types of hyperthyroidism (OR=1.141, P=1.80×10). There is no evidence to support a forward or reverse causal relationship between genetic susceptibility to RA and FT4, TSH.
CONCLUSION
Our results provide genetic evidence supporting bidirectional causal relationships between thyroid function and RA. These findings inform preventive strategies and interventions targeting RA and thyroid dysfunction.
Topics: Humans; Mendelian Randomization Analysis; Hyperthyroidism; Hypothyroidism; Arthritis, Rheumatoid; Graves Disease; Genetic Predisposition to Disease; Thyrotropin
PubMed: 38090574
DOI: 10.3389/fimmu.2023.1238757 -
Frontiers in Endocrinology 2023We aimed to explore the frequencies of islet β-cell autoantibodies and insulin resistance (IR) in thyroid-associated ophthalmopathy (TAO) and identify specific diabetes...
BACKGROUND
We aimed to explore the frequencies of islet β-cell autoantibodies and insulin resistance (IR) in thyroid-associated ophthalmopathy (TAO) and identify specific diabetes mellitus (DM) indicators as early predictors for dysthyroid optic neuropathy (DON).
METHODS
Ninety-eight TAO patients (57 DON and 41 non-DON patients) and 48 healthy control (HC) participants were recruited for this prospective cross-sectional study. Serum thyroxine, serum thyroid autoantibodies, serum humoral immune markers against islet β-cell, fasting plasma glucose (FPG), fasting serum insulin (FINS), fasting c-peptide (FCP), and glycosylated hemoglobin A1 (HbA1c) were measured. Logistic regression analysis was used to evaluate the correlation of patients' age, body mass index (BMI), FPG, HbA1c, and related indexes of islet β-cell function to the occurrence of DON.
RESULTS
The DON group had higher FPG (P<0.001, 0.016) and HbA1c (P<0.0001, P<0.001) levels than the HC and non-DON groups. The homeostasis model assessment (HOMA)-IR level was the highest in the DON group (HC 2.15 ± 0.89, non-DON 2.41 ± 1.24, and DON 2.82 ± 2.65), while the HOMA-β level was the lowest (HC 101.8 ± 44.75%, non-DON 102.9 ± 54.61%, and DON 88.29 ± 52.75%), with no significant differences (P=1, P>0.05). On univariate analysis, age (P=0.006), BMI (P=0.022), history of steroid use (P=0.014), FPG (P=0.013), and HbA1c (P=0.001) levels were significantly associated with the presence/absence of DON. In addition, after adjusting for potential confounds, the HbA1c level was an independent factor associated with DON (P=0.009, OR=4.012).
CONCLUSIONS
HbA1c is an independent risk factor for DON. Given the interconnected link between thyroid dysfunction and DM, the use of HbA1c as a potential biomarker for DON warrants further investigation.
Topics: Humans; Glycated Hemoglobin; Cross-Sectional Studies; Prospective Studies; Risk Factors; Insulin Resistance; Diabetes Mellitus; Graves Ophthalmopathy; Optic Nerve Diseases; Autoantibodies
PubMed: 37881496
DOI: 10.3389/fendo.2023.1251209 -
Ophthalmic Plastic and Reconstructive...The authors report 4 cases of cutaneous hypersensitivity reactions developing in the course of teprotumumab treatment for thyroid eye disease. The onset of the cutaneous...
The authors report 4 cases of cutaneous hypersensitivity reactions developing in the course of teprotumumab treatment for thyroid eye disease. The onset of the cutaneous hypersensitivity reaction was also observed during the treatment course in all cases, between the second and fifth infusions. Teprotumumab-related cutaneous reactions suggest a possible immunogenic component of the monoclonal antibody and highlight the importance of close monitoring during treatment.
Topics: Humans; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Graves Ophthalmopathy
PubMed: 37656913
DOI: 10.1097/IOP.0000000000002482