UNASSIGNED: Micronutrients play pivotal roles in modulating various aspects of the immune response. However, the existing literature on the association between micronutrients and autoimmune thyroiditis (AIT) remains limited and contentious. To address this gap, we conducted Mendelian randomization (MR) to investigate potential links between genetically predicted concentrations of six micronutrients (Copper (Cu), Iron (Ir), Calcium (Ca), Vitamin D (VD), Vitamin C (VC), Zinc (Zn)) and the risk of AIT.
UNASSIGNED: Utilizing summary statistics from genome-wide association studies (GWAS) in individuals of European descent, we employed MR methodologies to elucidate the interplay between micronutrients and AIT. Three distinct MR techniques were employed: Inverse Variance Weighted (IVW), MR-Egger regression, and Weighted Median Estimator (WME). Additionally, we evaluated outcome heterogeneity using Cochran\'s Q statistic and assessed pleiotropy using the MR-Egger intercept.
UNASSIGNED: IVW analysis revealed no substantial evidence supporting a significant impact of genetically predicted micronutrient concentrations on AIT risk (Cu: OR = 0.918, P = 0.875; Ir: OR = 0.653, P = 0.264; Ca: OR = 0.964, P = 0.906; VD: OR = 0.717, P = 0.378; VC: OR = 0.986, P = 0.875; Zn: OR = 0.789, P = 0.539). Cochran\'s Q test for IVW indicated no notable heterogeneity. Moreover, the MR-Egger intercept method suggested the presence of horizontal pleiotropy between serum VC levels and AIT (MR-Egger intercept = -0.037, p = 0.026), while no such pleiotropy was observed for other micronutrients.
UNASSIGNED: Our MR analysis does not support a causal relationship between genetically predicted concentrations of six micronutrients (Cu, Ir, Ca, VD, VC, and Zn) and the risk of AIT.

Autoimmune thyroiditis (Hashimoto\'s thyroiditis) is the most common autoimmune disease. It most often manifests itself as hypothyroidism but may also present with euthyroidism or even hyperthyroidism. The etiopathogenesis of autoimmune thyroiditis is still unclear. However, in addition to genetic and epigenetic factors, many environmental factors are known to increase the risk of developing AIT. In this review, we aimed to collect and analyze data connected with environmental factors and autoimmune thyroiditis development. Our review indicates iodine intake, vitamin D deficiency, selenium deficiency, viral infections caused by Epstein-Barr Virus (EBV), Human parvovirus B19 (PVB19), Human herpesvirus 6A (HHV-6A) and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), bacterial infection caused by Helicobacter pylori, microbiome disruption, medications such as interferon-alpha and tyrosine kinase inhibitors, as well as stress, climate, and smoking can influence the risk of the occurrence of autoimmune thyroiditis. Having knowledge of risk factors allows for making changes to one\'s diet and lifestyle that will reduce the risk of developing the disease and alleviate the course of autoimmune thyroiditis.

Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field.

OBJECTIVE: Autoimmune thyroiditis (AIT) is the most common autoimmune thyroid disease. In recent decades, its incidence and prevalence have sharply increased. Yiqi Huatan Huoxue recipe is a traditional Chinese medicine formula we use to treat AIT. Its clinical efficacy is clear, but the specific mechanism remains unclear. This study aims to explore whether pyroptosis mediated by the SIRT1/NF-κB/NLRP3 signaling pathway is one of the therapeutic mechanisms of Yiqi Huatan Huoxue recipe.
METHODS: Forty 8-week-old female NOD.H-2h4 mice were randomly divided into four groups: the normal group (NG), model group (MG), Yiqi Huatan Huoxue recipe group (YG), and western medicine group (selenium yeast tablet, SeG). The normal group was gavaged with distilled water, while the remaining groups were gavaged with 0.05% sodium iodide (NaI) solution for 8 weeks. After the AIT animal model formed naturally, the mice were euthanized by gavage after 8 weeks. Hematoxylin-eosin staining was used to observe thyroid tissue changes, and enzymelinked immunosorbent assay (ELISA) was used to detect serum anti-thyroglobulin antibodies (TGAb) and mouse anti-thyroid peroxidase antibodies (TPOAb). Real-time quantitative PCR (qRT-PCR), Western blot, and immunohistochemistry were used to detect the expression of sirtuin 1 (SIRT1), nuclear factor κB p65 (NF-κB p65), nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase- 1, gasdermin D (GSDMD), and interleukin (IL)-1β in thyroid tissue.
RESULTS: Compared with the NG group, the thyroid structure of rats in the MG group was severely damaged, with significant lymphocyte infiltration, significantly increased serum TGAb and TPOAb levels, and significantly increased expression levels of SRIT1, NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD, IL-1β mRNA, and protein. Compared with the MG group, the thyroid structure damage and lymphocyte infiltration in rats of each treatment group were improved, and the serum TGAb, TPOAb, SRIT1, NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD, IL-1β mRNA, and protein expression levels were significantly reduced.
CONCLUSIONS: Yiqi Huatan Huoxue recipe can alleviate thyroid structural damage in AIT mice, and its mechanism may be related to the upregulation of SIRT1, NF-κB deacetylation, and inhibition of NLRP3-mediated pyroptosis.

Background Detection and quantification of anti-thyroid antibodies make it possible to confirm the diagnosis of thyroid dysfunction as well as its autoimmune origin and monitor thyroid damage in diabetic patients. The aim of this study is to determine the seroprevalence of anti-thyroid antibodies in hospitalized diabetic patients. Materials and methods This retrospective study focused on 91 diabetic patients hospitalized in the endocrinology department of Ibn Sina Hospital, Rabat, Morocco, between January 1 and December 31, 2022. The study population was divided into two groups: 19 patients with type 1 diabetes (13 females and six males, with an age range of 20-70 years) and 72 patients with type 2 diabetes (52 females and 20 males, with an age range of 40-71 years). Hemoglobin (HbA1c) levels were determined with high-performance liquid chromatography (Hb-HPLC) analyzer from blood samples collected in EDTA tubes, and anti-thyroid antibodies (anti-TPO and/or anti-TG) were measured by chemiluminescent microparticle immunoassays (CMIA) in human serum using the ALINITY analyzer. Results Among type 1 diabetic patients, 42.1% (n = 8) were positive for anti-TPO and anti-TG antibodies, while 31.5% (n = 6) were positive only for anti-TPO antibodies. Among type 2 diabetic patients, 15.2% (n = 11) were positive only for anti-TPO antibodies, while 20.8% (n = 15) were positive for anti-TPO and/or anti-TG antibodies. The prevalence of anti-thyroid antibodies was higher in females, consistent with other studies. This could be linked to the involvement of autoimmune processes in the development of thyroid dysfunction in type 2 diabetics. Conclusions Testing for anti-thyroid antibodies in diabetic patients and their relatives helps detect subclinical conditions, which could later manifest as biological and clinical deficiencies, guiding monitoring parameters.

BACKGROUND: The T-cell receptor (TCR)/CD3 complex plays a crucial role in T-cell development and immune regulation. CD3G gene encodes one of the CD3 subunits named CD3γ, and its deficiency can cause autoimmune disorders, immunodeficiency and recurrent infections. To date, only 13 patients with CD3G variants have been reported.
METHODS: We report a 10-year-old Chinese boy presented with lupus-like disease in addition to autoimmune thyroiditis, asthma, immunodeficiency and recurrent infection. Flow cytometric analysis revealed apparently decreased levels of CD3+ and CD8+ T cells but mildly decreased CD4+ T cells. However, the activation of T cells and B cells increased.
RESULTS: Trio-based whole-exome sequencing revealed a homozygous pathogenic variant (c.213delA, p.Lys71fs) of CD3G gene in the proband. His parents were both heterozygous carriers of this variant.
CONCLUSIONS: This is the first patient who met the diagnostic criteria for systemic lupus erythematosus by the Systemic Lupus International Collaborating Clinics (SLICC) group. In addition to low T cells and low Treg cells, our study further revealed T cells and B cells activation enhanced in CD3γ deficiency patient, which may play an important role in autoimmunity. We believe that our study makes a significant contribution to the literature and will provide further insight into CD3γ deficiency and monogenic lupus.

UNASSIGNED: Pseudo-orthostatic tremor is a hyperkinetic movement disorder usually associated with other neurological comorbidities, mainly Parkinson\'s disease.
UNASSIGNED: A 65-year-old male presented with unsteadiness and leg tremor while standing. Electrophysiological evaluation confirmed the presence of pseudo-orthostatic tremor. Blood test showed an undiagnosed Graves\' disease. A complete remission of tremor was achieved with methimazole. Dopamine transporter scintigraphy showed a mild reduction of the striatal binding, bilaterally.
UNASSIGNED: Graves\' disease can be associated with pseudo-orthostatic tremor. Thyroid function should be assessed in patients complaining of unsteadiness. The causative role of hyperthyroidism in determining dopaminergic degeneration and uncovering subclinical parkinsonism warrants further investigations.

UNASSIGNED: We aimed to comprehensively investigate the causal relationship between 731 immune cell traits and autoimmune thyroiditis (AIT) and to identify and quantify the role of 1400 metabolic traits as potential mediators in between.
UNASSIGNED: Using summary-level data from genome-wide association studies (GWAS) we performed a two-sample bidirectional Mendelian randomization (MR) analysis of genetically predicted AIT and 731 immune cell traits. Furthermore, we used a two-step MR analysis to quantify the proportion of the total effects (that the immune cells exerted on the risk of AIT) mediated by potential metabolites.
UNASSIGNED: We identified 24 immune cell traits (with odds ratio (OR) ranging from 1.3166 6 to 0.6323) and 10 metabolic traits (with OR ranging from 1.7954 to 0.6158) to be causally associated with AIT, respectively. Five immune cell traits (including CD38 on IgD+ CD24-, CD28 on CD28+ CD45RA+ CD8br, HLA DR+ CD4+ AC, TD CD4+ %CD4+, and CD8 on EM CD8br) were found to be associated with the risk of AIT, which were partially mediated by metabolites (including glycolithocholate sulfate, 5alpha-androstan-3alpha,17beta-diol disulfate, arachidonoylcholine, X-15486, and kynurenine). The proportion of genetically predicted AIT mediated by the identified metabolites could range from 5.58% to 17.7%.
UNASSIGNED: Our study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.

BACKGROUND: Schmidt\'s syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison\'s disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign.
METHODS: A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies.
CONCLUSIONS: aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3].

BACKGROUND: Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated.
METHODS: An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis.
RESULTS: Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells\' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function.
CONCLUSIONS: Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.