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BMJ Open Jun 2022The clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study,... (Observational Study)
Observational Study
OBJECTIVES
The clinical course of thyroid eye disease (TED) is heterogeneous and predicting patients who may develop the severe sequelae of the disease is difficult. In this study, we evaluated the longitudinal association between changes in serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb) levels and course of disease activity and severity over time.
DESIGN
This was a multicentre, prospective, observational study.
SETTING
Fifteen tertiary care oculoplastic service centres in Korea.
PARTICIPANTS
Seventy-six patients with newly diagnosed TED were included and followed up for 12 months.
METHODS
We evaluated clinical characteristics and serum TRAb levels at baseline, 6 and 12 months of TED diagnosis. Additionally, we analysed longitudinal associations between the serum TRAb levels and clinical activity score (CAS), no signs or symptoms, only signs, soft tissue involvement, proptosis, extraocular muscle involvement, corneal involvement, sight loss (NOSPECS) score and proptosis.
RESULTS
Thyroid-stimulating immunoglobulin (TSI) and TSH-binding inhibitory immunoglobulin (TBII) levels decreased during the 1-year follow-up, whereas disease activity measured using CAS decreased mainly in the first 6 months. Disease severity measured using NOSPECS score and proptosis remained unchanged. Moreover, inter-person differences in TBII levels were associated with CAS, NOSPECS score and proptosis over time, whereas inter-person differences in TSI levels were associated with NOSPECS score. Subgroup analysis of patients with a baseline CAS≥4 demonstrated that within-person changes in TSI levels affected the CAS and NOSPECS score.
CONCLUSIONS
Follow-up measurement of serum TSI and TBII levels may help evaluate TED prognosis and enable accurate clinical decision-making.
Topics: Autoantibodies; Graves Ophthalmopathy; Humans; Immunoglobulins, Thyroid-Stimulating; Immunologic Tests; Prospective Studies; Receptors, Thyrotropin
PubMed: 35728893
DOI: 10.1136/bmjopen-2021-050337 -
Frontiers in Endocrinology 2023The most frequent extrathyroidal Graves' disease manifestation is Graves' orbitopathy (GO). The treatment of GO is determined by its severity and activity. There is... (Review)
Review
The most frequent extrathyroidal Graves' disease manifestation is Graves' orbitopathy (GO). The treatment of GO is determined by its severity and activity. There is currently no reliable, impartial method for assessing it clinically or distinguishing fibrosis from active inflammatory disorders. Today, imaging methods including orbital ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) are frequently employed to show pathological abnormalities in the ocular adnexa of GO patients. In addition, a not widely accepted technique - 99mTc-DTPA SPECT - has some potential to evaluate retrobulbar inflammation in GO patients. However, FDG-PET/CT is possibly superior to other imaging modalities in detecting inflammation in GO and it may be useful in assessing disease activity in case of clinical or serological uncertainty. It might also act as an early indicator of GO development and its aggravation before irreversible tissue alterations take place and may be used in the differential diagnosis of inflammatory disorders of the orbit. However, before FDG-PET/CT could be applied in daily clinical practice, the methodology of GO activity assessment with defined cut-off values for radionuclide concentration - standardized units of value (SUV) have to be established and validated. In addition, the limitations of this technique have to be recognized.
Topics: Humans; Graves Ophthalmopathy; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Graves Disease; Inflammation
PubMed: 37600686
DOI: 10.3389/fendo.2023.1138569 -
Genes May 2023The risk of Graves' orbitopathy (GO) is related to the human leukocyte antigen (HLA) profile and was demonstrated to be increased in patients with elevated total...
The risk of Graves' orbitopathy (GO) is related to the human leukocyte antigen (HLA) profile and was demonstrated to be increased in patients with elevated total cholesterol (TC) and/or low-density lipoprotein (LDL) cholesterol. We hypothesized that there were some HLA alleles that were related to both GO and TC and/or LDL levels. Therefore, the aim of the study was to compare the TC/LDL results in patients in whom GO-related HLA alleles were present to those in whom they did not occur. HLA classes were genotyped using a next-generation sequencing method in 118 patients with Graves' disease (GD), including 63 and 55 patients with and without GO, respectively. Lipid profiles were assessed at the time of the GD diagnosis. A significant correlation between the presence of GO high-risk alleles ( and ) and higher TC/LDL levels was found. Additionally, the presence of alleles associated with non-GO GD ( and ), as well as alleles in linkage disequilibrium with (i.e., and ), was correlated with lower TC levels. These results further confirm the significance of TC/LDL in the risk of GO development and provide evidence that associations between TC/LDL and GO can be HLA-dependent.
Topics: Humans; Graves Ophthalmopathy; Graves Disease; HLA-DRB1 Chains; Proteins; Cholesterol; Lipids
PubMed: 37372389
DOI: 10.3390/genes14061209 -
Frontiers in Endocrinology 2023Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital...
BACKGROUND
Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis.
METHODS
Two distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections.
RESULTS
GO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation.
CONCLUSION
These results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.
Topics: Humans; Graves Ophthalmopathy; Myofibroblasts; Receptors, Thyrotropin; Intestinal Barrier Function; Toll-Like Receptor 5; Toll-Like Receptor 9; Graves Disease; Inflammation
PubMed: 38107520
DOI: 10.3389/fendo.2023.1173481 -
Turkish Journal of Ophthalmology Aug 2020To evaluate the effect of proptosis on choroidal thickness in patients with Graves' ophthalmopathy.
OBJECTIVES
To evaluate the effect of proptosis on choroidal thickness in patients with Graves' ophthalmopathy.
MATERIALS AND METHODS
Twenty-five eyes of 25 Graves' patients with proptosis, 25 eyes of 25 Graves' patients without proptosis, and 25 eyes of 25 healthy individuals were included in this prospective study. The subfoveal choroidal thickness and choroidal thicknesses at 6 points from the fovea at 500 μm intervals were measured by Cirrus HD-OCT. All measurements were compared among the proptosis, non-proptosis, and control groups and the active, inactive, and control groups.
RESULTS
The mean subfoveal choroidal thickness in the proptosis group was 289.7±68.5 μm, 322.5±55.8 μm in the non-proptosis group, and 316.1±63.0 μm in the control group. The mean nasal choroidal thickness was 260.5±63.5 μm in the proptosis group, 293.9±57.9 μm in the non-proptosis group, and 279.5±63.1 μm in the control group. The mean temporal choroidal thickness was 261.8±60.9 μm in the proptosis group, 289.0±51.8 μm in the non-proptosis group, and 287.8±56.2 μm in the control group. Mean choroidal thickness was 264.7±58.5 μm in the proptosis group, 296.2±47.5 μm in the non-proptosis group, and 288.3±55.1 μm in the control group. There were no statistically significant differences among the groups with respect to choroidal thickness measurements (p>0.05).
CONCLUSION
No significant difference in choroidal thickness was detected between Graves' patients with and without proptosis and the controls. There was no effect of clinical activation on choroidal thickness.
Topics: Adult; Choroid; Disease Progression; Exophthalmos; Female; Follow-Up Studies; Graves Ophthalmopathy; Humans; Male; Prospective Studies; Tomography, Optical Coherence
PubMed: 32854466
DOI: 10.4274/tjo.galenos.2020.97415 -
Endocrine Practice : Official Journal... Jul 2023Autoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using...
OBJECTIVE
Autoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using several immunoassays within an exploratory, controlled trial in patients with GD receiving a monoclonal antibody (mAb) targeting the neonatal crystallizable fragment receptor (FcRn).
METHODS
Serial measurements of TSH-R-Ab serum levels were performed using 3 different binding and cell-based assays in patients with GD either on medication or on placebo.
RESULTS
In contrast to the placebo group, in which no changes were observed, a 12-week mAb therapy led to an early and significant decrease (>60%) in the serum TSH-R-Ab levels in patients with thyroidal and extrathyroidal GD, as unanimously shown in all 3 assays. These marked changes were noted already at week 7 post baseline (P <.0001 for the binding immunoassay and for the luciferase (readout) bioassay). The 3 TSH-R-Ab binding and bioassays were highly correlated in the samples of both study groups (binding immunoassay vs luciferase bioassay, r =.91, P <.001, binding vs cyclic adenosine monophosphate (cAMP) bioassay, r = 0.86, P <.001, and luciferase vs cAMP bioassay, r = 0.71, P =.006). The serological results correlated with the course of the extrathyroidal clinical parameters of GD, that is, clinical activity score and proptosis.
CONCLUSION
Targeting the FcRn markedly reduces the disease-specific TSH-R-Ab in patients with GD. The novel and rapid TSH-R-Ab bioassay improves diagnosis and management of patients with GD.
Topics: Humans; Infant, Newborn; Antibodies, Monoclonal; Autoantibodies; Graves Disease; Immunoglobulins, Thyroid-Stimulating; Long-Acting Thyroid Stimulator; Receptors, Thyrotropin; Thyrotropin
PubMed: 37080298
DOI: 10.1016/j.eprac.2023.04.002 -
PloS One 2022Graves' ophthalmopathy (GO) is a complex inflammatory condition affecting the orbit and is often associated with Graves' disease (GD). This study aims to determine the...
Graves' ophthalmopathy (GO) is a complex inflammatory condition affecting the orbit and is often associated with Graves' disease (GD). This study aims to determine the levels of thyroid-stimulating immunoglobulin (TSI) and thyroid-stimulating hormone receptor autoantibody (TSHR-ab) in the serum of patients with GO, compare it with the GD, and determine whether there is a correlation with the clinical course of GO. The cross-sectional study included 82 patients with GO, 81 patients with GD, and 75 healthy subjects. The ocular manifestations of GO were identified and evaluated by the clinical activity score (CAS) and severity of GO using the European Group of Graves' Orbitopathy (EUGOGO). TSI and TSHR-ab levels in the serum of participants were determined with ELISA kits and correlated with clinical findings. A total of 238 participant's data were analyzed. There were 14 patients (17%) with unilateral GO. The most common ocular signs were eyelid retraction 68 (82.3%) and proptosis 61 (74.4%). The mean CAS score was 2.65±1.64 in GO patients and was higher in men than women (P = 0.008). The mean of TSI was 37.95±35.41 in GO, 14.16±15.67 in GD, and 4.33±2.94 in healthy controls (P<0.0001). The TSI was significantly higher in patients with GO than in those with GD (P<0.0001). There were no correlations between TSI and TSHR-ab levels and CAS scores. However, we observed a correlation between the TSI level and the severity of GO (P = 0.023). The area under the ROC curve (AUC) of TSI was 0.933 and selected 14.1 IU/ml was the optimal cutoff value (98.78% of sensitivity, 83.97% of specificity). Our study showed that TSI is significantly related to GO and the severity of GO. Therefore, TSI can be used as a predictor of severe GO to help in prognostication, follow-up and treatment planning.
Topics: Male; Animals; Humans; Female; Immunoglobulins, Thyroid-Stimulating; Graves Ophthalmopathy; Cross-Sectional Studies; Receptors, Thyrotropin; Graves Disease; Autoantibodies; Gerbillinae
PubMed: 36395261
DOI: 10.1371/journal.pone.0277055 -
Journal of Pediatric Endocrinology &... Oct 2016Risk of developing thyroid-associated ophthalmopathy (TAO) in children and adolescents is similar or may be even slightly higher than in adults. The aim of this article... (Review)
Review
BACKGROUND
Risk of developing thyroid-associated ophthalmopathy (TAO) in children and adolescents is similar or may be even slightly higher than in adults. The aim of this article is to review and summarize current knowledge regarding diagnostic and therapeutic measures in pediatric TAO.
CONTENT
MEDLINE and EMBASE papers were searched using the terms 'pediatric Graves' ophthalmopathy' 'pediatric Graves' orbitopathy', 'thyroid-associated ophthalmopathy in childhood and adolescence' from the year 1970 to December 2015.
SUMMARY
TAO usually accompanies hyperthyreosis in Graves' disease, but may also occur in patients with hypothyreosis due to chronic lymphocytic thyroiditis (Hashimoto's disease) or in euthyroid patients. Current information regarding epidemiology, pathogenesis, symptoms and treatment of TAO in children and adolescents is presented. The course of the disease is usually mild, eye disturbances often regress after restoring euthyroidism and a 'wait and see' policy is appropriate in the majority of patients. In rare cases, sight-threatening complications [dysthyroid optic neuropathy (DON) or corneal breakdown] may develop and immediate surgical intervention might become necessary.
OUTLOOK
Close cooperation between pediatric endocrinologists and opthalmologists is extremely important to ensure best care and quality of life in patients with thyroid gland dysfunction. Further investigations on pathogenesis and course of TAO in children and adolescents should be performed for better management of this disease in this group of patients.
Topics: Adolescent; Adult; Child; Graves Ophthalmopathy; Humans
PubMed: 27682712
DOI: 10.1515/jpem-2016-0122 -
Frontiers in Endocrinology 2023To analyze the efficacy of mycophenolate mofetil (MMF) and glucocorticoid administration in patients with thyroid-associated ophthalmopathy (TAO).
OBJECTIVE
To analyze the efficacy of mycophenolate mofetil (MMF) and glucocorticoid administration in patients with thyroid-associated ophthalmopathy (TAO).
METHODS
Sixty patients with moderate to severe TAO treated in Jingzhou Central Hospital from January 2022 to June 2022 were selected and enrtolled in this study. The subjects were divided into experimental group (n=30) and control group (n=30) based on the random number table method. Glucocorticoid pulse therapy was provided in the control group, while MMF was given in the experimental group on the basis of Control group. Clinical activity score (CAS), quality of life (QOL), visual acuity, eyelid fissure width, intraocular pressure, and degree of exophthalmos were observed at the time of admission and at the 12 week and 24 post-treatment weeks. We compared the immune function (TRAb, IL-6, and CD4+/CD8+) of the two groups pre-treatment and 24 weeks post-treatment, and evaluated the clinical therapeutic effect.
RESULTS
The clinical effective rates at 12 and 24 weeks in the experimental group were higher (73.3% and 83.3%) than those in the control group (46.7% and 60.0%) (0.05). After 12 weeks of treatment, patients' CAS scores, and bilateral lid fissure width decreased and right eye visual acuity increased in the control group compared with those before treatment ( 0.05); further, after 24 weeks of treatment, patients' QOL scores and bilateral visual acuity increased and CAS scores, bilateral lid fissure width and proptosis decreased compared with those before treatment, and patients' QOL scores, CAS scores and bilateral proptosis improved more than those at 12 weeks of treatment (0.05). Additionally, greater improvements were observed in the patients' QOL and CAS scores, and proptosis after 24-week treatment than after 12-week treatment (<0.05). In the experimental group, the QOL score and binocular visual acuity increased, whereas the CAS score, intraocular pressure, lid width, and proptosis decreased after 12 weeks of treatment as compared to the values of these parameters in the pre-treatment period ( 0.05); after 24 weeks of treatment, greater improvements were established in the ocular-related indexes improved compared to the pre-treatment period and after 12 weeks of treatment ( 0.05). After 12 weeks of treatment, the patients in the experimental group had more considerable improvements in the right visual acuity, right intraocular pressure, and left lid fissure width than the control group ( 0.05); at 24 weeks of treatment, patients in the experimental group had greater improvements in the QOL score, bilateral visual acuity, intraocular pressure, bilateral lid fissure width, and bilateral proptosis than the control group ( 0.05). No significant differences were found in the values of TRAb, IL-6, and CD4+/CD8+ between the two groups before treatment (>0.05); the values of TRAb, IL-6, and CD4+/CD8+ in the experimental group was significantly lower than those before treatment and in the control group after 24weeks of treatment. (>0.05). No statistically significant difference was observed in the incidence of liver damage and menstrual disorders between the two groups during the 24 weeks of treatment (>0.05).
CONCLUSION
The combination of oral MMF and glucocorticoid shock therapy is an effective drug for the treatment of patients with moderately active TAO.
Topics: Humans; Glucocorticoids; Graves Ophthalmopathy; Mycophenolic Acid; Quality of Life; Interleukin-6; Exophthalmos; Treatment Outcome
PubMed: 37025403
DOI: 10.3389/fendo.2023.1140196 -
PloS One 2020We propose a new method to calculate proptosis by using the simple Heron's formula and analyze its feasibility. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
We propose a new method to calculate proptosis by using the simple Heron's formula and analyze its feasibility.
METHOD
It was a none-inferiority trial. The registration number was ChiCTR1900026490. The absolute value of proptosis in 120 eyes, 60 patients without eye injury or diseases, was measured by computed tomography (CT) and simple Heron's formula. We did regression analysis and analyzed the differences between the two methods with Medcalc software version 19.0.4. The result was showed by Passing-Bablok regression analysis diagram and Bland and Altman plot.
RESULTS
The Passing-Bablok showed that the result of proptosis measured by CT and simple Heron's formula showed good positive correlation. A 95% limit of agreement in proptosis between CT and Heron's formula method was -0.46 to 0.54 mm in right eye and -0.45 to 0.46 mm in left eye. 1.66% (1/60) point was outside 95% LoA in both eyes. Moreover, a 95% limit of agreement between CT and Heron's formula method was -0.42 to 0.56 mm in difference of both eyes. 3.33% (2/60) points were outside 95% LoA. The points in all Bland and Altman plots were lower than 5%. It means that the results of comparison between the two methods had a good consistency in the measurement of proptosis.
CONCLUSIONS
Heron's formula could be applied to calculate proptosis and has a good consistency compared with computed tomography (CT). This method is practical in proptosis assessment because of its accuracy, reliability and simplicity.
Topics: Adult; Anthropometry; Exophthalmos; Eye; Feasibility Studies; Female; Humans; Male; Middle Aged; Reproducibility of Results; Tomography, X-Ray Computed; Young Adult
PubMed: 32480401
DOI: 10.1371/journal.pone.0234016