Graves' Disease Patients Research Articles

Inclusion of ALKBH5 as a candidate gene for the susceptibility of autoimmune thyroid disease

PurposeRNA demethylase AlkB homolog 5 (ALKBH5) gene is pivotal in N6-methyladenosine (m6A) modification. Therefore, this study aimed to explore the potential relationship between polymorphisms of ALKBH5 gene and the development of autoimmune thyroid disease (AITD). Material and methodsA case-control study of 979 AITD patients, including 620 Graves' disease (GD) and 359 Hashimoto's thyroiditis (HT), and 732 normal controls of the Chinese Han population was performed using high-throughput sequencing (HiSeq) genotyping method for detecting 5 variants in ALKBH5 gene (rs12936694, rs2124370, rs4925144, rs8068517, and rs9913266). In addition, the associations between ALKBH5 single nucleotide polymorphisms (SNPs) and clinical phenotypes of AITD were investigated. ResultsCompared to normal controls, rs9913266 displayed significant differences in allele and genotype distributions in AITD and GD. rs12936694 also showed significantly different frequencies of alleles in AITD and GD. The link of these 2 loci polymorprhisms to AITD and GD also existed after adjusting for age and gender. When stratified by sex, the minor allele of rs9913266 was associated with the risk of female AITD and HT development before and after adjusting for age and gender. There was a significant association between rs8068517 locus and GD in females after adjusting for the confounders. Finally, we observed significant correlations of haplotypes CGACA and CAGCG to the susceptibility of AITD and GD. ConclusionsOur results provided evidence of association of polymorphisms in ALKBH5 gene with AITD, GD, and HT patients, and hence ALKBH5 might be the candidate gene for susceptibility to AITD.

Influence of high tissue-absorbed dose on anti-thyroid antibodies in radioiodine therapy of Graves' disease patients.

The results of radioactive iodine (RAI) treatment for Graves' disease (GD) are related to the choice of diagnostic and dosimetry protocols, the steroid protection used, and the subsequent 131I dose. The effect of a high tissue-absorbed dose on the level of anti-thyroid antibodies (ATA) has been rarely considered. To estimate the effect of the first RAI therapy with a dose of 250 Gy on anti-thyreoperoxidase (anti-TPO) and anti-thyroid-stimulating hormone (TSH) receptor thyrotropin receptor antibody - TRAb levels in GD patients. The analysis encompassed 46 consecutive patients with clinical presentation of GD. We examined the serum levels of TSH, free thyroxine (FT4), anti-TPO, TRAb, thyroid volume (ThV), 131I effective half-life (EHL), introduction of steroid protection, levothyroxine dose used in thyroid replacement therapy - TRT, and effectiveness of treatment. As a result of RAI treatment, hypothyroidism was found in 35 patients (76.1%), euthyroidism in 7 patients (15.2%) and hyperthyroidism in 4 patients (8.7%). After RAI, we observed ThV reduction and increased anti-TPO (p = 0.001 and p = 0.001, respectively). It was found that a shorter EHL correlated with a higher baseline TRAb concentration and lower final anti-TPO serum concentration (p = 0.03 and p = 0.01, respectively). Lower final TRAb was found in patients with steroid protection (p = 0.049). Intergroup comparison of patients without steroid protection showed significantly higher final anti-TPO concentation (p = 0.02). Intergroup comparison of patients with TRT revealed significantly higher final anti-TPO concentration (p = 0.04). The application of a high absorbed dose of 250 Gy in GD resulted in high efficacy of RAI therapy at 1-year follow-up. An increased ATA level and its relationships with EHL and ThV reduction were observed at 1-year follow-up. There is a possible relationship between steroid protection and anti-TPO concentration.

Graves' Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study.

BackgroundThe frequent coexistence of Graves’ disease (GD) and rheumatoid arthritis (RA) has been cited and discussed in observational studies, but it remains a question as to whether there is a causal effect between the two diseases.MethodsWe retrieved genome-wide association study (GWAS) summary data of GD and RA from BioBank Japan (BBJ). Single nucleotide polymorphisms (SNPs) associated with diseases of interest were selected as instrumental variables (IVs) at a genome-wide significance level (P < 5.0 × 10−8). The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. The horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. The statistical power of our MR result was calculated according to Brion’s method.ResultsOur study discovered a bidirectional causal effect between GD and RA. The presence of RA may increase the risk of GD by 39% (OR 1.39, 95% CI 1.10–1.75, P = 0.007). Similarly, the existence of GD may increase the risk of RA by 30% (OR 1.30, 95% CI 0.94–1.80, P = 0.112). Our study provides 100% power to detect the causal effect of RA on GD risk, and vice versa.ConclusionsWe found a bidirectional causal effect between GD and RA in an Asian population. Our study supported the clinical need for screening GD in RA patients, and vice versa. The potential benefit of sound management of RA in GD patients (or GD in RA patients) merits excellent attention. Moreover, novel satisfactory medicine for RA may be applicable to GD and such potential is worthy of further investigation.

A higher cut-off for Thyroid-stimulating immunoglobulin (TSI) could better predict relapse in Graves’ disease?

Background: TSH receptor (TSHr)-stimulating immunoglobulins (Igs) can be used as diagnostic markers of Graves’ disease (GD). Thyroid-stimulating immunoglobulin (TSI) assays exclusively detect these specific Igs. Materials and Methods: This was a prospective longitudinal study in which hyperthyroid patients with GD and toxic nodular goitres were evaluated at diagnosis. GD patients were also evaluated at antithyroid drug (ATD) withdrawal. An automated chemiluminescent assay measured TSI. According to the manufacturer TSI less than 0.55 IU/L was a non-reactive result. The authors evaluated the Se and Sp of the cutoff point provided by the TSI assay manufacturer, and tested other cutting points through a ROC curve, to assess relapse risk of Graves’ disease. Results: At diagnosis, were evaluated 92 (85.2%) GD patients aged 41.2 ± 2.0 years, and 16 patients (14.8%) with toxic multinodular goiter (TMNG) or toxic adenoma (TA), aged 60.8 ± 4.8 years. They were re-evaluated after 18 ± 4 months with methimazole (MMI) treatment. The follow-up after treatment suspension was of 20 ± 6 months. At diagnosis, the TSI (Se) and (Sp) were 98.9% and 100%, respectively. At ATD withdrawal, despite a high Se (95.5%), Sp was low (59.6%). By adjusting the cut-off to 1.11 (TSI &lt;1.11 IU/L non-reactive), TSI presented the best Sp (89.4%) with a small decrease in Se (93.3%) in predicting GD relapse. Conclusions: TSI had high Se and Sp in GD differential diagnosis with nodular goiters. In the assessment for GD relapse, by raising the cutting point to 1.11 IU/L, a better Sp was obtained at the expense of a small drop in Se. A larger sample is needed to support a higher TSI cut-off point in the clinical routine to assess GD relapse after ATD.

Immune reconstitution inflammatory syndrome-associated Graves disease in HIV-infected patients: clinical characteristics and response to radioactive iodine therapy.

We aimed to describe the clinical characteristics and the response to radioactive iodine (RAI) treatment of immune reconstitution inflammatory syndrome-associated Graves disease (IRIS-GD) in comparison to Graves disease (GD) seen in HIV-uninfected patients. We retrospectively reviewed the medical records of patients treated with RAI for GD. We obtained clinical, biochemical and HIV-related information of patients from their medical records. We compared patient characteristics and response to RAI treatment between patients with IRIS-GD and GD seen in HIV-uninfected patients. A total of 253 GD patients, including 51 patients with IRIS-GD, were included. Among IRIS-GD patients, CD4 cell nadir was 66 cells/µL (range:37-103) with a peak HIV viral load of 60900 copies/mL (range:36542-64500). At the time of diagnosis of IRIS-GD, all patients had a completely suppressed HIV viraemia with a CD4 cell count of 729 cells/µL (range:350-1279). The median interval between the commencement of HIV treatment and the onset of GD was 63months. At 3months follow-up, the proportion of patients with IRIS-GD achieving a successful RAI treatment outcome (euthyroid/hypothyroid state) was lower than that of HIV-uninfected patients (35.3% vs. 63.4%, respectively; p<0.001). The response rate remained lower (60.8%) among patients with IRIS GD than among HIV-uninfected GD patients (80.2%, p=0.004) at 6months follow-up. After correcting for differences in age, gender and pre-treatment thyroid-stimulating hormone level, there was no significant difference in RAI treatment response between the two groups. After correcting for possible confounders, the response to RAI treatment was not different between patients with IRIS-GD and GD in HIV-uninfected patients.

Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves’ disease and predictors of responsiveness to methimazole

BackgroundAs thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (Immulite™ TSI assay) in GD patients and compared it to the third generation thyroid-stimulating hormone receptor antibody (TRAb) electrochemiluminescence assay (Elecsys Anti-TSHR assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored. MethodsThis study involved 324 subjects, comprising patients with untreated GD (GD-UT), Graves’ ophthalmopathy (GO) patients, GD patients who had been treated for > 12 months (GD-T), autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). The Immulite™ TSI and Elecsys Anti-TSHR assay were performed on all samples. According to their responsiveness to methimazole, the GD-UT patients were divided into rapid and slow responder groups, and their clinical characteristics were compared. ResultsA receiver operating characteristic (ROC) curve analysis of GD-UT patients showed that the optimal TSI cut-off value was 0.57 IU/L. Logistic regression revealed that age and initial FT4 and TSI levels in the middle-dose methimazole group were related to a rapid response, while the initial FT4 level, but not TSI, in the high-dose group was also associated with a rapid response. ConclusionsThe clinical diagnostic performance of the Immulite™ TSI assay for diagnosing GD was comparable to that of the Elecsys Anti-TSHR assay. The initial FT4 and TSI levels can be used as predictors of the responsiveness to methimazole in patients with newly diagnosed GD.

Predisposition to Graves' disease and Graves' ophthalmopathy by genetic variants of IL2RA.

Previous studies have identified that Th17/Treg cells were involved in the occurrence and development of Graves' disease (GD). This study aimed at clarifying the association between GD susceptibility and nine single nucleotide polymorphisms (SNPs) of Th17/Treg cell-related genes, including IL2RA, miR27a, miR182, and FoxO1. A two-stage association study was performed in 650 GD patients and 1300 healthy controls. PCR-RFLP assays, real-time PCR, and ELISA were performed. In the first stage, association analysis has identified that IL2RA/rs3118470 TT genotype (Pc = 0.027, OR = 1.688) and IL2RA/rs2104286 AA genotype (Pc = 0.027, OR = 1.658) has significantly increased frequencies in patients with GD than control subjects. In the second stage, the result of rs2104286 was consistent with the first-stage results (AA genotype: Pc = 0.006, OR = 1.618). The combined data showed that IL2RA/rs2104286 AA genotype had increased frequencies in patients with GD (Pc = 8.772 × 10-6, OR = 1.636). Stratification analysis also revealed that rs2104286 AA genotype was significantly associated with Graves' ophthalmopathy (GO) susceptibility (Pc = 9.150 × 10-4, OR = 1.851). Functional studies showed that carriers of the rs2104286 AA genotype had lower IL2RA mRNA expression than AG genotype carriers (P = 0.021). Cytokine analyses revealed that the rs2104286 AA genotype individuals had lower IL-10 levels (P = 0.015) and increased IL-17 levels than AG genotype carriers (P = 1.467 × 10-4). In conclusion, our findings suggested that IL2RA/rs2104286 was associated with GD and GO susceptibility in Southwest Chinese Han population, which may be involved in the occurrence of GD and GO by affecting the mRNA expression of IL2RA gene and the cytokine production. KEY MESSAGES: We identified that IL2RA/rs2104286 locus contributed to the predisposition of Graves' disease (GD) and Graves' ophthalmopathy (GO). Functional analyses suggested that IL2RA/rs2104286 may participate in the occurrence of GD and GO by affecting the mRNA expression of IL2RA and cytokine (IL-10 and IL-17) secretion. We found that IL2RA (rs3118470, rs7093069), miR27a/rs895819, miR182/rs76481776, and FoxO1 (rs2297626, rs17592236, rs9549241, rs12585277) loci polymorphisms were not associated with GD susceptibility.

Relapse Rate and Clinical Risk Factors Affecting the Treatment of Graves’ Disease

Objective: To determine the relapse rate of Graves’ disease (GD) and identify important clinical risk factors for relapse.Materials and Methods: This was a 10-year retrospective cohort study. Information was collected with ICD10 E050 codes for Graves’ hyperthyroidism among Thai patients of both sexes and all ages with no history of pregnancy, thyroid storm or antithyroid drug (ATD) allergy.Results: The 286 included GD patients had a relapse rate of 35% after ATD withdrawal for one year. The clinical risk factors associated with relapse were male sex (p = 0.014), smoking (p = 0.001), serum free T4 (FT4) levels &gt; 2 times the upper normal range at diagnosis (p = 0.005), duration for maintenance treatment &lt; 6 and 9 months (p &lt; 0.005) compared with remission. A TSH level &lt; 1 mIU/L (p = 0.060) and MMI &gt; 2.5 mg per day before ATD withdrawal (p = 0.094) trended toward associations with relapse. The clinical factors that predicted GD relapse were serum FT4 levels at diagnosis (p = 0.006) and serum free T3 (FT3) levels before ATD withdrawal (p = 0.019).Conclusion: Male sex, smoking and serum FT4 levels at diagnosis &gt; 2 times the normal range were significant clinical factors for GD relapse in Thai patients. To reduce the relapse rate in the first year, MMI should be used in maintenance periods for 9 to 12 months with serum FT3 levels within low-normal ranges before ATD withdrawal. This would promote future guidelines for GD management in Thailand.

Predictive factors for recurrence in patients with Graves’ Disease following treatment with methimazole

Graves’ disease (GD) contributes for 60–80% of all hyperthyroidism. Methimazole is the first line drug and most commonly used as antithyroid drug (ATD). However, the relapse rate following ATD therapy is 40–50%. The aimed of this study was to evaluate long-term ATD treatments and to identify prognostic factors that contribute to GD recurrence. A total of 46 GD patients who referred to the Endocrinology Clinic, Dr. Sardjito General Hospital, Yogyakarta between January 2016 and December 2018 with thyrotropin receptor antibody (TRAb) tested and treated with methimazole were included in this study. Size of goiter was measured based on WHO grading system and eye syndrome based on NOSPEC score system. Patients were classified into recurrence and remission groups based on TRAb evaluation at 12 month following treatment. Result of thyroid hormone level (FT4) and subject characteristic as predictive factors observed at 3-, 6- and 12-month post- treatment were compared and analyzed. Among 46 patient involved in this study, 23 patients demonstrated remission of hyperthyroidism based on TRAb evaluation at 12-month. The size of thyroid at onset of disease in 30 (65%) patients was grade 2 or above (p<0.05). Free FT4 levels at the end of observation (12 month) was 1.9±0.6 ng/ dL in recurrent and 1.4±0.5 ng/dL in remission group (p<0.05). TRAb levels at early of study was higher in the recurrent group (p<0.05). Logistic regression analysis demonstrated that thyroid size, FT4 level, and TRAb at diagnosis were associated with recurrencies. In conclusion, GD patients with large thyroids size, high TRAb levels, and high FT4 level at the onset of disease tended to fail to respond to ATD and were associated with recurrence incidence.

COMPUTED TOMOGRAPHY FOR DIAGNOSING GRAVES OPHTALMOPATHY

Graves ophtalmopathy (GO), thyroid eye disease (TED) and thyroid - associated orbitopathy (TAO) are terms referring to an autoimmune inflammatory process that affects the adipogenesis of orbital fat and periorbital tissue, associated with dysthyroidism. On imaging, such as computed tomography (CT) thyroid -associated orbitopathy (or thyroid -associated ophtalmopathy) is characterised by symmetrical and bilateral proptosis, secondary to extra-ocular muscle (EOM) enlargement and expansion of orbital fat. Imaging studies ca be useful in identifying patients risk to develop dysthyroid optic neuropathy and initiating early treatment of the condition, avoiding permanent visual loss. The purpose of this study was to reveal the prevalence of thyroid ophtalmopathy imaging considerations in Graves disease patients. A total of 19 patients were evaluated on computed tomography scanning the diameters and density of extra-ocular muscles, muscular index, proptosis, width of the optic nerve, width of superior ophthalmic vein and lacrimal gland position.

Identification of Novel Environmental Substances Relevant to Pediatric Graves' Disease.

Graves’ disease (GD) is the most common cause of hyperthyroidism, yet a relatively rare disease in the pediatric population. GD is a complex disorder influenced by both genetic and environmental factors. In this study, we aimed to find new environmental factors influencing the pathogenesis of GD. We investigated serum substances in 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We measured total iodine by inductively coupled plasma-mass spectrometry (ICP-MS), analyzed perfluorinated compounds via ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS), and explored other environmental substances using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) analysis. Twenty-nine single-nucleotide polymorphisms (SNPs) in eight genes related to GD were analyzed by SNaPshot. The serum total iodine was significantly higher in GD group, but its association with GD onset was weak, only with Exp(B) value near 1. The perfluorinated compound levels were not different between the two groups. More importantly, we found 16 environmental substances significantly different between GD and control groups, among which ponasterone A is a risk factor (p = 0.007 and Exp(B) = 14.14), while confertifoline is a protective factor against GD onset (p = 0.002 and Exp(B) = 0.001). We also identified 10 substances correlated significantly with thyroid indices in GD patients, among which seven associated with levels of the thyroid autoantibody TPOAb. No known SNPs were found predisposing GD. In this study, we explored a broad variety of environmental substances and identified novel factors that are potentially involved in the pediatric GD pathogenesis.

IgG4 as a Biomarker in Graves' Orbitopathy.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory disorder associated with fibrosis and abundant tissue lymphoplasmacytic infiltrations. It typically affects the pancreas, the salivary glands, and the retroperitoneal space. However, it might also involve multiple other organs, including the orbit and the thyroid. Recent studies have suggested that IgG4 plays a role in the pathophysiology of autoimmune thyroid diseases. This ultimately led to the establishment of new clinical entities called IgG4-related thyroid disease and thyroid disease with an elevation of IgG4. The aim of this paper is to describe the pathophysiological, histopathological, and clinical features of Graves' Disease (GD) and Graves' Orbitopathy (GO) with elevated IgG4 levels. Multiple studies have demonstrated higher IgG4 serum concentrations in GD patients than in healthy euthyroid controls. Depending on the studied population, elevated serum IgG4 levels occur in 6.4-23% (average: 10.3%) of all patients with GD, 8.3-37.5% (average: 17.6%) of patients with GO, and 0-9.8% (average: 5.4%) of patients with GD without GO, while GO patients comprise 37.5-100% (average: 65.8%) of all GD patients with elevated IgG4 levels. Characteristic features of GD with elevated IgG4 levels include lower echogenicity of the thyroid gland on ultrasound examination, peripheral blood eosinophilia, higher prevalence of orbitopathy, and better response to antithyroid drugs with a tendency to develop hypothyroidism when compared to patients with GD and normal levels of IgG4. Typical signs of GO accompanied by increased concentration of IgG4 include younger age at diagnosis, and more severe course of the disease with a higher Clinical Activity Score (CAS).. We strongly recommend considering the diagnosis of GO with elevated IgG4 in patients with an established diagnosis of GD, elevated serum IgG4 levels, and clinical features of ophthalmic disease overlapping with those of IgG4-related orbital disease.

Precision Medicine in Graves' Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody.

BackgroundCD40, a key co-stimulatory molecule expressed on antigen-presenting cells, is genetically associated with a number of autoimmune diseases including Graves’ disease (GD). Therefore, recent therapies targeting CD40 have been developed, including the anti-CD40 monoclonal antibody Iscalimab. In a recent pilot study, Iscalimab was shown to induce clinical remission in ~ 50% of GD patients, but the reason why only 50% of GD patients responded is not known. The aim of our study was to test the hypothesis that specific CD40 single nucleotide polymorphism (SNP) genotypes and haplotypes are associated with clinical response of GD patients to Iscalimab.MethodsWe extracted genomic DNA from the whole blood of 13 GD patients treated with Iscalimab, and genotyped seven CD40 single nucleotide polymorphisms (SNPs) associated with autoimmunity. Additionally, we analyzed CD40 mRNA expression levels in whole blood. The patients’ CD40 SNP genotypes and mRNA levels were tested for association with clinical response to Iscalimab.ResultsThree common haplotypes, designated haplotypes A, B, and C, were identified. Haplotypes B and C were associated with higher CD40 mRNA levels and clinical response to Iscalimab (i.e., patients achieving euthyroidism without need for additional medications), while haplotype A was associated with decreased CD40 mRNA levels and no response to Iscalimab.ConclusionOur data suggest that genetic polymorphisms in the CD40 gene drive its expression levels and response to Iscalimab. Polymorphisms associated with higher CD40 levels are also associated with clinical response to CD40-targeted therapies. These results set the stage to implementing precision medicine in the therapeutic approach to GD.

Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves' Disease and Hashimoto's Thyroiditis in Korean Patients.

BackgroundProgrammed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT).MethodsA total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome.ResultsGenotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0±25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment anti-TPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group.ConclusionThe genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

Abstract #996726: Clinical Efficacy of Thyroid-stimulating Immunoglobulin Detection for Diagnosing Graves’ Disease and Predictors of Responsiveness to Methimazole

As thyroid-stimulating immunoglobulins (TSI) are a sign of Graves' disease (GD), measuring TSI titers is becoming increasingly important for GD diagnosis. Only a few studies have assessed the efficacy of TSI detection for diagnosing GD in a Chinese population. This study evaluated the diagnostic accuracy of a new fully automated TSI immunoassay (ImmuliteTM TSI assay) in GD patients and compared it to a thyroid-stimulating hormone receptor antibody (TRAb) immunoassay (ELiATM TRAb assay). Additionally, clinical characteristics associated with responsiveness to methimazole in patients with newly diagnosed GD were preliminarily explored.

The VDR gene confers a genetic predisposition to Graves' disease and Graves' ophthalmopathy in the Southwest Chinese Han population.

Graves' disease (GD) is a common autoimmune disease manifesting with diffuse symmetric thyroid gland enlargement, pretibial myxedema, and Graves' ophthalmopathy (GO). Recently, the vitamin D receptor (VDR) gene has been linked to various autoimmune diseases. This study aimed to investigate the association of VDR gene polymorphisms with susceptibility to GD and GO in the Southwest Chinese Han population. A two-stage association study was performed in 1,209 controls and 650 GD patients by PCR-RFLP assay. Real-time PCR and ELISA were carried out to quantify gene expression and cytokine production. The first-stage study showed that the frequency of VDR/Apa I AA genotype was significantly increased in GD (Pc=1.67×10-2, OR=1.98). The second-stage and combined studies confirmed the association of VDR/Apa I with GD (AA genotype: Pc=3.45×10-4, OR=1.87; A allele: Pc=2.62×10-2, OR=1.20). The stratification analysis showed that GO patients had a higher frequency of the VDR/Apa I AA genotype (Pc=8.69×10-5, OR=2.84). Functional experiments showed a decreased VDR expression and TGF-β1 production as well as an increased IL-17 production in VDR/Apa I AA genotype carriers. The VDR/Apa I polymorphism is significantly associated with GD and GO, and it may be involved in the development of GD and GO by influencing VDR mRNA expression levels and the secretion levels of cytokines.

Long-term outcomes of Graves’ disease in children and adolescents receiving antithyroid drugs

PurposeAntithyroid drugs (ATDs) are primarily used as an initial treatment in pediatric patients with Graves’ disease (GD). We aimed to investigate the long-term outcomes in pediatric GD patients receiving ATDs.MethodsRetrospective data from a single center were collected from April 2003 to July 2020. A total of 98 children and adolescents aged 2–16 years diagnosed with GD and receiving ATDs was enrolled. We investigated the factors correlated with remission by comparing children who achieved remission after 5 years and those with persistent disease.ResultsThe study included 76 girls (77.6%) and 22 boys (22.4%). During the 5-year follow-up period, 18 children (18.3%) maintained remission, ATDs could not be discontinued in 74 patients (75.5%), and relapse occurred in 6 patients (6.2%). The remission group had significantly lower thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII) level at diagnosis (P=0.002) and 3 months (P=0.002), 1 year (P=0.002), 2 years (P≤0.001), 3 years (P≤0.001), 4 years (P≤0.001), and 5 years (P≤0.001) after ATD treatment than did the nonremission group. The remission group also had a shorter time for TBII normalization after ATD treatment (P≤0.001). Multiple logistic regression analysis showed that the time to TBII normalization (cutoff time=2.35 years) was related to GD remission (odds ratio, 0.596; 95% confidence interval, 0.374–0.951).ConclusionsTBII level and time to TBII normalization after ATD treatment can be used to predict remission in pediatric GD patients.

Evaluating the role of circulating dendritic cells in methimazole-treated pediatric Graves’ disease patients

Evaluating the role of circulating dendritic cells in methimazole-treated pediatric Graves’ disease patients

Evaluating the role of circulating dendritic cells in methimazole-treated pediatric Graves’ disease patients

Evaluating the role of circulating dendritic cells in methimazole-treated pediatric Graves’ disease patients

Evaluating the role of circulating dendritic cells in methimazole-treated pediatric Graves’ disease patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)