Concurrence of myasthenia gravis and thyroid disorders: A retrospective database study / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;"><strong>INTRODUCTION</strong><strong>:</strong> Both myasthenia gravis (MG) and autoimmune thyroid diseases (AITDs) are autoimmune diseases. Graves'disease (GD) is the most common AITD reported to be associated with MG. Currently, there is limited data on prevalence and clinical features/outcomes of MG in various thyroid diseases in a large database report.</p><p style="text-align: justify;"><strong>METHODOLOGY:</strong> A total of 872 patients with MG and 97,251 patients with thyroid disorders had been recorded by the tertiary hospital database. The study period was between 1997 and 2017. Patients with a thyroid disorder and MG were identified by the ICD-10-CM code. Clinical courses of MG accompanied by thyroid disorders were studied.</p><p style="text-align: justify;"><strong>RESULTS:</strong> During the 20-year study period, there were 872 patients with MG and 97,251 patients with thyroid disorders. In the group with thyroid disorders, 28,886 patients (29.70%) had GD, 1,612 patients (1.66%) had Hashimoto's thyroiditis, 13,172 patients (13.54%) had toxic goiter and 53,581 patients (55.10%) had nontoxic goiter. 97 patients had been diagnosed with both MG and thyroid disorders. Among the four types of thyroid disorders, the rate of MG was highest in HT group (9.92/1,000 HT patients). There were four significant factors among four groups of thyroid disorders including age of onset of thyroid disease (p 0.004), MG classification (ppp 0.034). Among the four groups of thyroid disorders, patients with MG and HT were diagnosed with thyroid disease at the youngest age (27 years) compared with other thyroid diseases. Additionally, the MG patients with HT also had the highest proportion of MG class 4-5 a/b (7 patients, 43.75%), received prednisolone treatment (15 patients, 93.75%), received immunosuppressants (9 patients, 56.25%), received IVIG or PLEX (5 patients, 31.30%), and had thymoma (6 patients, 46.15%).</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> MG is most prevalent in patients with HT. Patients with both MG and HT had more severe MG status and had higher rate of thymoma.</p>

Association between C1q gene polymorphisms and autoimmune thyroid diseases

ABSTRACT Objective In the present study, we aimed to assess the associations of C1q gene polymorphisms with autoimmune thyroid diseases (AITD) susceptibility. Subjects and methods A set of 1,003 AITD patients (661 with Graves' disease and 342 with Hashimoto's thyroiditis) and 880 ethnically- and geographically-matched controls from Chinese Han population were included. Five common single nucleotide polymorphisms (SNPs) (rs294185, rs292001, rs682658, rs665691 and rs294179) in C1q gene locus were genotyped. Frequencies of genotypes and alleles were compared between patients and controls, and haplotype analysis was also performed. Results There was no statistically significant difference between AITD patients and controls in the frequencies of alleles of rs294185 (P = 0.41), rs292001 (P = 0.71), rs682658 (P = 0.68), rs665691 (P = 0.68) and rs294179 (P = 0.69). There was also no statistically significant difference between AITD patients and controls in the frequencies of genotypes of rs294185 (P = 0.72), rs292001 (P = 0.89), rs682658 (P = 0.83), rs665691 (P = 0.90) and rs294179 (P = 0.43). Stratified analyses showed that none of those five SNPs in C1q gene were associated with Graves' disease or Hashimoto's thyroiditis (all P values > 0.05). Haplotype analysis revealed that there were no obvious genetic associations of C1q gene polymorphisms with AITD susceptibility. Conclusions We, for the first time, identified the associations between C1q gene SNPs and AITD, and our findings suggested that five common SNPs in C1q gene were not associated with AITD susceptibility in Chinese Han population.

Research progress on thyroglobulin and its antibody / 医学研究生学报

Tg gene polymorphism, HLA and iodine interaction with Tg may be involved in the pathogenesis of autoimmune thyroid disease.Moreover, thyroglobulin antibody (TgAb), an important symbol of autoimmune thyroid disease, is also closely related to the development of autoimmune thyroid disease.In addition, the differences of TgAb IgG isoforms expression level also have broad application prospects in the classification and diagnosis of autoimmune thyroid disease.By researching on Tg, we review the pathogenesis of autoimmune thyroid disease and provided the evidence for its diagnosis and clinical treatment.

Meta Analysis of Relationship between Helicobacter pylori Infection and Autoimmune Thyroid Diseases / 中国医科大学学报

Objective To investigate the association between Helicobacter pylori(H. pylori) infection and Autoimmune thyroid diseases (ATDs). Methods The literatures on the association of H. pylori with ATDs were retrieved by searching databases from the inception of each da?tabase to October 2015. Data extraction and quality assessment were completed by two authors. Meta analysis was performed using RevMan 5.3 software,calculating the odds ratio and 95%confidence interval. Results Twelve papers were included for the meta?analysis. The total sample size was 1 615,with 918 cases and 697 controls,respectively. Compared with the controls,H.pyloriinfection significantly increased the risk of auto?immune thyroid diseases development with a pooled of[OR=1.86,95%CI(1.18,2.94)]. H.Pylori?CagA infection significantly increased the risk of autoimmune thyroid diseases development with a pooled of[OR=2.66,95%CI(1.61,4.41)]. H. pylori infection is associated with Graves dis?ease[OR=3.37,95%CI(1.90?5.97)]and Hashimoto′s thyroiditis[OR=1.83,95%CI(1.22,2.76)]. The results of publication bias and sensitivi?ty analysis confirmed the reliability and stability of this meta analysis. Conclusion H. pylori infection may be associated with an increased risk of developing the autoimmune thyroid diseases.

Change of serum 25-(OH)D3 levels in patients with different subtypes of autoimmune thyroid diseases / 中国综合临床

Objective To investigate the relationship between serum 25-(OH) D3 and autoimmune thyroid diseases (AITD).Methods Serum levels of 25-(OH) D3, thyroid antibodies (thyroid stimulating hormone receptor antibody (TRAb), TGAb (thyroid globulin antibody), thyroid peroxidase antibody (TPOAb) and thyroid function of 32 cases patients with Graves' diseases (GD), 17 cases patients without remission of GD,10 cases patients with remission of GD,35 cases patients with Hashimoto's thyroiditis (HT),and 58 cases healthy subjects were measured,and the relationships between serum 25-(OH) D3 and the above clinical index were analyzed.Results The serum level of 25-(OH) D3 in patients with GD or HT were obviously lower than that in healthy subjects((50.75±17.60) μg/L, (36.40±21.65) μg/L, (43.05±19.53) μg/L,P＜0.05).No significant difference of the serum level of 25-(OH) D3 was found between patients refractory of GD and those with GD in remission((32.43±17.50) μg/L, (31.88±14.48) μg/L,P=0.866).However,compared with the normal control group,both diseased groups showed significantly decrease (P＜0.05).No correlation was found between serum 25-(OH) D3 and TRAb, FT3, Fr4 as well as TSH in GD group.No correlation was found between serum 25-(OH) D3 and TGAb, TPOAb (P＞ 0.05).Conclusion Serum vitamin D levels are decreased in patients with AITD, which has been speculated as a potential therapeutic method for AITD, though further investigations are needed to establish the precise role of 25-(OH) D3 in AITD.

Effects of Iodine excess,polyinosinic-polycytidylic acid and thyroglobulin induced thyroiditis in mice on Toll-like receptor 3 expression / 中国地方病学杂志

Objective To observe the effect of iodine excess(HI),polyinosinic-polycytidylic acid[Poly(I:C),Poly]and thyroglobulin(TG)on the thyroid of mice by the expression of Toll-like receptor 3(TLR3)to reveal the functional role of TLR3 in autoimmune thyroiditis.Methods Forty-two non-obese diabetic mice,body weight (20±3)g,were divided into six groups:control group,HI group,Poly group,TG group,HI+TG group,HI+Poly group. Fed with deionized water and injected intraperitoneally with physiological saline 0.1 ml each day for a week, the mice in control group were injected with physiological saline every other day at the same dose for 1 week before they were sacrificed; HI group drank 0.05% NaI water and were injected intraperitoneally with physiological saline same as control group; Poly group drank deionized water and were injected intraperitoneally with poly 0.1 ml (1 g/L)each day of the week, then the mice were injected with Poly every other day at the same dose for 1 week before they were sacrificed; TG group drank deionized water and were injected intraperitoneally with physiological saline same as control group, immunized with 0.1 mg TG by subcutaneously injecting and the immunization was enhanced after they were fed half dose for 4 and 8 weeks separately. In HI + Poly group, the treatment was the same as HI group and Poly group; HI + TG group: the treatment was the same as HI group and TG group. Eight weeks later, mice were sacrificed and thyroids were taken to make frozen sections, Hematoxylin-Eosin (HE) staining was employed to observe the morphological change of the thyroids. The expression of TLR3 of thyroids was observed under fluorescence microscope after Immumofluorescence using TLR3 antibody and TR3-positive cells were analyzed in the thyroid density. Results HE staining showed thyroids of Poly group had no inflammation under microscope.There were different degrees of inflammatory cell infiltration in HI group and TG group. The inflammatory cell infiltration and the damage of follicular thyroid of HI + TG group and HI + Poly group were serious, and the degrees of inflammation were higher over "++". Thyroid follicular epithelial cell with TLR3 expression could be seen in Poly group and HI group, meanwhile, there were TLR3 strong positive inflammatory cells in HI group under fluorescent microscope. Using stereological analysis of TLR3-positive cell density in the thyroid, the difference between groups was statistically significant(F=7.870, P<0.01 ). TLR3-positive cell density in the thyroid of HI + Poly group was higher[ (9.287 ± 0.522)mm2] than control group[ (0.062 ± 0.025)mm2, P < 0.01] significantly, meanwhile, the density in HI + Poly group was higher than HI group [ (2.574 ± 0.257 )mm2] and Poly group[ (1.361 ± 0.148 )mm2, all P < 0.01]. The density in HI + TG group[ (4.843±0.405)mm2] was higher than HI group and TG group[(1.601 ±0.268)mm2, all P < 0.01 )]. Conclusions Excessive iodine and thyroglobulin can induce thyroiditis, and stimulate the expression of TLR3 in the thyroid follicular epithelial, Poly aggravated thyroiditis induced by iodine excess in NOD mice; TLR3 positive inflammatory cells also appeared in inflammatory region, suggesting that TLR3 is involved in the pathogenesis of autoimmune thyroiditis

Advances in the genetic pathogenesis of autoimmune thyroid diseases / 中华内分泌代谢杂志

Autoimmune disease is the result of interplay between genetic and environmental factors, Immunoregulatory genes and thyroid specific genes play important roles in the pathogenesis of autoimmune thyroid diseases.

Association of FcRL3 gene polymorphism with autoimmune thyroid diseases / 中华内分泌代谢杂志

The polymorphism in the exon 4 of FcRL3 gene was evaluated by PCR-FPLR in 506 patients with Graves' disease (GD), 80 with Hashimoto thyroiditis (HT) and 261 normal subjects in Chongqing. The data suggest that 82G allele in exon 4 of FcRL3 gene may be susceptible to GD in male patients of Chongqing Hart nationality.

Relationship between the Th1/Th2 Cytokines Imbalance and Autoimmune Thyroid Diseases / 中国医师杂志

Objective To analyze the relationship between serum Th1/Th2 cytokines levels and autoantibodies against thyroid, and explore the role of Th1/Th2 cellular immunity imbalance in the pathogenesis of autoimmune thyroid diseases(AITD). Methods 21 patients with Graves'desease(GD), 18 cases with Hashimoto's thyroiditis(HT), 17 cases with non-toxic nodular goiter(NTNG) and 20 healthy subjects were enrolled in this study. The serum concentrations of their Th1 cytokines (IFN-?,IL-2) and Th2 cytokines (IL-4,IL-10) were assayed by ELISA. The serum levels of their thyrotropin receptor antibodies(TRAb), thyroglobulin antibodies (TGAb) and thyroid peroxidase antibodies(TPOAb) were measured by routine methods. The relationship between the serum Th1, Th2 cytokines levels and serum TRAb, TGAb, TPOAb levels were analyzed. Results The serum levels of IL-4 and IL-10 in patients with GD were significantly higher than those in patients with HT,NTNG and healthy subjects(P

Measurement of Anti-GAD65 Autoantibodies in Patients with Type 1 Diabetes Mellitus with / without Autoimmune Thyroid Diseases (Immunoblotting followed by Immunoprecipitation) / 대한내분비학회지

BACKGROUND: Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The broad concept of polyendocrinopathies takes into consideration that patients affected by at least one endocrine disease may have another autoimmune disorder or express specific autoantibodies. Anti-glutamic acid decarboxylase autoantibodies, now recognized as one of the major serological markers for type 1 diabetes has been reported to be higher in type 1 diabetes patients with autoimmune thyroid diseases (ATD) than in those without ATD. The objective of the present study was to evaluate the prevalences of GAD65 antibodies applying a newly developed assay(anti-GAD65) in type 1 diabetes patients with and without ATD. METHODS: We developed a new anti-GAD65 assay after mammalian expression of a recombinant GAD65 antigen. Since the detection of anti-GAD65 is rather complicated and insensitive due to inherent antigenic difference of antibody recognition in conventional assays, we applied this new approach in measuring anti-GAD autoantibodies and compared the result with ICA and anti-GAD measurement using the purified porcine GAD (anti-GAD) in 109 cases of type 1 diabetes, 29 of whom had concomitant ATD (mean age at diagnosis: 7.9 yr, mean duration of type 1 diabetes: 4.5 yrs). RESULTS: The overall prevalence of anti-GAD65 antibodies was 65% (71 of 109) in patients with Korean type 1 diabetes. Prevalences and titers of anti-GAD65 had not changed much after controlling for the duration and the status of concomitant ATD. In contrast, the prevalence of anti-GAD was 56%(61 of 109), while that of ICA(+) WAS 36% in type 1 diabetes patients. We found significant, but not strong association of anti-GAD65 either with anti-GAD(r=0.4, p<0.01) or with ICA(r=0.6, p< 0.001). CONCLUSION: From this, we could assess that autoantibodies are present at comparable sensitivity and specificity in Korean type 1 diabetes patients. This anti-GAD65 assay, another immunologic marker for type 1 diabetes might also confer disease susceptibility among Koreans, but no increase in the prevalence or in the titer in patients with ATD may suggest that this marker is unlikely to give much benefit, for the detection of the overlapping disease of type 1 diabetes and ATD.

The association of cytotoxic T lymphocyte-associated antigen 4 gene polymorphism with type 1 diabetes mellitus and autoimmune thyroid diseases in Chinese Han population / 中华内分泌代谢杂志

Objective To investigate the association of cytotoxic T lymphocyte associated antigen 4 (CTLA 4) gene polymorphism with type 1diabetesmellitusandautoimmunethyroiddiseases. Methods The A/G phenotype at position 49 of the CTLA 4 gene exon 1 was determined by PCR RFLP method in 33 classic type 1 diabetes patients, 57 latent autoimmune diabetes in adults (LADA) patients, 122 autoimmune thyroid disease patients and 84 healthy control subjects of Chinese Han. Results The frequency of the CTLA 4 G phenotype was significantly higherintype1diabetespatientsthanthatincontrol subjects (55.6% vs 36.9%, P=0.0005). Neither the presence nor the absence of G allele influenced the occurrence of islet autoantibody (ICA) and glutamate decarboxylase antibody (GADA). The strong association of the CTLA 4 G allele with AITDs was showed in our study (66.4% vs 36.9%, P

Tumor necrosis factor-? gene polymorphism is related to thyroid-associated ophthalmopathy / 中华内分泌代谢杂志

The -1031T/C polymorphism of tumor necrosis factor-? (TNF-?) gene was determined by PCR-RFLP in 54 patients with thyroid-associated ophthalmorpathy (TAO), 60 patients with autoimmune thyroid disease (AITD) without ophthalmopathy and 76 healthy subjects. The results showed that the frequencies of TC+CC genotype and C allele in TAO group, especially in male patients, were significantly higher than those in the other two groups (both P