Graves' Disease Group Research Articles

Cancer Risks of Patients with Graves' Disease Who Received Antithyroid Drugs as Initial Treatment: A Nationwide Population-Based Analysis.

Background: Population-based studies that examine the associations between hyperthyroidism and cancer risk have yielded inconsistent results. It remains unclear whether the risks of different cancers increase in patients with Graves' disease (GD) who received antithyroid drugs (ATDs) as initial treatment. We aimed to determine whether cancer risk increases in patients with GD, compared with controls. Methods: This nationwide retrospective cohort study utilized data from the National Health Information Database of South Korea. We included 29,502 patients aged >20 years with GD, who received ATDs as initial treatment, and 57,173 age- and sex-matched controls. The primary outcome was the incidence of various types of cancers. Hazard ratios (HRs) with confidence intervals (CIs) for cancer risk were estimated using Cox proportional hazards models. We also analyzed HR by follow-up period since the diagnosis of GD, accounting for surveillance effect. Results: The risk of biliary tract and pancreatic cancers (HR: 1.41, CI: 1.24-1.60), thyroid cancer (HR: 15.51, CI: 12.29-19.57), prostate cancer (HR: 1.48, CI: 1.28-1.71), and ovarian cancer (HR: 1.31, CI: 1.13-1.52) was elevated in the GD group than in the control group even after the first year of follow-up was excluded. The increased risk of these cancers persisted after a follow-up period of more than 5 years. The risk of thyroid cancer in patients with GD was higher during the initial follow-up period (1 to <2 years) (HR: 19.35, CI: 7.66-48.87) compared with that in the follow-up period exceeding 2 years. The cancer risk estimates remained significant after excluding patients with GD who underwent subsequent radioactive iodine therapy. Conclusion: In this large-scale population-based study, GD was associated with increased risks of biliary tract and pancreatic, prostate, ovarian, and thyroid cancers. The increased risk of thyroid cancer, particularly during the initial follow-up period, may be a surveillance effect.

NrCAM activates the NF-κB signalling pathway by competitively binding to SUMO-1 and promotes Th17 cell differentiation in Graves' disease.

This study aimed to explore the molecular mechanism of neuronal cell adhesion molecule (NrCAM) by regulating Th17 cell differentiation in the pathogenesis of Graves' disease (GD). Naïve CD4+ T cells were isolated from peripheral blood mononuclear cells of GD patients and healthy control (HC) subjects. During the differentiation of CD4+ T cells into Th17 cells, NrCAM level in GD group was improved. Interference with NrCAM in CD4+ T cells of GD patients decreased the percentage of Th17 cells. NrCAM overexpression in CD4+ T cells of HC subjects increased the percentage of Th17 cells and upregulated p-IκBα, p50, p65, c-Rel protein expressions, and NF-κB inhibitor BAY11-7082 partially reversed NrCAM effect. NrCAM overexpression promoted the degradation of IκBα, and overexpression of small ubiquitin-related modifier 1 (SUMO-1) inhibited IκBα degradation. NrCAM overexpression reduced IκBα binding to SUMO-1. During Th17 cell differentiation in HC group, NrCAM overexpression increased IL-21 levels and secretion, and IL-21 neutralizing antibody reversed this effect. IL-21 level was decreased after p65 interference in CD4+ T cells of HC subjects. p65 interacts with IL-21 promoter region. In conclusion, NrCAM binds to SUMO-1 and increases phosphorylation of IκBα, leading to activation of NF-κB pathway, which promotes Th17 cell differentiation.

A meta-analysis: elucidating diagnostic thresholds of peak systolic flow velocities in thyroid arteries for the discrimination of Graves' disease and destructive thyrotoxicosis.

This meta-analysis examines peak systolic velocities (PSVs) in thyroid arteries as potential biomarkers for thyroid disorders, which includes treated and untreated Graves' disease(GD) and destructive thyrotoxicosis(DT). A search across databases including PubMed, Google Scholar, Embase, and Web of Science identified studies assessing peak systolic flow velocity in the inferior thyroid artery (ITA-PSV) and superior thyroid artery (STA-PSV) diagnostic efficacy in GD and DT.And the search was restricted to publications in the English language.The analysis compared STA-PSV and ITA-PSV across patient groups, evaluating intra-group variances and synthesizing sensitivity and specificity data. The analysis covered 18 studies with 1276 GD, 564 DT patients, and 544 controls. The difference of STA-PSV between GD group, DT group and normal group and the difference of ITA-PSV were analyzed in subgroups, and there was no statistical significance between subgroups when comparing any two groups. Normal subjects displayed intra-group ITA-PSV and STA-PSV differences with established cut-off values of 20.33 cm/s (95% CI, 17.48-23.18) for ITA-PSV and 25.61 cm/s (95% CI, 20.37-30.85) for STA-PSV. However, no significant intra-group differences were observed in the STA-PSV and ITA-PSV cut-off values among groups with GD or DT. The combined cut-off values for these patient groups and normal subjects were 68.63 cm/s (95% CI, 59.12-78.13), 32.08 cm/s (95% CI, 25.90-38.27), and 23.18 cm/s (95% CI, 20.09-26.28), respectively. The diagnostic odds ratio(DOR) for these values was 35.86 (95% CI, 18.21-70.60), and the area under the summary receiver operating characteristic (SROC) curve was 0.91, with a sensitivity estimate of 0.842 (95% CI, 0.772-0.866). PSVs in thyroid arteries are useful diagnostic tools in distinguishing DT from GD. A PSV above 68.63 cm/s significantly improves GD diagnosis with up to 91% efficacy. No notable differences were found between superior and inferior thyroid arteries in these conditions.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Examination of quality of life and psychiatric symptoms in childhood Graves' disease.

The aim of our study is to examine the emotional, behavioral problems, and psychiatric symptoms of children diagnosed with Graves' disease (GD), to assess their quality of life, and to compare with control group. The research was planned as a cross-sectional study and included 16 patients with GD (13 female and three male) and 29 healthy children for control group (19 female and 10 male). Sociodemographic form, Pediatric Quality of Life Inventory, Revised Child Anxiety and Depression Scale-Child Version (RCADS-CV), Strengths and Difficulties Questionnaire (SDQ), Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S), and Affective Reactivity Index scale were applied to the children and their families. Eighty one percent of GD group (GG) (n=13, mean age 15.1±2.2) and 66 % of control group (CG) (n=19, 14.6±2.2) were girls. No significant difference was found between GG and CG in terms of quality of life, anxiety, and depression scores. GG had higher scores in affective reactivity index, SDQ-P total score, and T-DSM-IV-S total scores (p values 0.039; 0.009; 0.023, respectively). While no significant difference was detected in the T-DSM-IV-S-inattention and hyperactivity scores, significantly higher scores were detected in oppositional defiance and conduct disorder scores (pvalues 0.172; 0.294; 0.019; 0.027, respectively). In children with GD, irritability, oppositional defiant, and conduct disorder symptoms have been detected. Children with these mental health symptoms experience behavioral and emotional difficulties in their daily lives. It is important to follow up children with GD for possible comorbid psychiatric disorders.

Interleukin (IL)-23, IL-31, and IL-33 Play a Role in the Course of Autoimmune Endocrine Diseases.

Interleukins (IL)-23, 31, and 33 are involved in the regulation of T helper 17 (Th17)/regulatory T (Treg) cells balance. The role of IL-23, 31 and 33 in non-endocrine autoimmune diseases has been confirmed. Data on the involvement of these cytokines in endocrine autoimmune diseases are limited. This study aimed to determine the involvement of cytokines regulating the T helper 17 (Th17)/regulatory T (Treg) cells axis in the course of autoimmune endocrine diseases. A total number of 80 participants were divided into 4 groups: the autoimmune polyendocrine syndrome (APS) group consisting of APS type 2 (APS-2) and type 3 (APS-3) subgroups, the Hashimoto's thyroiditis (HT) group, the Graves' disease (GD) group and the control (C) group. Fifteen cytokines related to Th17 and Treg lymphocytes were determined in the serum of all participants. Higher levels of IL-23 and IL-31 were found in the APS, GD, and HT groups compared to the C group. Higher levels of IL-23 and IL-31 were also observed in the APS-2 group, in contrast to the APS-3 group. Correlation analysis of variables in the groups showed a statistically significant correlation between the cytokines IL-23, IL-31, and IL-33 in the APS and APS-2 groups, but no correlation in the APS-3 and C groups. IL-23 and IL-31 are independent factors in the course of HT, GD, and APS-2, in contrast to APS-3. The positive correlation between IL-23 and IL-31, IL-23 and IL-33, and between IL-31 and IL-33 in the APS, APS-2 groups, but the lack of correlation in the APS-3 and C groups may further suggest the involvement of these cytokines in the course of Addison's disease.

Incidence of the postpartum diagnosis of thyroid eye disease in relation to thyroid function in Graves' disease.

It has been reported that Graves' disease (GD) sometimes improves spontaneously during pregnancy, although exacerbation of GD during postpartum period or relapse of hyperthyroidism caused by GD might occur. This study aimed to investigate the incidence of postpartum diagnosis of thyroid eye disease (TED) in relation to thyroid dysfunction. This retrospective cross-sectional study enrolled 11,104 deliveries from the patients with GD between January 2004 and August 2022. Within the 12-month postpartum period, 72 patients (0.65%) were diagnosed with TED. The thyroid function of the 72 patients comprised 9 remission, 13 continued antithyroid medicine, and 50 thyroid dysfunction; 30 newly diagnosed GD, 1 hypothyroidism, and 19 relapse/recurrence of GD. In the 49 patients with thyroid dysfunction, no difference was observed in the median values of thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and TSH receptor stimulating antibody between the TED diagnosis and the development of hyperthyroidism. However, when the patients were classified into the newly developed GD and relapse/recurrence of GD groups, the difference became significant and the TRAb level was high in the newly developed GD (16.1 vs. 5.0 IU/L, p < 0.0001, and 15.0 vs. 6.0 IU/L, p = 0.0003). Thyroid dysfunction preceded TED diagnosis in more than half of the patients and the median time for each event was 6.5 vs. 8.1 months. The active phase TED was observed in 8 of the 72 patients. Of the 72 patients newly diagnosed with TED in postpartum, two-thirds were accompanied by thyroid dysfunction and 8 of them were in active phase.

The Potential Role of Pyrroloquinoline Quinone to Regulate Thyroid Function and Gut Microbiota Composition of Graves' Disease in Mice.

Graves' disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD's intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

SAT548 Incidental Papillary Thyroid Carcinoma Diagnosed After Total Thyroidectomy For Recurrent Grave's Disease

Abstract Disclosure: S.U. Perez-Martinez: None. S. Bao: None. Introduction: Whether Graves’ disease (GD) increases the risk of thyroid cancer (TC) has been a long-time topic of debate. Some studies reported increased risk of TC in GD, particularly when patients with GD have thyroid nodules. Other studies suggested the prevalence of incidental differentiated TC in GD is comparable to euthyroid goiter. Here we present a case of a 39-year-old female with a thyroid nodule and recurrent GD who underwent total thyroidectomy (TT) and was found to have a 0.4cm incidental papillary TC. Clinical case: 39 year-old female patient was diagnosed with hyperthyroidism due to GD and a 1.26x2.04x2.88cm complex right thyroid nodule at age 28, based on laboratory and thyroid ultrasound (US) studies, respectively. Fine needle aspiration showed a follicular lesion favoring colloid nodule. Patient preferred conservative measures at that time. She was treated with methimazole for 3 years and went into remission. Her thyroid nodule was monitored with serial thyroid US (every 1-2 years) for 7 years and remained stable. However, 7 years after discontinuation of methimazole, she developed recurrent hyperthyroidism, with laboratory findings of suppressed TSH of &amp;lt;0.04 (normal 0.35-5.5 mcu/mL), elevated free T4 of 2.4 (normal 0.8-1.8 ng/dL) and Thyroid Stimulating Immunoglobulin of 8.01 (normal &amp;lt; 0.054 IU/L). Patient was restarted on Methimazole 10mg daily. Her TSH remained to be low at &amp;lt; 0.015 (normal 0.35-3.6 mcu/mL) 4 months later, at which point more definitive treatment options including radioactive iodine ablation or TT were again discussed, and the patient opted to undergo TT, which was performed successfully 2 months later. Surgical pathology was consistent with GD, an encapsulated, fibrotic, and calcified nodule consistent with infarcted follicular lesion but also a 0.4cm incidental Papillary TC in right thyroid lobe. Surgical margin was clean, no extrathyroidal extension, one perithyroidal lymph node was negative for malignancy. Patient has been doing well afterwards. Discussion: The prevalence and clinical significance of incidental differentiated TC in patients with GD have been controversial topics. Incidence of TC in GD was mostly reported to be 7-17%, but may be as high as 42%, based on thyroidectomy studies. However, a recent retrospective multicenter study suggested the concomitant TC in GD was considerably lower. No difference in TC aggressiveness, US findings, or prognosis were observed between nodular GD and non-nodular GD groups. The clinical outcomes of TC were also excellent. A Cleveland Clinic study suggested nodule size &amp;gt; 1cm predicted incidental TC whereas Thyroid Stimulating Immunoglobulin titers and disease duration did not. These data argue for screening patients with GD more aggressively for TC or treating GD patients with coexisting thyroid nodule more aggressively; as in our case, even if incidental TC was found, prognosis is favorable. Presentation Date: Saturday, June 17, 2023

Comprehensive analysis of chemokine gene polymorphisms in Korean children with autoimmune thyroid disease

Chemokines are chemotactic cytokines that can cause directed migration of leukocytes. The aim of this study was to examine differences in single nucleotide polymorphisms (SNP) of chemokine in AITD patients compared to normal controls. A total of 86 Korean pediatric patients were included in the patient group and 183 adults were included in the normal control group. To compare influences of several chemokine gene polymorphisms, 25 SNPs in 16 chemokine genes were analyzed. Genotype frequencies of CCL11(rs3744508)AA(OR = 6.9) and CCR2(rs1799864)AA(OR = 3.8) were higher in the AITD patients than in the controls, whereas CCL17(rs223828)CC was lower in the AITD patients than in the controls(OR = 0.4). In comparison between Graves' disease (GD) patients and controls, genotype frequency of CCL17(rs223828)CC(OR = 0.4) was lower in the GD group, whereas those of CCR2(rs1799864)AA(OR = 4.8) were higher in the GD group. The genotype frequency of CCL11(rs3744508)AA(OR = 11.3) was higher in Hashimoto's thyroiditis (HT) patients, whereas that of CXCL8(rs2227306)CC(OR = 0.4) was lower in HT patients. Polymorphisms of CCL11(rs3744508), CCL17(rs223828), and CCR2(rs1799864) might be associated with AITD, with CCL17(rs223828), CCR2(rs1799864) and CXCR2(rs2230054, rs1126579) affecting GD and CCL11(rs3744508) and CXCL8(rs2227306) affecting HT in Korean children.

Association Between NEAT1 rs512715 Gene polymorphism and Hashimoto Thyroiditis and Graves’ Disease: A Case-Control Study

Background: Some evidence demonstrated the relationship between long non-coding RNA and autoimmune disease development. The current study assessed the possible association between the nuclear enriched abundant transcript 1 (NEAT1) gene rs512715 polymorphism and Hashimoto and Graves’ diseases. Methods: Two hundred forty-eight participants with autoimmune thyroid disease (133 Hashimoto thyroiditis (HT) patients and 115 Graves’ disease (GD) patients) and 135 age- and sex-matched controls were enrolled in the study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping NEAT1 rs512715 polymorphism. Results: Significant differences were observed in the frequency of the CC genotype of rs512715 in the HT group compared to the controls; the CC genotype may act as a risk factor for HT development. Also, the dominant and recessive genetic models showed the same results. Regarding the frequency of alleles, the C allele frequency was higher in the HT group than in the controls. In the GD group, there was no significant difference in the distribution of genotypes and the genetic models. Also, no significant difference was observed in the frequencies of alleles in Graves’ patients. Conclusions: Our findings indicated that NEAT1 rs512715polymorphism might play an influential role in Hashimoto’s disease development as the risk factor.

Correlation between gut microbiota and the development of Graves’ disease: A prospective study

The association between gut microbiota and development of Graves' disease (GD) remains unclear. This study aimed to profile the gut microbiota of 65 patients newly diagnosed with GD before and after treatment and 33 physical examination personnel via 16S rRNA sequencing. Significant differences in the gut microbiota composition were observed between the two groups, showing relative bacterial abundances of 1 class, 1 order, 5 families, and 14 genera. After treatment, the abundance of the significantly enriched biota in the GD group decreased considerably, whereas that of the previously decreased biota increased considerably. Further, interleukin-17 levels decreased significantly. The random forest method was used to identify 12 genera that can distinguish patients with GD from healthy controls. Our study revealed that the gut microbiota of patients with GD exhibit unique characteristics compared with that of healthy individuals, which may be related to an imbalance in the immune system and gut microbiota.

The serum concentration and activity of DPP4 is positively related with the severity of hyperthyroidism in patients with Graves’ disease

Objective Graves’ disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune tolerance. Dipeptidyl peptidase-4 (DPP-4) is expressed on multiple immune cells. This study aimed to investigate the relationship between serum concentration/activity of DPP4 and the severity of hyperthyroidism in GD patients. Methods A total of 82 newly diagnosed drug-naive patients with GD hyperthyroidism, 20 patients with non-autoimmune thyrotoxicosis and 122 age- and sex- matched healthy controls were enrolled. The clinical parameters and serum concentration and activity of DPP4 were measured. Results The GD group had increased serum concentration and activity of DPP4 than the healthy controls and patients with non-autoimmune thyrotoxicosis, while no significant difference was observed in the latter two groups. Multivariate linear regression indicated that the serum concentration/activity of DPP4 were positively associated with FT3, FT4 and TRAb levels in the GD patients. And the positive association between serum concentration/activity of DPP4 and TRAb was remained even after adjustment for confounding factors (all p < 0.05). Conclusions The GD patients had significantly increased serum concentration/activity of DPP4. And the serum concentration/activity of DPP4 was positively associated with the severity of hyperthyroidism in GD patients. Key messages The activity and concentration of DPP4 in patients with Graves’ disease were higher than those in healthy controls. There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves’ disease. In patients with Graves ‘disease, serum DPP4 activity was positively correlated with TRAb levels.

Vitamin D Level Among Patients with Different Thyroid Diseases

To investigate the differences in vitamin D levels in patients with different types of thyroid disease and to investigate the factors influencing vitamin D levels in patients with thyroid disease, this study collected clinical data from 1603 patients with thyroid disease attending the Department of Endocrinology and Metabolism of the First People's Hospital of Yunnan Province and conducted a retrospective cross-sectional study. The clinical data of 1603 patients with thyroid diseases including Graves' disease (GD), subacute thyroiditis (SAT), autoimmune thyroid disease (AITD) and hypothyroidism (HP) were collected from the Department of Endocrinology and Metabolism of yunnan First People's Hospital. Gender, age, BMI, blood lipids, thyroid hormones, thyroid autoantibodies, and serum 25-hydroxyvitamin D(25(OH)D) levels were measured. Results: (1) The level of 25(OH)D in patients with different thyroid diseases was from high to low, in the following order: GD group (29.54±7.54 ng/ml), SAT group (28.01±7.14 ng/ml), AITD group (26.97±6.58 ng/ml), HP group (25.88±6.75 ng/ml), the differences were statistically significant (P<0.05). The 25(OH)D level in GD group was significantly higher than that in other groups (P<0.05), while the 25(OH)D level in HP group was significantly lower than that in SAT group (P<0.05). (2) The changing trend of thyroid hormone levels (T3, FT3 and FT4) was consistent with that of 25(OH)D (P <0.005). (3) 25(OH)D was established as the dependent variable with multiple linear regression equation, Y = 3.80 gender + 0.058FT3-0.036 age + 28.122(female as control group). Conclusions: There were significant differences in vitamin D levels among patients with thyroid diseases, with the highest vitamin D level in GD patients and the lowest vitamin D level in HP patients. The higher the thyroid hormone level, the higher the 25(OH)D, which may be related to the strength of the immune response or the effect of thyroid hormone on vitamin D synthase. Male and high levels of FT3 were associated with increased 25(OH)D levels in thyroid patients.

Measurement of Some Immunological Parameters, Hematologic Outcomes and Physiological Features for Graves' Disease in Babylon City, Iraq

Graves' disease (GD) is an autoimmune disease that infected some people and describe as a disorder in the thyroid gland that leads to a hyperactive thyroid gland leading to the overproduction of thyroid hormones resulting from an attached immune system for the thyroid gland The aims of this study were to Measurement of some immunological parameters (IL-2 &amp; IgG), hematologic outcomes (routine CBC tests), and physiological features of Graves' disease in Babylon City, Iraq. Study subjects (GD and Control Groups) &amp; Demographic data: Study conducted from January 2022 to March 2022, samples for immunologic (IL-2, IgG &amp; hematologic tests (routine CBC) were blood samples taken from both (n=94) Hospital-admitted patients with Graves' disease symptoms from Imam Al-Sadiq Teaching Hospital\ Thyroid gland diseases Center- First Floor and compare them with (60) represent healthy control, in both sexes, of different age groups ranging from (&gt;38-&lt;52 years)., in Babylon city. The researchers follow the Ethics committee of health &amp; academic directorates. Data analysis using SPSS system to determine significant differences between data, p-value less than (&lt;0.05) ANOVA. All values are expressed as the mean standard deviation (SD) for sex, age groups, and test results in both GD &amp; control groups.

Short- and long-term outcomes of patients with hyper or hypothyroidism following COVID vaccine.

Since the beginning of the wide-scale anti-Coronavirus disease 2019 (COVID-19) vaccination program, sporadic cases of thyroid disease following vaccination have been reported. We describe 19 consecutive cases of COVID vaccine-related thyroid disease. Medical records were reviewed for 9 patients with Graves' disease (GD) and 10 with Thyroiditis, all of whom were diagnosed following COVID-19 vaccination. In the GD group, the median age was 45.5 years, female/male(F/M) ratio 5:4, thyroid-stimulating immunoglobulins were elevated in seven patients. The median time from vaccination to diagnosis was 3 months. Methimazole treatment was given to all but one patient. At a median follow-up of 8.5 months from vaccination, three patients were still on methimazole, five went into remission (data were missing for one). In the Thyroiditis group, the median age was 47 years, the F/M ratio 7:3. Thyroiditis was diagnosed after the first, second, and third doses in one, two, and seven patients, respectively. The median time from vaccination to diagnosis was 2 months. TPO antibodies were positive in three patients. All patients were euthyroid off medication at the last visit. Six patients were diagnosed in the hypothyroid phase at 2.5 months from vaccination. Four resolved spontaneously at 3, 6, 4, and 8 months; the other two were treated with thyroxine at 1.5 and 2 months from vaccination and remained on treatment at their last visit, at 11.5 and 8.5 months, respectively. Thyroid disease should be included among possible complications of COVID-19 vaccine and either a late onset or delayed diagnosis should be considered.

Cancer and Mortality Risks of Graves' Disease in South Korea Based on National Data from 2010 to 2019.

This study aimed to investigate Graves' disease (GD) associated cancer and mortality risk using a Korean population-based study. We included 6435 patients with GD using the Korean National Health Insurance Service-National Sample Cohort database from 2010 to 2019. Data concerning such patients were compared in a 1:5 ratio with age- and sex-matched non-GD group (n=32,175). Eighteen subdivided types of cancer and cancers-in-total were analyzed. In addition to the mortality analysis, subgroup analyses were performed according to age and sex. After adjustment, the hazard ratio (HR) of the GD group for cancer-in-total was 1.07 (95% confidence interval [CI], 0.91-1.27), showing no difference when compared to the non-GD group. However, among different types of cancer, the thyroid cancer risk of the GD group was higher than that of the non-GD group (HR=1.70; 95% CI, 1.20-2.39). When subdivided by age and sex, the thyroid cancer risk of the GD group in males aged 20-39 years was higher than that of the non-GD group (HR=7.00; 95% CI, 1.48-33.12). The mortality risk of the GD group was not different from that of the non-GD group (HR=0.86; 95% CI, 0.70-1.05). In South Korea, patients with GD had a higher risk of thyroid cancer than the non-GD group. In particular, males aged 20-39 years with GD were more likely to have thyroid cancer than the non-GD group.

Correlation between gene polymorphisms of killer cell immunoglobulin-like receptors and their ligands and Graves' disease

Objective: To explore the relationship between gene polymorphism of killer cell immunoglobulin-like receptor (KIR) and its ligand-specific human leukocyte antigen C (HLA-C) and Graves' disease (GD). Methods: Case-control study. A total of 118 unrelated GD patients (GD group) admitted to Shandong Provincial Hospital from January 2011 to December 2017 and 108 age-and sex-matched healthy controls (healthy control group) were included. The KIR genotype and its ligand HLA-C allele were detected by polymerase chain reaction sequence-specific primers (PCR-SSP). The distribution of KIR/HLA-C gene combination in GD patients and control population was analyzed to explore its association with the occurrence of GD. Results: In GD group, there were 29 males and 89 females, aged (38±14) years. In the healthy control group, there were 28 males and 80 females, aged (37±13) years. Compared with the healthy control group, the occurrence frequency of HLA-Cw01 was higher in GD group[36.4%(43/118) vs 18.5%(20/108), P=0.003], and the occurrence frequency of HLA-Cw03 and HLA-Cw06 was lower in GD group[11.9%(14/118) vs 39.8%(43/108), P<0.001; 9.3%(11/118) vs 18.5%(20/108), P=0.045]. The frequency of KIR2DL1/HLA-C2 gene combination in GD group was lower than that in control group [17.8%(21/118) vs 34.3%(37/108), P=0.005]. Logistic regression analysis showed that KIR2DL1/HLA-C2 gene combination was a protective factor for GD occurrence (OR=0.308, 95%CI: 0.126-0.752, P=0.010). Conclusions: The polymorphism of KIR/HLA-C gene is related to GD. The low expression of KIR2DL1/HLA-C2 in GD patients may be a protective factor for GD.

Stress-Related Immune Response and Selenium Status in Autoimmune Thyroid Disease Patients.

Autoimmune thyroid disease (AITD), including Graves' disease (GD) or Hashimoto's thyroiditis (HT), occurs due to genetic susceptibility and environmental factors, among which the role of stressful events remains controversial. This study investigated the relationship between the number and impact of stressful life events in AITD patients with selenium status, and the Th1/Th2/Th17 immune response. The study population included three groups: HT (n = 47), GD (n = 13), and a control group (n = 49). Thyroid function parameters, autoantibody levels, and the plasma levels of cytokines, selenium, selenoprotein P (SeP), and glutathione peroxidase 3 (GPx) activity were measured. Participants filled out the Life Experiences Survey. No significant differences in the number of stressful life events were found among the patients with HT, GD, and the controls. A higher (median (interquartile range)) negative stress level (8 (4-12)) than a positive stress level (3 (1-9)) was found in the HT group. The HT group showed a correlation between SeP and the positive stress level: rs = -0.296, p = 0.048, and the GD group between GPx and the negative stress level (rs = -0.702, p = 0.011). Significant positive correlations between thyroid peroxidase antibody level and the total number of major life events (p = 0.023), the number of major life events in the last 7-12 months, and the number of major life events with no impact and a negative stress level were found. We suggest that the measurements of Th2-related cytokines and selenoproteins could be used as biomarkers for the development of AITD in cases where stress is considered a component cause of the pathogenic mechanism of the disease.

Platelet abnormalities in autoimmune thyroid diseases: A systematic review and meta-analysis.

Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform. The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published up to August 16th, 2022, with no restrictions on the language of the articles. Reference lists of eligible articles were also searched. A random effect model was used to pool the standardized mean difference (SMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) between AITD patients and healthy controls, and subgroup analyses were performed. A total of 19 articles with 6173 people (3824 AITD patients and 2349 healthy people) were included in the meta-analysis. The results showed that PLT and MPV values were significantly increased in AITD patients when compared with healthy people (SMD: 0.164, 95% CI: 0.044 to 0.285; SMD: 0.256, 95% CI: 0.013 to 0.500), while no significant difference was found in PDW between the AITD group and the control group (SMD: 0.060, 95% CI: -0.164 to 0.284). Subgroup analysis according to disease type and thyroid function revealed that for PLT, this difference was only found in the Hashimoto's thyroiditis (HT) and hypothyroid groups, but not in the Graves' disease (GD) and hyperthyroid groups. For MPV, the results were the opposite of those for PLT: MPV was significantly higher in the GD, hyperthyroid, and euthyroid groups than in the control group, but not in the HT and hypothyroid groups. Sensitivity analysis showed that the stability of the pooled MPV was not good. No publication bias was found. PLT and MPV are significantly elevated in patients with AITD, with PLT being more significantly elevated in HT and hypothyroidism, and MPV being more significantly increased in GD and hyperthyroidism. Appropriate clinical attention can be paid to the thyroid function of patients when abnormal platelet indices are found, and conversely, the consequences of abnormal platelet parameters such as elevated MPV lead to an increased occurrence of cardiovascular events, which should also be addressed in the AITD population. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022341823.