Monitoring thyroid volume in children allows for non-invasive, intuitive, and rapid assessment of potential thyroid disorders, facilitating early detection in large-scale screenings without blood draws. In this study, we investigated associations between urinary pesticide metabolites (organophosphate, pyrethroid, and phenoxy carboxylic acid), urinary iodine, and thyroid volume in children aged 8-11 years across Guangzhou districts, China. We compared the spatial distribution of urinary pesticide metabolites among districts and assessed health risks using probabilistic Monte Carlo simulation. We evaluated associations between thyroid volume and multiple factors: urinary iodine, demographic variables, anthropometric measures, environmental factors, and urinary creatinine. The associations between pesticide metabolites and thyroid volume were assessed using multivariable linear regression, trend tests, and restricted cubic splines. The joint effects of multiple pesticide metabolites on thyroid volume were evaluated by the Bayesian kernel machine regression. The role of urinary iodine was explored through mediation and moderation analyses. The result revealed that 0.89 % of children had risk levels of parathion exposure. Thyroid volume showed positive correlations with age and body surface area but negative correlation with urinary iodine. Two pyrethroid metabolites, cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA) and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-DCCA), demonstrated negative associations with thyroid volume after covariate adjustment. While thyroid volume decreased with higher pesticide metabolite concentrations, this joint effect was not statistically significant. The associations between thyroid volume and cis-DCCA and trans-DCCA were fully mediated by urinary iodine, but the metabolites' effects on thyroid volume remained consistent across different urinary iodine concentrations. The results indicated that pesticide exposure may influence thyroid volume through an iodine-mediated pathway and highlighted the importance of iodine status in thyroid health assessment.

Background/Objectives: Both adiposity and Hashimoto's thyroiditis (HT) are states of chronic inflammation. Adiposity may increase the risk of thyroid nodules and thyroid carcinoma. However, its role in patients with HT remains unclear. The connections among thyroid nodularity, adiposity, and HT have not been explored. Aim: To investigate the impact of adiposity on thyroid nodularity in patients with HΤ and to determine whether there are any differences in the risk for thyroid cancer. Methods: This retrospective cohort study included 294 consecutive patients with HT who were categorized according to their body mass index (BMI). Grayscale ultrasound (US) and fine-needle aspiration (FNA) cytology results were evaluated in association with clinicopathological characteristics. Results: After controlling for age and gender, nodules from patients with a BMI ≥ 25 kg/m2 showed significantly more suspicious or malignant cytology (Thy 4-5) compared to patients with a BMI < 25 kg/m2 (27.03% vs. 18.18%; p < 0.01). Although not statistically significant after adjustments, patients with BMI ≥ 25 kg/m2 demonstrated a higher proportion of nodules classified as highly suspicious on ultrasound (28.20% vs. 22.46%). Additionally, overweight and obese patients tended to have more thyroid nodules (mean ± SD: 2.91 ± 2.11) than normal-weight patients (2.36 ± 1.79), a difference approaching marginal significance (p = 0.06). Conclusions: Adiposity is associated with more suspicious and malignant cytology in patients with HT. Overweight and obese patients with HT tended to have more thyroid nodules. Further studies are needed to investigate the mechanisms linking obesity, thyroid nodules, and HT.

Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population-based pregnancy-specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population-based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity.

A total of 800 healthy pregnant women aged 20-40 years in the Bhaktapur municipality were included. Population-based reference ranges for thyroid hormones levels were defined as 2.5th and 97.5th percentiles using competitive immunoluminometric assay design. Thyroid disease cases and those with recommended treatment indications were calculated using current non-pregnancy new reference ranges. Multivariate regression analyses were performed to identify the determinants of thyroid hormones and antibody levels.

Median gestational age was 11 weeks. The reference interval was 0.05-3.69 µLU/mL for thyroid stimulating hormone (TSH) and 8.89-15.28 pg/mL for free tetraiodothyronine (fT4) after excluding thyroid peroxidase antibody-positive women. Compared with the current non-pregnancy reference ranges, the new calculations increased the number of women who required treatment from 5 to 12 (0.9% increase). We identified 19 women (2.4%) who were positive for TSH receptor antibody (TRAb). We could not identify the determinants of TRAb positivity, and TRAb positivity was not associated with TSH or fT4 levels.

We found meaningful changes using population-based pregnancy-specific TSH and fT4 reference intervals and encourage further studies in other low- and middle-income settings. Our findings suggest that population screening for TRAb is not clinically meaningful.

Clinical Trial Registration: U1111-1183-4093.

Background and aim Hashimoto's thyroiditis (HT) pathogenesis is characterized by a dysregulation of immune tolerance, which may be influenced by genetic variations in the FOXP3 gene, a key regulator of T-regulatory cell function. However, the role of specific FOXP3 polymorphisms in HT susceptibility is not yet fully understood, particularly in Middle Eastern populations. This study aims to explore the association between the FOXP3 rs2232368 polymorphism and HT susceptibility in an Iraqi population while also examining its relationship with thyroid function parameters. Methods This case-control study included 60 HT patients and 40 healthy controls from the Medical City Educational Laboratories in Baghdad (October 2022 to September 2023). HT diagnosis was based on established clinical and laboratory criteria. Thyroid function (thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4)) was measured using the mini VIDAS® system (bioMérieux, Craponne, France). FOXP3 rs2232368 genotyping was performed using ARMS-PCR. Genetic associations were assessed through ORs with 95% CIs, adjusting for demographic and clinical variables. Results HT patients exhibited significant thyroid dysfunction compared to controls (median TSH: 18.82 vs. 2.66 mIU/L, p < 0.001; T3: 0.53 vs. 2.33 nmol/L, p < 0.001; T4: 8.12 vs. 43.5 μg/dL, p < 0.001). The AA genotype was associated with a significantly increased risk of HT (OR = 4.66, 95% CI: 1.32-16.44, p = 0.017), while the heterozygous GA genotype showed a nonsignificant trend (OR = 2.28, 95% CI: 0.84-6.19, p = 0.108). The A allele was strongly associated with HT susceptibility (OR = 2.98, 95% CI: 1.54-5.77, p = 0.001). These associations remained significant after adjusting for BMI and thyroid parameters. Conclusions This study identifies FOXP3 rs2232368 as a significant genetic risk factor for HT in the Iraqi population, with the AA genotype associated with nearly a five-fold increased susceptibility. These findings enhance our understanding of the genetic basis of HT and may inform risk stratification strategies for Middle Eastern populations. Further research is needed to explore the functional implications of this polymorphism in thyroid autoimmunity.

Patients with Primary Sjögren's syndrome (pSS) are at a higher risk of thyroid disorders than the general population. This retrospective analysis of 202 patients with pSS was conducted to uncover risk factors associated with thyroid involvement and to create a predictive model for this condition.

We analyzed 202 patients with pSS from Guang'anmen Hospital, China Academy of Chinese Medical Sciences, with 105 cases of thyroid involvement and 97 without. The Least Absolute Shrinkage and Selection Operator method was used to identify key variables for our risk model. These variables were then subjected to multivariate logistic regression to develop the model. The accuracy of the model was assessed through the C-index, receiver operating characteristic curves, calibration plots, and decision curve analysis, with internal validation via bootstrapping.

High-sensitivity C-reactive protein (HCRP), pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and aspartate aminotransferase (AST) were incorporated into the nomogram. The model showed robust discrimination and calibration abilities. Decision curve analysis indicated the clinical utility of our nomogram in intervening on the probability thresholds of thyroid disease.

By integrating HCRP, pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and AST, our thyroid risk nomogram can predict the risk of thyroid involvement in patients with pSS, aiding in more informed treatment strategies.

The aim of this study was to elucidate the relationships between thyroid hormones, lifestyle factors, biochemical markers, and autoimmune thyroid disease (AITD), thereby identifying the factors influencing the development of these diseases.

The study encompassed 517 patients with AITD and 549 patients with non-autoimmune thyroid disease. Demographic and clinical data were collected, and various laboratory indicators, including urinary iodine and thyroid hormones, were measured and compared between the groups. Lasso regression was employed to select the independent variables, while logistic regression analysis determined the factors associated with the development of AITD.

The prevalence of drinking alcohol history, median urinary iodine, and TSH concentrations proved significantly greater in the AITD group compared to the control group, while FT3 levels demonstrated lower values within the AITD group (p<0.05). Furthermore, there was a significant difference in the distribution of iodine nutrition status between the two groups (p<0.05). Both univariate and multivariate logistic regression analyses revealed significant associations among excessive iodine intake, drinking alcohol history, TSH, FT3, and the development of AITD.

Excessive iodine intake and drinking alcohol history are implicated in an augmented risk of developing AITD. The prevention of AITD may necessitate the regular monitoring of TSH and FT3 concentrations.

Thyrotropin-receptor antibodies (TRAb) are used to diagnose Graves' hyperthyroidism in pregnant women. Bioassays provide a measure of thyrotropin-receptor stimulatory antibodies (TSI) specifically. The objective was to measure TSI in pregnant women for establishment of a pregnancy-specific cut-off and comparison with immunoassay measurements of TRAb.

The retrospective Danish study was performed within the North Denmark Region Pregnancy Cohort (2011-2015) that includes stored biobank samples from early pregnancy (median week 10) with immunoassay measurements of thyroid function parameters and TRAb. TSI were measured in the same samples using the Turbo TSI bioassay (Quidel/Ortho-Clinical Diagnostics) with a recommended cut-off of 0.0241 IU/L in non-pregnant adults. A pregnancy-specific TSI cut-off (95-percentile) was established using Regression on Order Statistics.

The established TSI cut-off was 0.0418 IU/L (95 % CI: 0.0417-0.0419). Among women with early pregnancy hyperthyroidism (n=438), 43 women (9.8 %) were TSI positive using the established cut-off, and these women had lower TSH (median 0.008 mIU/L) compared to women with TSI levels below 0.0241 (median TSH 0.040 mIU/L) or in the range from 0.0241 to 0.0418 (median TSH 0.033 mIU/L). Among the 438 women with early pregnancy hyperthyroidism, 22 women were positive for TSI and TRAb, 388 were negative for both, and 28 women were positive for either TSI or TRAb.

This is the first study on TSI measurements in a large cohort of early pregnant women. A pregnancy-specific cut-off for TSI was established and agreement in the classification with immunoassay measurements of TRAb was seen in 94 % of cases.

Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, represents the most prevalent autoimmune thyroid disorder globally. The potential influence of HT on the clinical and pathological attributes, as well as the clinical outcomes of differentiated thyroid carcinoma (DTC), remains a point of ongoing debate within the medical community. The central focus of this study was to analyze the influence of HT on clinico-pathological characteristics and its prognostic impact in a large cohort of DTC from Middle Eastern ethnicity. Design, Patients, Measurements. An extensive analysis involving 1822 DTC patients was conducted to determine the association with clinico-pathological characteristics as well as prognosis, using Chi-square tests and Kaplan-Meier curves.

23.9% (435/1822) of DTC patients were diagnosed with HT. Univariate analysis revealed a positive correlation between presence of HT and clinico-pathological factors such as female gender, younger age, and early stage tumor. In contrast, HT demonstrated a negative association with several aggressive clinical features, including extrathyroidal extension, distant metastasis, recurrent/persistent disease and high-risk categorization by the American Thyroid Association (ATA) guidelines. Despite HT being associated with favorable clinico-pathological features in Middle Eastern DTC patient, our study found no significant influence on overall survival or recurrence-free survival.

The finding of an association between HT and favorable clinico-pathological characteristics, but lack of impact on prognosis, underscores the complexity of HT-DTC relationship, necessitating further comprehensive research to fully understand these interactions.

The current study was conducted to assess the relationship between the STAT3 gene variants rs744166 and rs2293152 and autoimmune thyroid disorder in the Pakhtun population of the province, of Khyber Pakhtunkhwa, Pakistan. Blood was collected from 100 healthy individuals and 400 thyroid-disordered patients. Of these, one hundred were diagnosed with Hashimoto's thyroiditis (HT), while 32 were confirmed as Grave's disease (GD) patients. T3, T4, and TSH serum levels were checked to diagnose thyroid disorders. The blood was analyzed for anti-thyroid peroxidase antibodies (Anti-TPOAb) (AESKULISA- ATPO - elisa kit), (Germany), and thyroid stimulating hormone receptor antibodies (TSHRAb), TSHR Ab elisa kit (Diametra Italy), respectively. PCR was used to amplify the targeted STAT3 gene polymorphisms from rs744166 (301 bp) and rs2293152 (365 bp) sequences and then digested by specific restriction endonucleases (AluI) and AciI respectively. The disease displayed a female predominance. The genotype TC and CC of rs744166 showed a significant relationship with Grave's disease (p = 0.002, OR = 0.28, 95 % CI = 0.11-0.77) in patients. The C allele contributed significantly to the disease in GD patients. The SNP rs2293152 significantly differed between GD patients and control (p = 0.032, OR = 0.29, 95 % CI = 0.09-0.86). Similarly, the G and C alleles showed a significant (p = 0.02) difference between GD patients and the control. No significant association was found for both SNPs in Hashimoto's thyroiditis disease. It is concluded that the STAT3 gene (rs744166 and rs2293152) was found to have a potential role in autoimmunity in GD patients. Still, it needs further studies with larger sample sizes in the Pakhtun population to understand this relationship.

Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non-pregnant and pregnant adults.

Cross-sectional study.

Serum samples were obtained from 192 blood donors (non-pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease.

Each sample was used for measurement of thyroid-stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI).

In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30-1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48-1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61-1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37-2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69-3.62 mIU/L)).

Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non-pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease.

This study was conducted to evaluate the effects of different doses of selenium (Se) from Sel-Plex© (selenium-enriched Saccharomyces cerevisiae yeast) supplement on the antioxidant status, the antibody titers against the foot-and-mouth disease virus, and the expression of interleukin-2 (IL-2) and interferon-γ (IFN-γ) genes in ewes during the hot season. Six ewes were kept at 25 °C and received basal diet (the negative control group), and 24 ewes were kept at 38 °C for 5 h per day and received no supplement (the positive control), 0.15, 0.30, and 0.45 mg Se/kg. Ewes in the positive control had higher (P<0.001) liver enzyme activity, malondialdehyde (MDA), and cortisol levels, and lower antibody titer than the negative control. The liver enzymes' lowest (P<0.001) activities were observed in ewes receiving 0.30 and 0.45 mg Se/kg. Ewes receiving 0.30 and 0.45 mg Se/kg had lower MDA levels than other treatments. Ewes receiving 0.30 and 0.45 mg Se/kg had higher (P<0.001) total antioxidant capacity levels than those receiving 0.15 mg Se/kg and the positive control. Se-supplemented groups had lower (P<0.001) relative expression of IL-2 and higher (P<0.04) expression of IFN-γ than the positive control. The antibody titer was the same in the positive control and the group receiving 0.15 mg Se/kg. Ewes fed a diet with 0.30 and 0.45 mg Se/kg had higher (P<0.011) antibody titer than the positive control. The Se supplementation can reverse the decrease of antioxidant capacity and immune function caused by heat stress, and 0.3 mg Se/kg from Sel-Plex©is the best dose.

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease characterized by T lymphocyte-mediated destruction of thyroid follicles. To study the pathogenesis of HT and the efficacy of new substances for its treatment, an easily obtained and adequate to the human disease experimental model is needed. The aim of our study was to find out whether it is possible to induce experimental autoimmune thyroiditis (EAT) similar to Hashimoto's thyroiditis by injecting with thyroglobulin (Tg) without using agents that enhance its thyroiditogenicity and without taking into account the genetic sensitivity of animals.

Wistar rats were immunized with freshly isolated rat Tg or porcine Tg. In 8 weeks, histological studies of the thyroid and parathyroid glands were performed. Thyroid function and total serum calcium level were also evaluated.

Immunization with both rat and porcine freshly isolated Tg caused T lymphocytic infiltration of the thyroid gland, thyroid follicle atrophy and degradation in Wistar rats. EAT caused by porcine Tg was characterized by greater severity than EAT induced with rat Tg. In 55% of rats with porcine Tg-induced EAT, oxyphilic metaplasia was detected in the parathyroid glands. In addition, low total serum calcium was observed in these rats.

Two rat models of autoimmune thyroiditis were obtained. EAT caused in Wistar rats by immunization with rat Tg is similar to Hashimoto's thyroiditis. EAT induced with porcine Tg was accompanied by oxyphil cell metaplasia in the parathyroids and hypocalcemia.

Considering the possible adverse effects of thyroid autoantibodies on the brain, the present study aimed to investigate whether there was a difference in mental health difficulties and mindfulness awareness levels between subclinical Hashimoto's thyroiditis patients with and without levothyroxine (LT4) use. A case-control study was conducted. The Strengths and Difficulties Questionnaire (SDQ) and the Mindful Attention Awareness Scale (MAAS) were used to screen mental health difficulties and mindfulness awareness. Scale scores were compared by performing correlation analysis between the groups with respect to LT4 use and thyroid autoantibodies. Levothyroxine alone does not affect scale results. Higher thyroid peroxidase antibody (TPOAb) titers were positively correlated with the behavioral problems subscale of the SDQ, while awareness level in patients was inversely correlated with higher thyroglobulin antibody (TgAb) levels.

Autoimmune thyroid disease (AITD) is the most common organic specific illness of the thyroid gland. It may manifest as the overproduction or the decline of thyroxine and triiodothyronine. Hyperthyroidism develops due to the overproduction of hormones as an answer to the presence of stimulatory antibodies against the TSH receptor. Hashimoto's thyroiditis (HT) is generally characterized by the presence of thyroid peroxidase and thyroglobulin antibodies, with a concomitant infiltration of lymphocytes in the thyroid. Due to the progressive destruction of cells, AITD can lead to subclinical or overt hypothyroidism. Pathophysiology of AITD is extremely complicated and still not fully understood, with genetic, environmental and epigenetic factors involved in its development. Due to increasing incidence and social awareness of this pathology, there is an urgent need to expand the background concerning AITD. A growing body of evidence suggests possible ways of treatment apart from traditional approaches. Simultaneously, the role of potential new biomarkers in the diagnosis and monitoring of AITD has been highlighted recently, too. Therefore, we decided to review therapeutic trends in the course of AITD based on its pathophysiological mechanisms, mainly focusing on HT. Another aim was to summarize the state of knowledge regarding the role of new biomarkers in this condition.

Metformin is a synthetic biguanide used as an antidiabetic drug in type 2 diabetes mellitus, achieved by studying the bioactive metabolites of Galega officinalis L. It is also used off-label for various other diseases, such as subclinical diabetes, obesity, polycystic ovary syndrome, etc. In addition, metformin is proposed as an add-on therapy for several conditions, including autoimmune diseases, neurodegenerative diseases, and cancer. Although metformin has been used for many decades, it is still the subject of many pharmacodynamic and pharmacokinetic studies in light of its extensive use. Metformin acts at the mitochondrial level by inhibiting the respiratory chain, thus increasing the AMP/ATP ratio and, subsequently, activating the AMP-activated protein kinase. However, several other mechanisms have been proposed, including binding to presenilin enhancer 2, increasing GLP1 release, and modification of microRNA expression. Regarding its pharmacokinetics, after oral administration, metformin is absorbed, distributed, and eliminated, mainly through the renal route, using transporters for cationic solutes, since it exists as an ionic molecule at physiological pH. In this review, particular consideration has been paid to literature data from the last 10 years, deepening the study of clinical trials inherent to new uses of metformin, the differences in effectiveness and safety observed between the sexes, and the unwanted side effects. For this last objective, metformin safety was also evaluated using both VigiBase and EudraVigilance, respectively, the WHO and European databases of the reported adverse drug reactions, to assess the extent of metformin side effects in real-life use.

Our article examines a rare case where hypothyroidism due to Hashimoto's thyroiditis progressed, after a long period (three years) of L-thyroxine substitution, into confirmed hyperthyroidism due to Graves' disease in a 69-year-old man. The article explores possible mechanisms of this unusual transition based on our case and others reported in the literature. Findings suggest that the coexistence of Hashimoto's thyroiditis and Graves' disease can lead to transitions between hypothyroidism and hyperthyroidism, influenced by the predominance of involved antibodies and residual capacity of thyroid tissue. The authors emphasize the importance of further studies to better understand these transitions and identify at-risk patients. In conclusion, the article highlights the necessity of considering the rare possibility of transition to Graves' disease in patients presenting with persistent hyperthyroidism despite cessation of L-thyroxine.

In recent years, mounting evidence has indicated a co-morbid relationship between hypothyroidism and rheumatoid arthritis (RA), however, the shared genetic factors underlying this association remain unclear. This study aims to investigate the common genetic architecture between hypothyroidism and RA.

Genome-wide association study (GWAS) summary statistics from recently published studies were utilized to examine the genetic correlation, shared genetic loci, and potential causal relationship between hypothyroidism and RA. Statistical methods included linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), cross-trait meta-analyses, colocalization analysis, multi-marker analysis of genomic annotation (MAGMA), tissue-specific enrichment analysis (TSEA), functional enrichment analysis, and latent causal variable method (LCV).

Our study demonstrated a significant genetic correlation between hypothyroidism and RA(LDSC:rg=0.3803,p=7.23e-11;HDL:rg=0.3849,p=1.02e-21). Through cross-trait meta-analysis, we identified 1035 loci, including 43 novel genetic loci. By integrating colocalization analysis and the MAGMA algorithm, we found a substantial number of genes, such as PTPN22, TYK2, and CTLA-4, shared between the two diseases, which showed significant enrichment across 14 tissues. These genes were primarily associated with the regulation of alpha-beta T cell proliferation, positive regulation of T cell activation, positive regulation of leukocyte cell-cell adhesion, T cell receptor signaling pathway, and JAK-STAT signaling pathway. However, our study did not reveal a significant causal association between the two diseases using the LCV approach.

Based on these findings, there is a significant genetic correlation between hypothyroidism and RA, suggesting a shared genetic basis for these conditions.

Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto disease (HD), which often run in the same family. AITD etiology is incompletely understood: Genetic factors may account for up to 75% of phenotypic variance, whereas epigenetic effects (including DNA methylation [DNAm]) may contribute to the remaining variance (eg, why some individuals develop GD and others HD).

This work aimed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) comparing GD to HD.

Whole-blood DNAm was measured across the genome using the Infinium MethylationEPIC array in 32 Australian patients with GD and 30 with HD (discovery cohort) and 32 Danish patients with GD and 32 with HD (replication cohort). Linear mixed models were used to test for differences in quantile-normalized β values of DNAm between GD and HD and data were later meta-analyzed. Comb-p software was used to identify DMRs.

We identified epigenome-wide significant differences (P < 9E-8) and replicated (P < .05) 2 DMPs between GD and HD (cg06315208 within MDC1 and cg00049440 within KLF9). We identified and replicated a DMR within CUTA (5 CpGs at 6p21.32). We also identified 64 DMPs and 137 DMRs in the meta-analysis.

Our study reveals differences in DNAm between GD and HD, which may help explain why some people develop GD and others HD and provide a link to environmental risk factors. Additional research is needed to advance understanding of the role of DNAm in AITD and investigate its prognostic and therapeutic potential.

Autoimmune thyroiditis (AITD) is a T-cell-mediated, organ- specific autoimmune disease caused by interactions between genetic and environmental factors. Patients with AITD show thyroid lymphocyte infiltration and an increase in the titer of thyroid autoimmune antibodies, thereby altering the integrity of thyroid follicle epithelial cells and dysregulating their metabolism and immune function, leading to a decrease in multi-tissue metabolic activity. Research has shown that patients with AITD have a significantly higher risk of adverse pregnancy outcomes, such as infertility and miscarriage. Levothyroxine(LT4) treatment can improve the pregnancy outcomes of normal pregnant women with thyroid peroxidase antibodies(TPOAb) positivity, but it is not effective for invitro fertilization embryo transfer (IVF-ET) in women with normal thyroid function and positive TPOAb. Other factors may also influence pregnancy outcomes of patients with AITD. Recent studies have revealed that the gut microbiota participates in the occurrence and development of AITD by influencing the gut-thyroid axis. The bacterial abundance and diversity of patients with Hashimoto thyroiditis (HT) were significantly reduced, and the relative abundances of Bacteroides, fecal Bacillus, Prevotella, and Lactobacillus also decreased. The confirmation of whether adjusting the composition of the gut microbiota can improve pregnancy outcomes in patients with AITD is still pending. This article reviews the characteristics of the gut microbiota in patients with AITD and the current research on its impact in pregnancy.

There is still controversy regarding the relationship between hypothyroidism and rheumatoid arthritis (RA), and there has been a dearth of studies on this association. The purpose of our study was to explore the shared genetic architecture between hypothyroidism and RA.

Using public genome-wide association studies summary statistics of hypothyroidism and RA, we explored shared genetics between hypothyroidism and RA using linkage disequilibrium score regression, ρ-HESS, Pleiotropic analysis under a composite null hypothesis (PLACO), colocalization analysis, Multi-Trait Analysis of GWAS (MTAG), and transcriptome-wide association study (TWAS), and investigated causal associations using Mendelian randomization (MR).

We found a positive genetic association between hypothyroidism and RA, particularly in local genomic regions. Mendelian randomization analysis suggested a potential causal association of hypothyroidism with RA. Incorporating gene expression data, we observed that the genetic associations between hypothyroidism and RA were enriched in various tissues, including the spleen, lung, small intestine, adipose visceral, and blood. A comprehensive approach integrating PLACO, Bayesian colocalization analysis, MTAG, and TWAS, we successfully identified TYK2, IL2RA, and IRF5 as shared risk genes for both hypothyroidism and RA.

Our investigation unveiled a shared genetic architecture between these two diseases, providing novel insights into the underlying biological mechanisms and establishing a foundation for more effective interventions.

Systemic sclerosis, also referred to as scleroderma, is a chronic autoimmune disease that affects both internal organs and the skin. Systemic sclerosis predominantly affects female patients and can coexist with other disorders, including those affecting the thyroid gland. Common symptoms such as fatigue and weight changes can be attributed to either systemic sclerosis or thyroid disease. In this comprehensive review, an extensive analysis is conducted using research from 2002 to 2022, sourced from PubMed. The main focus of this exploration is to understand the intricate relationship between thyroid disorders and systemic sclerosis. We obtained these results by analyzing a number of 32285 patients included in 21 original studies. The existing evidence suggests that there is a higher incidence of elevated TSH levels and hypothyroidism in patients with systemic sclerosis, particularly in females, compared to the general population. This remains true even when comparing patients from iodine-deficient regions. Additionally, there is an increased occurrence of hyperthyroidism in the context of systemic sclerosis, which negatively impacts the prognosis of these patients. Furthermore, thyroid antibodies, predominantly anti-thyroid peroxidase (anti-TPO) antibodies, and autoimmune disorders are more commonly observed in individuals with systemic sclerosis. Although thyroid nodules are not specifically linked to the disease, when considering thyroid volume, it is observed that the thyroid gland in systemic sclerosis patients has a decreased volume, possibly due to fibrosis. Conversely, other studies have revealed that patients without autoimmune thyroid diseases (AITDs) are more likely to have a history of digital ulcers, pulmonary fibrosis detected by computed tomography scan, and a requirement for immunosuppressive medication. The majority of the studies did not establish a connection between thyroid disease in these patients and the occurrence of the limited or diffuse forms of systemic sclerosis, as well as the presence of digital ulcers, calcinosis, pulmonary arterial hypertension, scleroderma renal crisis, Raynaud phenomenon, and various other clinical manifestations.

In this narrative review, we aimed to overview the interplay between lichen planus (LP) and thyroid conditions (TCs) from a dual perspective (dermatologic and endocrine), since a current gap in understanding LP-TC connections is found so far and the topic is still a matter of debate. We searched PubMed from Inception to October 2023 by using the key terms "lichen planus" and "thyroid", (alternatively, "endocrine" or "hormone"). We included original clinical studies in humans according to three sections: LP and TC in terms of dysfunction, autoimmunity, and neoplasia. Six studies confirmed an association between the thyroid dysfunction (exclusively hypothyroidism) and LP/OL (oral LP); of note, only one study addressed cutaneous LP. The sample size of LP/OLP groups varied from 12-14 to 1500 individuals. Hypothyroidism prevalence in OLP was of 30-50%. A higher rate of levothyroxine replacement was identified among OLP patients, at 10% versus 2.5% in controls. The highest OR (odd ratio) of treated hypothyroidism amid OLP was of 2.99 (p < 0.005). Hypothyroidism was confirmed to be associated with a milder OLP phenotype in two studies. A single cohort revealed a similar prevalence of hypothyroidism in LP versus non-LP. Non-confirmatory studies (only on OLP, not cutaneous LP) included five cohorts: a similar prevalence of hypothyroidism among OLP versus controls, and a single cohort showed that the subjects with OLP actually had a lower prevalence of hypothyroidism versus controls (1% versus 4%). Positive autoimmunity in LP/OLP was confirmed in eight studies; the size of the cohorts varied, for instance, with 619 persons with LP and with 76, 92, 105, 108, 192, 247, and 585 patients (a total of 1405) with OLP, respectively; notably, the largest control group was of 10,441 individuals. Four clusters of approaches with respect to the autoimmunity in LP/OLP were found: an analysis of HT/ATD (Hashimoto's thyroiditis/autoimmune thyroid diseases) prevalence; considerations over the specific antibody levels; sex-related features since females are more prone to autoimmunity; and associations (if any) with the clinical aspects of LP/OLP. HT prevalence in OLP versus controls was statistically significantly higher, as follows: 19% versus 5%; 12% versus 6%; and 20% versus 9.8%. A single study addressing LP found a 12% rate of ATDs. One study did not confirm a correlation between OLP-associated clinical elements (and OLP severity) and antibody values against the thyroid, and another showed that positive TPOAb (anti-thyroperoxidase antibodies) was more often found in erosive than non-erosive OLP (68% versus 33%). Just the reverse, one cohort found that OLP subjects had a statistically significantly lower rate of positive TPOAb versus controls (9% versus 15%). Five case-control studies addressed the issue of levothyroxine replacement for prior hypothyroidism in patients that were diagnosed with OLP (no study on LP was identified); three of them confirmed a higher rate of this treatment in OLP (at 8.9%, 9.7%, and 10.6%) versus controls. In conclusion, with regard to LP/OLP-TC, we note several main aspects as practical points for multidisciplinary practitioners: OLP rather than LP requires thyroid awareness; when it comes to the type of thyroid dysfunction, mostly, hypothyroidism should be expected; female patients are more prone to be associated with ATDs; a potential higher ratio of OLP subjects taking levothyroxine was found, thus a good collaboration with an endocrinology team is mandatory; and so far, OLP individuals have not been confirmed to be associated with a higher risk of thyroid nodules/cancer.

Autoimmune thyroid disorders (AITD) represent the most frequent of all autoimmune disorders. Their aetiopathogenesis is incompletely understood, but most likely multifactorial. Early life stress can have long-lasting effects on the immune system. The aim of the present study was to investigate, for the first time, whether patients with AITD are more frequently affected by early life stress. A total of N = 208 women were recruited into a case-control study. Of these, n = 78 (median age: 53, interquartile range: 15) were patients recruited from a thyroid outpatient clinic with confirmed Hashimoto's thyroiditis, Graves' disease, or AITD not otherwise specified. The remaining n = 130 age- and BMI-matched women (median age: 53, interquartile range: 12) were recruited from the general population. Early life stress was measured with the Childhood Trauma Questionnaire. Patients with AITD did not differ from controls regarding sexual abuse, physical abuse, and physical neglect. However, a greater number of patients reported emotional neglect (29.7% vs. 19.5%) and emotional abuse (41.3% vs. 32%). This study provides initial evidence for emotional neglect and abuse as potential risk factors for the development of AITD. Prospective confirmation of these findings could pave the way for the development of interventions to prevent AITD in predisposed individuals.

Review the historical context of research and changing therapeutic landscape of thyroid-associated ophthalmopathy (TAO) by focusing on the relationship between TAO, CD34+ fibrocytes, thyrotropin receptor (TSHR), and insulin-like growth factor-I receptor (IGF-IR).

A literature review using search terms, including fibrocytes, IGF-IR, TSHR, TAO, and thyroid eye disease.

The mechanisms involved in TAO have been partially identified. Substantial progress has been made over several decades, including 1) recognizing the interplay between the professional immune system and orbital tissues; 2) TSHR and IGF-IR act interdependently in mediating the pathogenesis of TAO; 3) Multiple cytokines and specific immune cells are involved in activating and remodeling orbital tissue; 4) Recognition of these mechanisms is allowing the development of target therapies such as teprotumumab, a monoclonal antibody IGF-IR inhibitor approved by the US Food and drug administration for treatment of TAO; and 5) It appears that teprotumumab acts on the systemic immune system peripheral to the orbit.

Additional molecules targeting IGF-IR and other plausible disease mechanisms are currently under development. This activity in the TAO therapeutic space portends even greater improvements in patient care.

The causal relationship between Rheumatoid arthritis (RA) and hypothyroidism/hyperthyroidism remains controversial due to the limitations of conventional observational research, such as confounding variables and reverse causality. We aimed to examine the potential causal relationship between RA and hypothyroidism/hyperthyroidism using Mendelian randomization (MR).

We conducted a bidirectional two-sample univariable analysis to investigate the potential causal relationship between hypothyroidism/hyperthyroidism and RA. Furthermore, we performed a multivariate analysis to account for the impact of body mass index (BMI), smoking quantity, and alcohol intake frequency.

The univariable analysis indicated that RA has a causative influence on hypothyroidism (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.01-1.14, P=0.02) and hyperthyroidism (OR=1.32, 95% CI=1.15-1.52, P<0.001). When hypothyroidism/hyperthyroidism was considered as an exposure variable, we only observed a causal relationship between hypothyroidism (OR=1.21, 95% CI=1.05-1.40, P=0.01) and RA, whereas no such connection was found between hyperthyroidism (OR=0.91, 95% CI=0.83-1.01, P=0.07) and RA. In the multivariate MR analyses, after separately and jointly adjusting for the effects of daily smoking quantity, alcohol intake frequency, and BMI, the causal impact of RA on hypothyroidism/hyperthyroidism and hypothyroidism on RA remained robust. However, there is no evidence to suggest a causal effect of hyperthyroidism on the risk of RA (P >0.05).

Univariate and multivariate MR analyses have validated the causal association between RA and hypothyroidism/hyperthyroidism. Hypothyroidism confirmed a causal relationship with RA when employed as an exposure variable, whereas no such relationship was found between hyperthyroidism and RA.

Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves' disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs' functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD.

Hashimoto's thyroiditis (HT), a common form of thyroid autoimmunity, is strongly associated with deteriorating clinical status and impaired quality of life. The escalating global prevalence, coupled with the complexity of disease mechanisms, necessitates a comprehensive, bibliometric analysis to elucidate the trajectory, hotspots, and future trends in HT research.

This study aims to illuminate the development, hotspots, and future directions in HT research through systematic analysis of publications, institutions, authors, journals, references, and keywords. Particular emphasis is placed on novel treatment strategies for HT and its complications, highlighting the potential role of genetic profiling and immunomodulatory therapies.

We retrieved 8,726 relevant documents from the Web of Science Core Collection database spanning from 1 January 1990 to 7 March 2023. Following the selection of document type, 7,624 articles were included for bibliometric analysis using CiteSpace, VOSviewer, and R software.

The temporal evolution of HT research is categorized into three distinct phases: exploration (1990-1999), rapid development (1999-2000), and steady growth (2000-present). Notably, the United States, China, Italy, and Japan collectively contributed over half (54.77%) of global publications. Among the top 10 research institutions, four were from Italy (4/10), followed by China (2/10) and the United States (2/10). Recent hotspots, such as the roles of gut microbiota, genetic profiling, and nutritional factors in HT management, the diagnostic dilemmas between HT and Grave's disease, as well as the challenges in managing HT complicated by papillary thyroid carcinoma and type 1 diabetes mellitus, are discussed.

Although North America and Europe have a considerable academic impact, institutions from emerging countries like China are demonstrating promising potential in HT research. Future studies are anticipated to delve deeper into the differential diagnosis of HT and Grave's disease, the intricate relationship between gut microbiota and HT pathogenesis, clinical management of HT with papillary thyroid carcinoma or type 1 diabetes, and the beneficial effects of dietary modifications and micronutrients supplementation in HT. Furthermore, the advent of genetic profiling and advanced immunotherapies for managing HT offers promising avenues for future research.

Selenium (Se) is an essential trace element that plays an important role in thyroid physiology. Se supplementation can reduce levels of autoimmune thyroid antibodies, which may be beneficial in Hashimoto's thyroiditis (HT). However, the long-term benefits of Se supplementation for HT patients are controversial and there is no clear clinical evidence to support it, so further basic and clinical research is needed. The effect of Se on immune cells, especially T cells, in autoimmune thyroiditis (AIT) has not been elucidated. Here, we replicated a mouse model of experimental autoimmune thyroiditis (EAT) on a high-iodine diet and treated it with Se supplementation. At week 8 of the experiment, Se supplementation reduced the destruction of thyroid follicles and the infiltration rate of lymphocytes in EAT mice, and reversed the disturbance of peripheral blood thyroxine and thyroid autoantibody levels. Further examination revealed that Se had broad effects on T-cell subsets. Its effects include reducing the production of pro-inflammatory cytokines by Th1 cells, inhibiting the differentiation and production of cytokines by Th2 and Th17 cells, and upregulating the differentiation and production of cytokines by Treg cells. These changes help alleviate thyroid follicle damage during EAT. In conclusion, selenium supplementation has the potential to improve the prognosis of AIT by altering the subset differentiation and/or function of CD4+ T cells.

Thyroid hormone affects every human organ system and is a vital component of metabolism. Common and easily treatable, hypothyroidism does not usually require emergency management. However, myxedema coma is the decompensated form of hypothyroidism and can be life threatening if not treated expediently.

In the present study, it was aimed to evaluate whether there is an objective tongue image indicator that could be used to evaluate malignant risk of thyroid nodules through a cross sectional study. From December 2018 to December 2020, the TFDA-1 digital tongue-face diagnostic instrument was used to collect the tongue images. TDAS 2.0 software was used for tongue image analysis. A standardized database was constructed by combining patient physical examination results and tongue image analysis results. The relationship between tongue image index and TI-RADS classification of thyroid nodules was tested. A total of 5,900 cases were collected and 4,615 cases were included in the present study after excluding 154 cases due to incomplete information, 1,221 cases with thyroid nodules were separated into 417 cases TI-RADS 2 group, 693 cases in TI-RADS 3 group and 111 cases in TI-RADS 4 group. Without considering confounding factors, tongue image indexes zhiCon, zhiASM, zhiENT, zhiMEAN, zhiClrB, zhiClrR, zhiClrG, zhiClrI, zhiClrL and zhiClrY were significantly different among the three groups (P<0.05). Excluding the influence of age, sex, body mass index, smoking and drinking, the results of one-way variance linear trend analysis showed that the values of zhiCon, zhiENT and zhiMEAN increased with the increasing TI-RADS category, while the values of zhiASM decreased with the increase of TI-RADS category. Tongue texture index may be helpful for differentiating the benign and malignant of thyroid nodules.

Thyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles.

This hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman's correlation was done to determine the association between variables.

Out of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal.

The rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal.

Autoimmune thyroid diseases are on the rise worldwide, and such a rapid increase is mainly driven by environmental factors related to changed lifestyles in "modern" societies. In this context, diet seems to play a crucial role. An unhealthy high-energy diet, rich in animal fat and proteins, salt and refined sugars (the so-called "Western diet") negatively influences the risk of autoimmunity by altering the immune balance and the gut microbiota composition, enhancing oxidative stress and promoting inflammation. In contrast, the Mediterranean diet represents a unique model of healthy eating, characterized by a high intake of food from vegetable sources, a low consumption of saturated fats in favor of unsaturated fats (mainly, olive oil), a moderate consumption of fish (typically, the small oily fishes) and dairy products, as well as a moderate consumption of wine at meals, and a low intake of meat. Thanks to its nutritional components, the Mediterranean Diet positively influences immune system function, gut microbiota composition, and redox homeostasis, exerting anti-oxidants, anti-inflammatory, and immunomodulatory effects. The present review was aimed at exploring the existing knowledge on the correlations between dietary habits and thyroid autoimmunity, to evaluate the role of the Mediterranean diet as a protective model.

Hashimoto's thyroiditis (HT) is one of the most common autoimmune disorders; however, its underlying pathological mechanisms remain unclear. Although aberrant glycosylation has been implicated in the N-glycome of immunoglobulin G (IgG), changes in serum proteins have not been comprehensively characterized. This study aimed to investigate glycosylation profiles in serum samples depleted of highly abundant proteins from patients with HT and propose the potential functions of glycoproteins for further studies on the pathological mechanisms of HT.

A lectin microarray containing 70 lectins was used to detect and analyze glycosylation of serum proteins using serum samples (N=27 HT; N=26 healthy control [HC]) depleted of abundant proteins. Significant differences in glycosylation status between HT patients and the HC group were verified using lectin blot analysis. A lectin-based pull-down assay combined with mass spectrometry was used to investigate potential glycoproteins combined with differentially present lectins, and an enzyme-linked immunosorbent assay (ELISA) was used to identify the expression of targeted glycoproteins in 131 patients with papillary thyroid carcinoma (PTC), 131 patients with benign thyroid nodules (BTN) patients, 130 patients with HT, and 128 HCs.

Compared with the HC group, the majority of the lectin binding signals in HT group were weakened, while the Vicia villosa agglutinin (VVA) binding signal was increased. The difference in VVA binding signals verified by lectin blotting was consistent with the results of the lectin microarray. A total of 113 potential VVA-binding glycoproteins were identified by mass spectrometry and classified by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses. Using ELISA, we confirmed that lactoferrin (LTF) and mannan-binding lectin-associated serine protease 1 (MASP-1) levels were elevated in the serum of patients with HT and PTC.

Following depletion of abundant proteins, remaining serum proteins in HT patients exhibited lower glycosylation levels than those observed in HCs. An increased level of potential VVA-binding glycoproteins may play an important role in HT development. LTF and MASP-1 expression was significantly higher in the serum of HT and PTC patients, providing novel insight into HT and PTC.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is characterized by immune system dysregulation after exposure to adjuvants, such as aluminum. Although cases of autoimmune thyroid diseases caused by ASIA have been reported, Graves' disease is one of the rarer diseases. There are some reports that vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause ASIA. Here, we describe a case of Graves' disease following SARS-CoV-2 vaccination and a review of the literature.

A 41-year-old woman was admitted to our hospital because of palpitations and fatigue. Two weeks after receiving the second SARS-CoV-2 vaccine (BNT162b2, Coronavirus Modified Uridine messenger RNA (mRNA) Vaccine, Pfizer), she developed fatigue and gradually worsened. On admission, she exhibited thyrotoxicosis (thyroid-stimulating hormone (TSH) < 0.01 mIU/L (0.08-0.54), free triiodothyronine (FT3) 33.2 pmol/L (3.8-6.3), and free thyroxine (FT4) 72.1 pmol/L (11.6-19.3)) and palpitations associated with atrial fibrillation. TSH receptor antibody (TRAb) was positive (TRAb 5.0 IU/L (< 2.0)), and ^99mTc scintigraphy showed diffuse uptake in the thyroid gland, suggesting that the thyrotoxicosis in this case was caused by Graves' disease. Thiamazole was prescribed to correct her condition, and soon after this treatment was initiated, her symptoms and thyroid hormone levels were significantly reduced.

This case report reinforces the potential correlation between ASIA affecting the thyroid and SARS-CoV-2 mRNA vaccines. The clinical course suggests that it is essential to consider the possibility of developing ASIA, such as Graves' disease, after exposure to the SARS-CoV-2 vaccine.

Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration. OA usually manifests as joint pain, limited mobility, and joint effusion. Currently, the primary OA treatment is non-steroidal anti-inflammatory drugs (NSAIDs). Although they can alleviate the disease's clinical symptoms and signs, the drugs have some side effects. Selenium nanoparticles (SeNPs) may be an alternative to relieve OA symptoms.

We confirmed the anti-inflammatory effect of selenium nanoparticles (SeNPs) in vitro and in vivo experiments for OA disease in this study. In vitro experiments, we found that SeNPs could significantly reduce the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the major inflammatory factors, and had significant anti-inflammatory and anti-arthritic effects. SeNPs can inhibit reactive oxygen species (ROS) production and increased glutathione peroxidase (GPx) activity in interleukin-1beta (IL-1β)-stimulated cells. Additionally, SeNPs down-regulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) expressions, while up-regulated type II collagen (COL-2) and aggrecan (ACAN) expressions stimulated by IL-1β. The findings also indicated that SeNPs may exert their effects through suppressing the NF-κB p65 and p38/MAPK pathways. In vivo experiments, the prevention of OA development brought on by SeNPs was demonstrated using a DMM model.

Our results suggest that SeNPs may be a potential anti-inflammatory agent for treating OA.

Evidence suggests that selenium supplementation could be useful in the treatment of Hashimoto thyroiditis (HT), but the available trials are heterogeneous. This study investigates clinically relevant effects of selenium supplementation in patients with HT.

A systematic search was performed in PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. The latest update was performed on December 3, 2022. We investigated the changes in thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) after selenium supplementation. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs).

After screening and full-text assessment, 7 controlled trials comprising 342 patients were included in the systematic review. The results showed that there was no significant change in TPOAb levels (WMD = -124.28 [95% CI: -631.08 to 382.52], P = .631, I2 = 94.5%) after 3 months of treatment. But there was a significant decrease in TPOAb levels (WMD = -284.00 [95% CI: -553.41 to -14.60], P < .05, I2 = 93.9%) and TgAb levels (WMD = -159.86 [95% CI: -293.48 to -26.24], P < .05, I2 = 85.3%) after 6 months of treatment.

Selenium supplementation reduces serum TPOAb and TgAb levels after 6 months of treatment in patients with HT, but future studies are warranted to evaluate health-related quality or disease progression.

Vitamin D insufficiency is a global health problem affecting healthy and diseased individuals, including patients with Hashimoto's thyroiditis (HT). Identifying dietary factors that may affect vitamin D levels and providing dietary guidelines accordingly can alleviate this problem. We therefore aimed to identify still unknown associations of dietary patterns, assessed through the Food Frequency Questionnaire (FFQ) with vitamin D blood levels.

FFQ was collected from 459 patients from Croatian Biobank of Patients with Hashimoto's thyroiditis (CROHT), while total 25(OH)D was measured from their stored serum samples. We performed linear regression analysis between vitamin D levels and weekly intake of 24 food groups in 459 patients with HT (ALL), and in two disease-severity groups (MILD and OVERT).

The main results of our study are observations of: (1) an inverse association between vitamin D levels and coffee consumption (ALL: β = -0.433, p = 0.005; OVERT: β = -0.62, p = 0.008); (2) an inverse association between vitamin D levels and sweets consumption (ALL: β = -0.195, p = 0.034; OVERT: β = -0.431, p = 0.006); (3) positive association between vitamin D levels and vegetable consumption (ALL: β = 0.182, p = 0.019; OVERT, β = 0.311, p = 0.009). Importantly, effect sizes of all three associations were more prominent in HT patients with prolonged and more severe disease (OVERT).

Further research into the functional and causal relationships of the observed associations is important to provide guidance regarding coffee/sugar intake on vitamin D status. A well-balanced diet can help prevent vitamin D deficiency and improve the quality of life of patients with HT, especially those in later stages of disease characterized by greater metabolic imbalance.

In 15-20% of cases, Graves' disease (GD) shifts to Hashimoto's thyroiditis (HT), while the shift from HT to GD is rare. We present a case of a patient in whom HT shifted to GD, along with a literature review. A 50-year-old woman with myxedema was diagnosed with Hashimoto's disease due to hypothyroidism and the presence of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb); she also had thyroid stimulating antibodies (TSAb) without any signs of GD. Although thyroid hormone replacement therapy improved her thyroid function, 2 months later, hyperthyroidism appeared and did not improve after discontinuation of the replacement therapy. The patient was diagnosed with GD, which improved with antithyroid agent administration. To date, only 50 cases regarding conversion from HT to GD have been reported. The median age is 44 years (range, 23-82 years), and the median time of conversion is 7 years (range, 0.1-27 years). The male-to-female ratio of HT conversion to GD is 1:9, closer to that of regular GD (1:10) than that of general HT (1:18). All patients received thyroid hormone replacement therapy for hypothyroidism due to HT. Continuous evaluation of TSAb levels is recommended in HT, particularly in cases of TSAb-positive and those under replacement, since it may help predict conversion to GD. Evaluating the clinical characteristics of patients with HT preceding GD is crucial to ensure appropriate treatment and reduce the risk of adverse events.

The most common cause of acquired thyroid dysfunction is autoimmune thyroid disease, which is an organ-specific autoimmune disease with two presentation phenotypes: hyperthyroidism (Graves-Basedow disease) and hypothyroidism (Hashimoto's thyroiditis). Hashimoto's thyroiditis is distinguished by the presence of autoantibodies against thyroid peroxidase and thyroglobulin. Meanwhile, autoantibodies against the TSH receptor have been found in Graves-Basedow disease. Numerous susceptibility genes, as well as epigenetic and environmental factors, contribute to the pathogenesis of both diseases. This review summarizes the most common genetic, epigenetic, and environmental mechanisms involved in autoimmune thyroid disease.

Autoimmune thyroid disease, encompassing Graves' disease and Hashimoto's thyroiditis, has a very complex etiology. Pathogenesis of the disease involves both genetic susceptibility and environmental triggers. Traditionally, imbalance of T helper cell 1 and 2 was thought to result in the immune disorders in Graves' disease and Hashimoto's thyroiditis. However, increasing evidence recently revealed the important role of T helper 17 cell and its relative cellular and secretory components in the pathogenesis and progression of autoimmune thyroid disease. This review is aimed to summarize the published studies on the involvement of T helper 17 cell in autoimmune thyroid disease and discuss the underlying regulatory mechanisms, which could possibly serve as the foundation of discovering new therapeutic targets.

Graves' disease (GD) is a heterogeneous autoimmune disease affecting with varying degrees of severity the thyroid gland, orbital tissues and skin. The pathogenesis of GD involves a complex interplay between multiple genetic, environmental and endogenous factors. Although the genetic predisposition to GD is well established, the significance of genotype-phenotype correlations and the role of epigenetic modifications in the disease pathogenesis remains largely unknown. In this review, we provide an up-to-date overview of genotype-phenotype correlations and summarize possible clinical implications of genetic and epigenetic markers in GD patients. We will specifically discuss the association of genetic markers and epigenetic modifications with age of GD onset, severity of Graves' hyperthyroidism and the development of clinically evident Graves' orbitopathy.

Graves disease and Hashimoto disease form part of the spectrum of autoimmune thyroid disease (AITD), to which genetic and environmental factors are recognized contributors. Epigenetics provides a potential link between environmental influences, gene expression, and thyroid autoimmunity. DNA methylation (DNAm) is the best studied epigenetic process, and global hypomethylation of leukocyte DNA is reported in several autoimmune disorders. This review summarizes the current understanding of DNAm in AITD. Targeted DNAm studies of blood samples from AITD patients have reported differential DNAm in the promoter regions of several genes implicated in AITD, including TNF, IFNG, IL2RA, IL6, ICAM1, and PTPN22. In many cases, however, the findings await replication and are unsupported by functional studies to support causal roles in AITD pathogenesis. Furthermore, thyroid hormones affect DNAm, and in many studies confounding by reverse causation has not been considered. Recent studies have shown that DNAm patterns in candidate genes including ITGA6, PRKAA2, and DAPK1 differ between AITD patients from regions with different iodine status, providing a potential mechanism for associations between iodine and AITD. Research focus in the field is moving from candidate gene studies to an epigenome-wide approach. Genome-wide methylation studies of AITD patients have demonstrated multiple differentially methylated positions, including some in immunoregulatory genes such as NOTCH1, HLA-DRB1, TNF, and ICAM1. Large, epigenome-wide studies are required to elucidate the pathophysiological role of DNAm in AITD, with the potential to provide novel diagnostic and prognostic biomarkers as well as therapeutic targets.