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Abstract Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.

While subclinical or overt hypothyroidism are common in Down syndrome (DS); Graves’ disease (GD) is rare (ranges 0.6–3%). We aimed to evaluate the clinical features, course, and treatment of GD in children with DS and compare them with those without DS. Among 161 children with GD, 13 (8 female, 5 male) had DS (8%). Data were collected retrospectively from patients’ medical records. The mean age at diagnosis was 10.6 ± 4.5 years, with a female-to-male ratio 1.6:1. The main symptoms were weight loss (n = 6), increased irritability (n = 3), and increased sweating (n = 3). None had orbitopathy. Seven of 11 patients with a thyroid ultrasound at diagnosis had a goitre. On admission, all had thyroid-stimulating hormone (TSH)

Diseases of the thyroid gland occupy one of the central places in clinical endocrinology. The main components for the synthesis of thyroid hormones are iodine and the amino acid tyrosine. Studies conducted in the 21st century indicate a certain effect on the metabolism and function of the thyroid gland and other microelements and vitamins. We searched the PubMed and Scopus information databases for publications devoted to the study of the influence of trace elements selenium, zinc, vitamins A, C, E on the physiology and pathology of the thyroid gland, including sources up to 29.02.2024. Adequate intake of selenium, zinc, along with two other important microelements (iodine and iron), as well as vitamins A, C, E, contributes to normal metabolism of the thyroid gland. Maintaining a physiological balance of micronutrients and vitamins through a sensible diet or taking nutraceuticals is essential to preventing thyroid disease and maintaining overall health. Basal analysis of microelements and vitamins seems appropriate for better selection of patients in need of replacement therapy using nutraceuticals

Abstract Background Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. Methods Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations. Results At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex. Conclusions This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.

Abstract Background Autoimmune hepatitis (AIH) is an organ specific autoimmune disease, which can manifest at any age of life. there is a high prevalence of extrahepatic autoimmune diseases in patients with AIH. Autoimmune thyroid diseases (ATDs) are the most frequent extrahepatic autoimmune disorders among patients with AIH. Aim of work is to detect the frequency of ATDs among Egyptian children with AIH. Methods This research is a cross-sectional study conducted on 58 children with AIH aged ≤ 18 years. All patients were tested for free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG). Thyroid ultrasound (US) and thyroid scan were performed for patients with abnormal thyroid profile, borderline values, positive anti-TPO or anti-TG. Results The mean ± standard deviation (SD) for the age of the patients was 11.3 ± 4.5 years. Out of 58 patients of AIH, 28 patients (48.3%) had associated other autoimmune diseases. Autoimmune thyroiditis was the most common associated autoimmune disease being present in 10 patients (17.2%). The thyroid status of AIT patients showed that 6 patients (60%) were euthyroid, 3 patients (30%) had subclinical hypothyroidism and only one patient (10%) was hyperthyroid. Conclusion Autoimmune hepatitis in Egyptian children is commonly associated with other autoimmune diseases. Autoimmune thyroiditis is the most common to be associated with AIH in pediatric patients. As it is not usually clinically manifesting, regular screening for AIT in children with AIH is mandatory.

The aim of the study was to examine the involvement of tissue-specific and non-specific autoantibodies, matrix metalloproteinase-3 and neuron-specific enolase (NSE) enzymes in the development and exacerbation of autoimmune thyroiditis. Materials and methods. The study enrolled 170 patients with autoimmune thyroiditis (64 males and 106 females aged 18 to 64 years) to comprehensively examine their humoral immune response indicators (IgA, M, G), organ-specific (Ab-TG, Ab-TPO) and organ-non-specific antibodies (Ab-DNA), metalloproteinase-3 and NSE activity. The control group consisted of 65 individuals without thyroid pathologies or other autoimmune diseases, aged 20 to 65 years (26 males and 39 females). Results. The study has demonstrated changes in the levels of organ-specific and organ-nonspecific antibodies and statistically significantly increased metalloproteinase-3 activity in patients with autoimmune thyroiditis. Positive correlations have been found between elevated levels of IgG, Ab-TG, Ab-TPO, Ab-dsDNA and NSE activity. Negative correlations have been observed between NSE activity and IgA concentrations. Conclusions. Elevated titers of anti-DNA autoantibodies may indicate an aggravation of the autoimmune process due to cellular structure damage, resulting in gland dysfunction. The findings also suggest that metalloproteinase-3, a marker predicting thyroid tissue damage, may negatively impact the immune response induction, ultimately affecting the activity of neuron-specific enolase. The data have shown that studying biochemical indicators such as antinuclear antibodies (ANA), anti-DNA antibodies, metalloproteinase-3 and neurodegenerative indicators could provide informative markers to determine the nature of the disease development and worsening.

ObjectiveNumerous observational and retrospective studies have demonstrated an association between Autoimmune Thyroiditis (AIT) and various systemic Autoimmune Diseases (AIDs). However, the causal relationship between them remains uncertain. This study aims to investigate the causal link between AIT and diverse types of AIDs utilizing the Mendelian Randomization (MR) method.MethodWe assessed the causal relationship between AIT and eight prevalent AIDs. Summary statistics from genome-wide association studies (GWAS) were sourced from the FinnGen biobank and IEU Open GWAS database. Two-sample MR analyses were conducted, with the primary statistical approach being the Inverse Variance Weighting (IVW) method. This was complemented by a series of sensitivity analyses, and the robustness of the findings was evaluated through the estimation of heterogeneity and pleiotropy.ResultsWhen AIT was considered as the outcome, MR evidence suggested an association between Rheumatoid arthritis (RA), Type 1 diabetes (T1D), and Systemic lupus erythematosus (SLE) with AIT. Utilizing the Inverse Variance Weighting (IVW) method, we observed an increased risk of AIT with exposure to RA (P = 0.024, OR=1.25; 95% CI = 1.03, 1.52), T1D (P < 0.001, OR=1.27 95% CI = 1.11,1.46), and SLE (P = 0.037, OR=1.14; 95% CI = 1.04,1.26). Conversely, no significant genetic causal relationship with AIT was found for Sjögren’s syndrome (SS), Ankylosing Spondylitis (AS), Multiple sclerosis (MS), Crohn’s disease (CD), and Ulcerative colitis (UC).ConclusionThis study identified RA, T1D, and SLE as triggering factors for AIT. The incidence rate of AIT in patients with RA, T1D, and SLE may be higher than that in the general population. Therefore, individuals with these three diseases should undergo regular monitoring of thyroid-related indicators.

BackgroundMicronutrients 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.MethodUtilizing 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.ResultIVW 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.ConclusionOur 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.

Introduction and aim of the study: The growing awareness of gluten-related disorders has led to widespread misinformation about the gluten-free diet(GFD). The potential benefits of removing gluten are not well evaluated, yet it is often recommended or self-implemented by patients without robust supporting evidence. This paper aims to determine whether eliminating gluten from the diet provides proven benefits for individuals with specific diseases, including autoimmune thyroiditis (AIT), type 1 diabetes (T1D), psoriasis, and metabolic syndrome, who do not have a diagnosed gluten-related disorder. Description of the state of knowledge: Adhering to a gluten-free diet may benefit patients with AIT and T1D even without celiac disease, although there is no clear evidence that it alleviates AIT or T1D symptoms and the improvements are not significant enough to recommend it universally. Further research on humans is needed to explore the potential preventive effect of GFD on T1D risk and prolonging partial remission. For psoriasis, a GFD can be beneficial for patients with gluten-related antibodies, potentially reducing or clearing skin lesions, but it shows no benefit for those without these antibodies. The data on the GFD's impact on cardiovascular disease remains contradictory and unreliable. Conclusion: For psoriasis patients who test positive for gluten-related antibodies, a gluten-free diet can be recommended. Current studies do not substantiate the necessity for patients with AIT, T1D or metabolic syndrome to completely eliminate gluten from their diet.

IntroductionWe 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.MethodsUsing 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.ResultsWe 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%.DiscussionOur study identified causal associations between AIT and immune cells which were partially mediated by metabolites, thus providing guidance for future clinical and basic research.

Objectives. To assess autoimmune thyroiditis prevalence in subclinical and clinical psoriatic arthritis (PsA). Materials and methods. 45 female adult Egyptian patients with psoriatic disease were classified into 3 equal groups: PsA, subclinical PsA, and psoriasis. A full assessment was done including Health Assessment Questionnaire, Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), PsA disease activity score (DAPSA), MAdrid Sonographic Enthesitis Index (MASEI), thyroid hormones (TSH, FT4, and FT3), thyroglobulin and thyroid peroxidase antibodies (Tg and TPO Abs), and thyroid ultrasound. Results. Thyroid abnormalities prevalence was: 33.3% with subclinical hypothyroidism, 80% with positive TPO Ab, and 46.7% with positive Tg Ab in PsA group, 26.7% with subclinical hypothyroidism, 60% with positive TPO Ab, and 33.3% with positive Tg Ab in subclinical PsA group and none in psoriasis group. PsA patients had higher TPO Ab levels compared to psoriasis patients with high statistical significant difference and lower FT3 levels compared to psoriasis patients with statistical significant difference. In subclinical PsA group, MASEI was positively correlated with TPO Ab with high statistical significance and with FT3 and Tg Ab with statistical significance, FT4 was negatively correlated with LEI with high statistical significance, and FT4 was correlated with PASI with statistical significance. In PsA group, TPO Ab was correlated with DAPSA with statistical significance. Conclusions. Autoimmune thyroiditis is more common in PsA than subclinical PsA patients. PsA patients are advised to be tested for TPO and Tg Abs. Musculoskeletal ultrasound is a screening tool to detect enthesitis in psoriasis patients.

Purpose: We investigated whether selenium supplementation improves quality-of-life (QoL) in patients with autoimmune thyroiditis (ID:NCT02013479). Methods: We included 412 patients ≥18 years with serum thyroid peroxidase antibody (TPOAb) level ≥100 IU/mL in a multicentre double-blinded randomised clinical trial. The patients were allocated 1:1 to daily supplementation with either 200 μg selenium as selenium-enriched yeast or matching placebo tablets for 12 months, as add-on to levothyroxine (LT4) treatment. QoL, assessed by the Thyroid-related Patient-Reported-Outcome questionnaire (ThyPRO-39), was measured at baseline, after 6 weeks, and after 3, 6, 12, and 18 months. Results: In total, 332 patients (81%) completed the intervention period, of whom 82% were women. Although QoL improved during the trial, no difference in any of the ThyPRO-39 scales was found between the selenium group and the placebo group after 12 months of intervention. In addition, employing linear mixed model regression no difference between the two groups was observed in the ThyPRO-39 composite score (28.8 (95% CI: 24.5–33.6) and 28.0 (24.5–33.1), respectively; P = 0.602). Stratifying the patients according to duration of the disease at inclusion, ThyPRO-39 composite score, TPOAb level, or selenium status at baseline did not significantly change the results. TPOAb levels after 12 months of intervention were lower in the selenium group than in the placebo group (1995 (95% CI: 1512–2512) vs 2344 kIU/L (1862–2951); P = 0.016) but did not influence LT4 dosage or free triiodothyronine–free thyroxine ratio. Conclusion: In hypothyroid patients on LT4 therapy due to autoimmune thyroiditis, daily supplementation with 200 μg selenium or placebo for 12 months improved QoL to the same extent.

Jiawei Lu,1 Lebin Song,1 Jiaochen Luan,2 Yifei Feng,1 Yidan Wang,1 Xuechen Cao,1 Yan Lu1 1Department of Dermatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yan Lu, Department of Dermatology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86 13913967126, Email luyan6289@163.comBackground: Vitiligo and Hashimoto’s thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers.Methods: We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR).Results: Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity.Conclusion: IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.Keywords: depigmenting skin disorder, autoimmune thyroiditis, immune cell infiltration, bioinformatics analysis

Background: Sclerosing mucoepidermoid carcinoma of the thyroid gland was first reported in 1991. This type of a tumor may develop in connection with Hashimoto's thyroiditis. There are two variants of mucoepidermoid carcinoma of the thyroid gland: the normal and sclerosing types. Sclerosing mucoepidermoid carcinoma of the thyroid gland has recently been recognized by the World Health Organization as a separate disease. Сlinical case description: We present a clinical case of a 51-year-old woman who was observed for 2 years for autoimmune thyroiditis with nodulation. The patient had no symptoms or signs of compression. The level of thyroid–stimulating hormone was 15.8 (range 0.4–4.0), the level of antibodies to peroxidase was 150 IU/ml. Thyroid scintigraphy revealed a dominant cold node (1.5×2 cm) in the right lobe of the gland. During the control ultrasound examination of the neck, negative dynamics was observed, then a fine needle aspiration biopsy of the thyroid node was performed. A follicular tumor was found against the background of Hashimoto's thyroiditis, which was the reason for a timely treatment. In the described case, the patient underwent a total thyroidectomy without neck lymph node dissection, no postoperative radiotherapy or other auxiliary treatments were performed. A full-body scintigraphy showed no recurrence of the disease in 10 months after the initial treatment. Conclusion: Given the rarity of the disease and the impossibility to differentiate it from other thyroid tumor’s, a more thorough examination of the nearby lymphatic collectors is necessary to exclude metastatic lesions, and in the presence of altered lymph nodes, additional diagnosis by fine-needle aspiration biopsy with subsequent determination of the scope of surgical treatment and postoperative management of this category of patients is indicated.

AbstractAutoimmune thyroiditis (AIT), also known as Hashimoto’s thyroiditis (HT), is an autoimmune disease that is characterised by elevated thyroid-specific antibody titres. The incidence of AIT is increasing year over year, making it urgent to establish a suitable animal model for this condition, in order to better explore its pathogenesis and potential pharmaceutical mechanisms for treatment. Owing to a lack of basic research on this disease, problems such as disparate modelling methods with unclear and varying success rates make it difficult for researchers to obtain effective information on AIT in the short term. This report summarises and analyzes the current literature on AIT and combines actual operability to explain the selection and specific implementation processes behind the uses of different modelling approaches, to provide a better overall understanding of autoimmune thyroid diseases.

Background Autoimmune thyroiditis is closely associated with major depressive disorder (MDD) and suicide attempts. However, few studies have examined this relationship. Aims The study aimed to assess the prevalence and correlates of suicide attempts in patients with first-episode drug-naïve (FEDN) MDD and autoimmune thyroiditis. Method We recruited 1718 out-patients with FEDN MDD and assessed depressive, anxiety and psychotic symptoms with the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety (HRSA) and Positive and Negative Syndrome Subscale positive subscale, respectively. The serum levels of free triiodothyronine, free thyroxine, thyroid stimulating hormone (TSH), antithyroglobulin, thyroid peroxidase antibody (TPOAb) and several other metabolic parameters were assessed. Patients were divided into non-autoimmune thyroiditis, autoimmune thyroiditis only and autoimmune thyroiditis with abnormal TSH groups, based on autoimmune thyroiditis severity. Multiple logistic regression model was applied to identify the correlates of suicide attempts in patients with MDD and autoimmune thyroiditis with abnormal TSH. Results Compared with the non-autoimmune thyroiditis group, the autoimmune thyroiditis with abnormal TSH group had a nearly fourfold higher likelihood of reporting a suicide attempt, whereas no difference was found between the non-autoimmune thyroiditis and autoimmune thyroiditis only groups. HRSA score, lnTPOAb and lnTSH were independently associated with suicide attempts in patients with autoimmune thyroiditis with abnormal TSH. Conclusions Patients with MDD and autoimmune thyroiditis with abnormal TSH are at higher risk for suicide attempt. TPOAb, TSH and anxiety are all independently associated with suicide attempts in this population, and regular thyroid checks are warranted.

In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7–2 μg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels.

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disorder characterized by an immune response targeting the thyroid gland. Genetic factors play a significant role in AIT susceptibility, with immune-related genes, especially the vitamin D receptor (VDR) gene, potentially influencing AIT development. This comprehensive review delves into the intricate association between VDR gene polymorphisms, particularly rs2228570 (FokI), and AIT susceptibility, exploring various populations. Research has unveiled contrasting outcomes regarding the link between the VDR rs2228570 polymorphism and AIT risk across diverse ethnic groups. Certain populations have exhibited a noteworthy correlation, suggesting that population-specific genetic factors contribute to AIT risk. A recurring observation of vitamin D deficiency in AIT patients has correlated with elevated anti-thyroid antibodies, abnormal thyroid function, and thyroid volume. The results emphasize the possible role of vitamin D in the development of AIT, suggesting the importance of vitamin D supplementation to address deficiencies associated with AIT. In addition to VDR rs2228570, other genetic variants have also shown associations with AIT susceptibility, displaying varying results across different populations. Ethnicity emerges as a pivotal factor influencing these associations, underscoring the need to consider genetic variations in diverse populations. We emphasize the intricate interplay between VDR gene polymorphisms, vitamin D, and AIT susceptibility. Extensive research is essential to unveil the clinical significance of these genetic variations, offering prospects for enhanced diagnostic and therapeutic strategies for individuals with AIT.

INTRODUCTION: The aim of this study was to compare the development of early diabetic retinopathy (DR) findings, a microvascular complication, between patients with isolated type 1 diabetes mellitus (T1DM) (Group 1), concurrent T1DM and autoimmune thyroiditis (AT) (Group 2), and healthy controls (Group 3), who were matched for age, sex, number, and body mass index for comparison. METHODS: This was a prospective observational study that included individuals aged 10-20 years, and patients in Groups 1 and 2 had been followed up for ≥5 years. None of them developed clinical DR during the follow-up period. Optical coherence tomography angiography (OCTA) was used to evaluate the foveal avascular zone (FAZ) and parafoveal vascular density (PVD) for the development of early DR. OCTA findings were compared between patients and healthy controls. RESULTS: Thirty-five individuals were included in each of the groups. The mean FAZ and PVD differed significantly between the three groups (FAZ, p=0.016; PVD, p=0.006). The mean FAZ was higher in Groups 1 and 2 than in Group 3 (p=0.013 and p=0.119, respectively). The mean PVD was lower in Groups 1 and 2 than in Group 3 (p=0.007, respectively). No significant difference was found between Groups 1 and 2 in terms of the mean FAZ and PVD (p=0.832 and p=0.653, respectively). The mean glycated hemoglobin (HbA1c) level was significantly correlated with FAZ and PVD (FAZ: r=0.496, p

Autoimmune polyglandular syndromes (APS) are a heterogeneous group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of central or peripheral immune tolerance. These syndromes are also often accompanied by autoimmune damage to non-endocrine organs. Taking into account the wide range of components and variants of the disease, APS is usually divided into a rare juvenile type (APS 1) and a more common adult type (APS 2–4). APS type 1 is caused by a monogenic mutation, while APS types 2–4 have a polygenic mode of inheritance. One subtype of adult APS (APS 3D) is characterized by a combination of autoimmune thyroid disease and autoimmune rheumatic disease. This review considers the available literature data on combinations that meet the above criteria. Many studies have noted a significantly higher prevalence of rheumatic diseases in patients with autoimmune thyroid disease compared with the control group. Also, as in a number of rheumatic diseases, a more frequent occurrence of autoimmune thyroiditis, primary hypothyroidism and Graves' disease was noted.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been linked to disease severity, it could be considered an optimal early biomarker to identify therapeutic approach efficacy. In conclusion, by gaining insights into how these molecules function and which cells they interact with, future studies can devise targeted therapies to address various neurological, immunological, and other disorders more effectively. This knowledge may pave the way for innovative treatments based on NGF manipulation aimed at improving the quality of life for individuals affected by diseases involving neurotrophins.

Background/Objective: Our objective is to highlight the importance of identifying symptoms of steroid-responsive encephalopathy with associated thyroiditis (SREAT), especially in the setting of intermittent cognitive dysfunction, and to inform that SREAT can develop even in patients with a history of partial thyroidectomies. Case Report: We present a case of a 51-year-old woman with a long-standing history of hypothyroidism presenting with acute onset myoclonus, involuntary tremors, fatigue, malaise, and palpitations for two weeks, with intermittent lapses in cognitive function. The patient’s workup is completely within normal limits, including her cognition, except for elevated thyroid stimulating hormone levels and markedly elevated levels of antithyroid peroxidase antibodies, despite the fact that she previously had a partial thyroidectomy. Discussion: SREAT is an autoimmune condition characterized by cognitive dysfunction, elevated thyroid autoantibodies, and therapeutic response to corticosteroids. SREAT is primarily considered a diagnosis of exclusion. A crucial feature is the hallmark of significant improvement in symptoms when glucocorticoids are administered. There is a significant correlation between patients with elevated antithyroid peroxidase antibodies and new-onset SREAT. Although total thyroidectomy has been reported as a definitive treatment of SREAT, response to corticosteroids is the “sine qua non” in diagnosing this condition. Conclusion: Hashimoto's thyroiditis can lead to a rare complication called SREAT, presenting with various neurologic symptoms. Prompt glucocorticoid treatment is vital, and a positive response confirms the diagnosis. Total thyroidectomy may be necessary for definitive SREAT treatment. More research is needed for alternate treatments and an understanding of the pathophysiology of SREAT.

Abstract Background Recent studies have reported associations between body mass index (BMI) and various autoimmune disorders. However, it is still uncertain whether there exists a direct cause-and-effect relationship between BMI and autoimmune thyroiditis (AIT). The aim of our study is to investigate the causal association between BMI and AIT. Methods We conducted a two-sample summary data Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary statistics data related to BMI as exposure, and GWAS summary statistic data sets for AIT as the outcome. Robustly associated single-nucleotide polymorphisms (SNPs) for BMI were selected as instrumental variables (IVs). We used the inverse variance weighted (IVW) method as the primary method and performed other MR methods such as MR-Egger regression, weighted median, simple mode, and weighted mode analyses for further validation. The slope of MR-Egger regression was used to correct for pleiotropy and provide estimates of causality. The p-value for the intercept in MR-Egger was utilized to detect any directional pleiotropic effects. Heterogeneity and sensitivity analyses were performed to assess the robustness of our findings. Results Seventy-eight SNPs were selected from GWAS on BMI as the IVs. Our MR analysis using the IVW method showed a potential causal association between BMI and AIT (OR = 3.071, 95% CI 1.324–7.118). Findings from other MR methods are non-significant, although the direction of effect is consistent. There was no evidence that the result was affected by genetic pleiotropy (MR-Egger regression intercept = 0.01, SE = 0.00025, p = 0.719). Heterogeneity and sensitivity analyses revealed no significant heterogeneity among SNPs, and no single SNP drove the observed associations. Conclusion Our findings suggest a potential causal association between BMI and AIT, which may provide a basis for further investigation into the relationship between BMI and AIT. Further studies are required as only the IVW method shows significant results, and the case sample size is small.

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.

Selenium (Se) is an essential trace element of fundamental importance for human health. Se is incorporated into selenoproteins (SPs) which are endowed with pleiotropic effects including antioxidant and anti-inflammatory effects and active production of thyroid hormones. It has also been suggested that Se plays a crucial role in the pathogenesis of various human diseases. The therapeutic effects of supplementation with Se have already been described in various thyroid diseases. However, there are still conflicting results regarding the optimal dose of Se to administer and the duration of treatment, efficacy, and safety. The highly beneficial effects of supplementation with Se have been observed in subjects with thyroid disease in the hyperthyroid phase. In line with these observations, clinical studies have shown that in patients with Basedow's disease (BD) and autoimmune thyroiditis (AT), treatment with a combination of antithyroid drugs and Se restores the euthyroid state faster than administration of antithyroid drugs alone. However, the efficacy of this therapeutic approach remains to be better evaluated.

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.

IntroductionHashimoto’s thyroiditis (HT) is nowadays the leading cause of hypothyroidism with high and still growing prevalence in general population, but there are lack of data regarding migraine and HT connection.MethodsThe aim of this study was to analyze the prevalence of HT in migraine and to check if the presence of HT influence migraine severity. This retrospective observational cohort study involved consecutive migraine patients consulted at our Headache Center with diagnosis of migraine. Electronic charts of patients were collected, including data on migraine type, presence of cranial autonomic symptoms (CAS), monthly migraine days (MMD), medication overuse headache (MOH), and the presence of comorbidities including HT.ResultsWe found 928 eligible migraine patients, 88.7% were women. The mean age was 36.09 years. 592 (63.8%) were diagnosed with episodic migraine (EM), the rest with chronic migraine (CM). MOH was additionally diagnosed in 258 (27.8%) patients. The duration of migraine was 15.99 years. 106 (11.4%) was diagnosed with HT, 148 (15.9%) with hypothyroidisms, while 84 (9.05%) had both diagnosis. Migraine patients with HT were significantly older (p

Background: Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high prevalence, the pathogenesis of AIT remains unclear. Previous studies have suggested a potential association between gut microbiota and AIT. However, whether this relationship is causal or coincidental remains uncertain. To address this gap in knowledge, our study aimed to investigate the potential causal association between gut microbiota and AIT using the two-sample Mendelian randomization (MR) method. Methods: Summary-level gut microbiota data comprising 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) were obtained from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were extracted from the UK Biobank, FinnGen study, and various extensive GWAS studies. A meticulous MR analysis was conducted to evaluate the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. Sensitivity analyses and tests for heterogeneity were systematically performed to validate the reliability of our findings. Results: Six gut microbiota species showed significant associations with AIT according to the IVW method. Among them, the following exhibited negative associations with AIT: family Alcaligenaceae, family Pasteurellaceae (ID: 3689), family Peptococcaceae, genus Lachnospira, genus Victivallis, and order Pasteurellales (ID: 3688). No evidence of pleiotropy or heterogeneity was detected. Conclusion: The MR analysis uncovered a causal relationship at the genetic prediction level between specific gut microbiota and AIT. These findings offer novel insights into the mechanisms governing the development of AIT mediated by gut microbiota. This knowledge could inform the design of future interventions, potentially involving microbiome-related strategies, to address the mechanisms associated with AIT development.

BackgroundSARS-CoV-2 could trigger multiple immune responses, leading to several autoimmune diseases, including thyroid diseases. Many cases of thyroid diseases caused by COVID-19 infection have been reported. Here, we describe the disease development of patients with autoimmune thyroid disease after COVID-19 infection.MethodsThe clinical characteristics, diagnosis and treatment of five different patients with autoimmune thyroid disease after COVID-19 infection were reported.ResultsFemale patients with primary autoimmune thyroid disease which have been stable for many years were reported. One month after COVID-19 infection, the disease has undergone different evolution. Case 1, a patient with history of long-term stable Hashimoto’s thyroiditis, suddenly suffered from Graves disease after COVID-19 infection. Case 2, a patient with history of long-term stable Hashimoto’s thyroiditis with thyroid nodules, suddenly suffered from Graves disease after infection. Case 3, a patient with history of long-term stable Graves disease, suddenly suffered from worsening after infection. The above three cases showed thyroid-stimulating antibodies were enhanced. Case 4, a patient with history of previous hypothyroidism had an increase in thyroid-related antibody (TPOAb and TRAb) activity after infection, followed by a marked worsening of hypothyroidism. Case 5, a patient with no history of thyroid disease suddenly developed controllable “thyrotoxicosis” after infection, suggesting the diagnosis of painless thyroiditis.ConclusionThe five case reports show a different development of the primary autoimmune thyroid disease after COVID-19 infection. The change in the trend of thyroid disease is closely related to the immune response induced by SARS-CoV-2 infection.

ObjectiveThe influence of vitamin D on autoimmune thyroid disease (AITD) remains a subject of ongoing debate. This study employs Mendelian randomization (MR) to investigate the causal correlations of serum 25-hydroxyvitamin D (25[OH]D) levels with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves disease (GD).MethodsData on single nucleotide polymorphisms related to serum 25(OH)D levels, AIT, AIH, and GD were sourced from UK Biobank and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were employed to test the exposure-outcome causal relationship. Assessments of horizontal pleiotropy, heterogeneity, and stability were performed using the MR-Egger intercept, Cochran’s Q test, and leave-one-out sensitivity analysis, respectively.ResultsThe results of MR analysis showed increased serum 25(OH)D levels was associated with a reduced risk of AIT (OR 0.499, 95% CI 0.289 to 0.860, p = 0.012) but not causal associated with AIH (OR 0.935, 95% CI 0.695 to 1.256, p = 0.654) and GD (OR 0.813, 95% CI 0.635 to 1.040, p = 0.100). Intercept analysis showed no horizontal pleiotropy (p > 0.05), and Cochran’s Q test showed no heterogeneity (p > 0.05). Sensitivity analysis suggested that these results were robust.ConclusionAn increased serum 25(OH)D level is associated with AIT risk reduction but unrelated to AIH and GD. This finding suggests that vitamin D supplementation can be valuable for preventing and treating AIT.

BackgroundBibliometrics has been used to analyze the literature in the field of thyroid disease studies in the early 21st century, indicating the changes in current international study trends.MethodsIn this study, a bibliometric analysis of data retrieved from the Web of Science (WoS) database was conducted, and the publication trends and thematic evolution in the field of thyroid disease research from January 1, 2000, to November 16, 2022, were analyzed. A total of 69283 articles related to thyroid diseases were evaluated for their characteristics, including annual publication volume, countries, journals, institutions, authors, keywords, and references. VOSviewer was utilized to perform the analysis of co-authorship, co-citation, co-occurrence and descriptive.ResultsThe annual publication volume of thyroid disease research literature showed a fluctuating upward trend from 2000 to 2021, exceeding 5,000 articles for the first time in 2021. The United States (16120 counts, 678255 cities) ranks first in terms of publication volume and citation. Thyroid (n=3201) and Journal of Clinical Endocrinology&Metabolism (n=140399) are the most prolific and cited journals, respectively. The organization with the highest publication volume and citation frequency is Harvard University (1011 counts, 59429 cities), Miyauchi Akira (n=422), Schlumberger, and Martin (n=24839) possess the highest publication volume and citation frequency, respectively. Co-occurrence analysis of 307 keywords with frequencies of more than 20 resulted in 6 clusters (1): Thyroid dysfunction and diseases (2); mechanism of occurrence and development of thyroid cancer (3); autoimmune thyroiditis (4); scope and postoperative management of thyroid surgery (5); fine needle aspiration of thyroid nodules (6); radioactive iodine therapy for thyroid cancer. Active monitoring, thermal ablation, Lenvatinib, and long noncoding RNA refer to the latest keywords. Discussing the six clusters helps scholars to determine the scope and direction of studies.ConclusionOver the past two decades, the literature related to thyroid diseases has increased year by year, with closer collaboration between countries, institutions, and authors. In this study, the global trends, research hotspots, emerging subjects, and basic knowledge of literature related to thyroid diseases were respectively elucidated, which will facilitate researchers in this field to seek better development.

Abstract Purpose We investigated the association between health-related quality of life (HRQL) and the severity of hypothyroidism at diagnosis in patients referred to a secondary hospital clinic. Methods Sixty-seven adult patients referred from primary care were enrolled. All patients had newly diagnosed hypothyroidism due to autoimmune thyroiditis and were treated with levothyroxine (LT4). The dose was adjusted according to thyroid function tests aiming at a normal plasma thyrotropin. Patients were stratified according to the severity of hypothyroidism in two different ways: the conventional approach (subclinical or overt hypothyroidism) and a novel approach according to the change (decrease or increase) in plasma level of free triiodothyronine index (FT3I) following LT4 treatment. The ThyPRO-39 questionnaire was used for measurement of HRQL at referral to the Endocrine Outpatient Clinic (higher score corresponds to worse HRQL). Results Free thyroxine index (FT4I) at diagnosis correlated positively with the scores on the Hypothyroid Symptoms and Tiredness scales (p = 0.018 for both). In accordance, patients with subclinical hypothyroidism (n = 36) scored higher on Hypothyroid Symptoms (p = 0.029) than patients with overt hypothyroidism (n = 31). The difference in HRQL was more pronounced if patients were stratified according to the dynamics in FT3I following LT4 treatment. Thus, patients who showed a decrease in FT3I following treatment (n = 24) scored significantly worse for Anxiety (p = 0.032) and Emotional Susceptibility (p = 0.035) than patients with an increase in FT3I (n = 43). Conclusion Patients referred to an endocrine clinic with mild hypothyroidism had an impaired HRQL, compared to patients with more severe hypothyroidism. The most likely explanation of this finding is a lower threshold for seeking medical consultation and secondary care referral if HRQL is deteriorated. The dynamics in plasma FT3I following treatment may be more sensitive for such a discrimination in HRQL than a stratification according to the thyroid function tests at diagnosis.

Introduction:Although more common in adults, autoimmune thyroiditis (AT) is one of the most common thyroid diseases in children and adolescents. Salivary gland involvement has been described in many studies of patients with AT. Several inflammatory scores are used to assess the inflammatory status of patients with systemic autoimmune diseases. We aimed to sonographically evaluate the parotid and submandibular salivary glands with inflammatory parameters in patients with AT in our study.Methods:Our study population consisted of 37 consecutive pediatric AT patients and 29 healthy control subjects. Ultrasonographic and laboratory evaluations of the study population were performed. Jamovi and MedCalc software were used to analyze the data.Results:The volume of the thyroid gland in the patients was significantly higher than that in the control group (p=0.030), while there was no difference in the volume of the salivary glands. Multiple logistic regression analysis was planned to assess the predictability of salivary gland involvement in patients with the disease. Both systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV) were found to be predictors of salivary gland involvement in AT patients.Conclusion:We found that both SII and PIV inflammatory markers are predictive of salivary gland parenchymal changes in patients with AT, and SII is likely to be more valuable than PIV at this time.

Objective: A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditi s (AIT). Methods: Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyr oid tissues, and its association with serum and tissue inflammatory biomarkers were a ssessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to i nvestigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturb ance on EAT. Results: The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS le d to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups. Conclusions: This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular cir cadian rhythm can alleviate autoimmune thyroid diseases warrants further research.

Chengfei Zhang,1,2,&ast; Qiue Zhang,3,&ast; Lingling Qin,4,&ast; Zhiyi Yan,5 Lili Wu,4,5 Tonghua Liu5 1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Technology Department, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tonghua Liu, Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Email thliu@vip.163.comBackground: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear.Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively.Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group.Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.Graphical Abstract: Keywords: dioscin, autoimmune thyroiditis, transcriptome, TLR4/NF-κB

Shengsheng Yao,1,&ast; Bo Zhang,2,&ast; Xiang Fei,3 Mingming Xiao,4 Li Lu,5 Daming Liu,6 Siyuan Zhang,7 Jianchun Cui3 1China Medical University - Department of Thyroid and Breast Surgery, Liaoning Provincial People’s Hospital, Shenyang, Liaoning Province, 110015, People’s Republic of China; 2Department of Science and Education, The 10th Division of Xinjiang Production and Construction Corps, Beitun General Hospital, Beitun City, Xinjiang Province, 831300, People’s Republic of China; 3Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 4Department of Pathology, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 5Department of Endocrinology, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 6Department of Ultrasound, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, Liaoning Province, 110015, People’s Republic of China; 7Department of Thyroid and Breast Surgery, The 10th Division of Xinjiang Production and Construction Corps, Beitun General Hospital, Beitun City, Xinjiang Province, 831300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianchun Cui, Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), No. 33 of Wenyi Road, Shenhe District, Shenyang, Liaoning Province, 110015, People’s Republic of China, Tel +86 24 24016014, Fax +86 24 24016014, Email cjc7162003@aliyun.comAbstract: The prevalence of antibody-negative chronic autoimmune thyroiditis (SN-CAT) is increasing. The early diagnosis of SN-CAT can effectively prevent its further development. Thyroid ultrasound can diagnose autoimmune thyroiditis and predict hypothyroidism. Primary hypothyroidism with a hypoechoic pattern suggested by thyroid ultrasound and negative thyroid serum antibodies is the main basis for the diagnosis of SN-CAT. However, for early SN-CAT, only hypoechoic thyroid changes and serological antibodies are currently available. This study explored how to achieve an accurate and early diagnosis of SN-CAT and prevent the development of SN-CAT combined with hypothyroidism. The diagnosis of a hypoechoic thyroid by artificial intelligence is expected to be a breakthrough in the accurate diagnosis of SN-CAT.Keywords: antibody negative, autoimmune thyroiditis, hypothyroidism, hypoechoic thyroid, artificial intelligence, Hashimoto’s disease

Background. In recent years, in Ukraine and other countries of the world, there has been an increase in the frequency of autoimmune thyropathies. A significant role in the pathogenesis of autoimmune thyroiditis (AIT) is played by cytokines whose production is increased significantly during immunopathological reactions. The purpose of study was to investigate the effect of the combined use of myo-inositol, vitamin D and selenium on the cytokine status of women with euthyroidism, subclinical hypothyroidism and overt hypothyroidism against the background of autoimmune thyroiditis. Materials and methods. One hundred and forty-seven women aged 18–43 with AIT and 30 women of the control group were under observation. Patients of first group (n = 74) received myo-inositol at a dose of 2000 mg/day, cholecalciferol 2000 IU/day, and selenium 100 μg/day additionally to the main treatment. Patients of the second group (n = 73) received only cholecalciferol at a dose of 2000 IU/day and selenium 100 μg/day additionally to the main treatment. The functional state of the thyroid gland was studied by determining the levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine, antibodies to thyroid peroxidase (Ab-TPO) and antibodies to thyroglobulin (Ab-TG). The state of the systemic and local inflammatory process was evaluated according to parameters of tumor necrosis factor α, interleukins 6, 10, 17, and 23. Results. It should be noted all patients with AIT had changes in cytokine status, with some differences depending on the clinical variant of autoimmune thyroid disease. After three months of treatment of patients of the first group with myo-inositol at a dose of 2000 mg/day, cholecalciferol 2000 IU/day and selenium 100 μg/day, and patients of the second group only with cholecalciferol at a dose of 2000 IU/day and selenium at 100 μg /day, a significant difference was found between the indicators in both studied cohorts. Conclusions. The administration of myo-inositol, vitamin D, and selenium had a combination effect on the reduction of cytokine indicators, Ab-TPO and Ab-TG levels, which contributed to the compensation of the underlying disease.

Selenium (Se) is an essential trace element of pivotal importance to human health. Se is incorporated into selenoproteins (SePs) which have pleiotropic effects, including antioxidant and anti-inflammatory effects, and in the production of active thyroid hormone. These findings may explain the relationship between Se deficiency and pathogenesis of various human diseases including thyroid disorder. In line with these observations, the therapeutic effectiveness of Se supplementation has already been reported in patients with various thyroid diseases. However, there are still controversial data about the optimal dose of Se to be administered, as well as the duration and efficacy of treatment and safety of this trace element. It is currently recommended to administer Se supplements following the assessment of any deficiency status of this element and, after that, its association with chronic autoimmune thyroid disease has been proven. Consistent with these observations, several clinical studies have highlighted the fact that Se supplementation in patients with chronic autoimmune thyroid disease was associated with a reduction of thyroid auto-antibodies, and with an improvement of the thyroid-associated ophthalmopathy. The beneficial effects of Se supplementation have been reported in subjects with thyroid disease during the hyperthyroid phase. The restoration of euthyroidism is a major goal in the management of thyrotoxicosis of Graves’ disease. In line with these observations, clinical studies have shown that, in patients with Graves' disease and autoimmune thyroiditis, treatment with a combination of anti-thyroid drugs and Se restore the euthyroid status faster than the administration of anti-thyroid drugs alone. The review shows that the treatment of an autoimmune thyroid disease with Se may bring about beneficial effects.

Helicobacter pylori (H. pylori) increases the risk of diseases associated with mucous membrane inflammation of gastrointestinal tract, in particular, gastritis, stomach ulcers, and duodenal ulcers. It may also induce a chronic immune response, causing damage to the mucous membrane and development of these diseases. In addition, the role of H. pylori in the initiation of a wide range of autoimmune diseases is discussed. The aim of this study was to assess the level of autoantibodies – markers of various autoimmune diseases in the blood of H. pylori-infected patients with chronic gastritis. We used samples of whole peripheral blood from 267 primary patients with chronic gastritis in the acute stage. The presence of H. pylori in gastric juice from patients was determined using real-time PCR. The level of autoantibodies to double-stranded and single-stranded DNA, autoantibodies to thyroglobulin, thyroid peroxidase, concentration of rheumatoid factor, IgG autoantibodies to the cyclic citrullinated peptide, IgM and IgG autoantibodies to beta(2)-glycoprotein were determined by the enzyme immunoassay. The average level of rheumatoid factor in blood serum was similar for H. pylori-infected and non-infected patients, and did not exceed the normal values. The level of antibodies to cyclic citrullinated peptide, one of the sensitive markers of rheumatoid arthritis, was increased in all patients, being, however, significantly lower in H. pylori-infected patients compared with non-infected persons. Autoantibodies to thyroglobulin, thyroid peroxidase are considered classic markers of autoimmune diseases of the thyroid gland. In blood of H. pylori-infected patients we have found an increased concentration of autoantibodies to thyroglobulin and thyroid peroxidase in comparison with non-infected ones, but the average level of these antibodies did not exceed the normal range. Any differences in the levels of systemic lupus erythematosus serological markers, i.e., autoantibodies to double-stranded and single-stranded DNA, were found between H. pylori-infected and non-infected patients. The levels of thrombosis risk marker in patients with systemic lupus erythematosus (IgG and IgM autoantibodies to beta(2)-glycoprotein) were also within the normal ranges. However, in H. pylori-infected patients, it even turned out to be statistically significantly lower than in non-infected ones. Thus, no data have been obtained on increased levels of the tested markers of autoimmune pathology in blood of H. pylori-infected patients with chronic gastritis at the acute stage. However, this does not allow us to make an unambiguous conclusion that the influence of H. pylori does not affect the development of immunological changes associated with autoimmune diseases.

Objective: To investigate the prognostic value of indicators from b-mode ultrasound, color Doppler ultrasound, and strain elastography of the thyroid gland in the diagnosis of Hashimoto's thyroiditis (HT). Methods: In 70 euthyroidal patients with HT, demographic characteristics, serum thyroid profile and ultrasound parameters, including thyroid gland size, vascularity and stiffness (elastography strain index) of the parenchyma, and flow indices of the superior and inferior thyroid artery were recorded. The control group consisted of 70 age and weight matched euthyroid individuals with negative anti-thyroid antibodies (anti-TPO and anti-Tg). Results: A significant difference was observed between the two groups in total thyroid size (ml, median ± standard deviation, SD) 7.86 ± 2.9 in HT vs. 6.35 ± 2.7 ml in controls, p = 0.003) and parenchymal vascularity which was increased in patients with HT (p 7.3 ml exhibited sensitivity of 61.43% and specificity of 72.6% for the diagnosis of HT. Conclusion: Patients with HT exhibit larger thyroid size and increased intrathyroidal vascularity on ultrasound prior to the manifestation of hypothyroidism compared to the healthy population. Flow indices of the superior thyroid artery do not have prognostic value in the diagnosis of HT.

BackgroundGlutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases.MethodsFor the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis.Case presentationAn 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications.ResultsAmong the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death.ConclusionOur findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes.

Autoimmune thyroiditis also named Hashimoto's thyroiditis: is an inflammatory disorder of the thyroid gland. It is characterized by circulating antibodies to thyroid antigens, and enlargement of the gland with lymphocytic infiltration. Regulatory T cells (Tregs), a particular subset of CD4+ T cells that express CD25 at a markedly increased level. they can regulate immune response in order to preserve homeostasis and self-tolerance. T cell expansion and cytokine production are restricted by Tregs. The development of this autoimmune disease is influenced by TGF-ß1 shortage. Management of HT is usually a symptomatic therapy that concentrates on HT's symptoms rather than its underlying cause. Statins, the lipid lowering medications have pleotropic effects. they can alter immunological reactions. Twenty-four female rats were used for this experiment divided into four groups (n=6), the disease was induced in all groups except group1 (control) where rats only received phosphate buffer saline, group 2 (induction group), group 3 received Prednisolone 2mg\kg orally for 30 days and group 4 received Simvastatin (4mg\kg) orally for 30 days too. Hashimoto’s thyroiditis was induced experimentally by subcutaneous injection of porcine thyroglobulin in Freund’s adjuvant emulsion (4mg/ml). Results showed an increase in Tregs and serum TGF-ß level in rats treated with simvastatin. In conclusion, simvastatin improves the number of functioning Tregs and increases TGF-ß signaling to suppress the autoimmune reaction. Therefore, simvastatin can be a promising approach in the treatment of this disease.

Background. Numerous studies have demonstrated that thyroid conditions can affect cognitive function. Gene polymorphisms associated with pathology of the endocrine and nervous system have ethnic and population specificity, which determines the need to study them in a certain region. The purpose of the study was to investigate the combined impact of the BDNF (rs6265), VDR (rs2228570), and NMDA (rs4880213) gene polymorphisms on cognitive impairment in patients with autoimmune thyroiditis and hypothyroidism among the population of Western regions of Ukraine, and to predict the onset of cognitive disorders. Materials and methods. The study involved a total of 153 patients with autoimmune thyroiditis and hypothyroidism. Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA (rs4880213) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) was performed on CFX96™ Real-Time PCR Detection System (Bio-Rad Laboratories, Inc., USA). Polymerase chain reaction for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). We detect a decline in cognitive function using the Mini-Mental State Examination. Results. Carrying a combination of CC/AG/CC genotypes significantly reduces the risk of developing cognitive impairment (odds ratio (OR) = 0.1410; 95% confidence interval (CI) 0.0181–1.0965; p = 0.0416). At the same time, carrying a combination of CT/AG/CT genotypes increases the risk of cognitive impairment by more than 5 times (OR = 5.1915; 95% CI 1.2471–21.6107; p = 0.0214) and a combination of CT/AG/TT genotypes — by 10 times (OR = 10.1224; 95% CI 1.1037–92.8401; p = 0.0281). Carriers of the CT/AA/CT genotype combination have a 6.4-fold increased risk of cognitive impairment (OR = 6.4062; 95% CI 1.2019–34.1471; p = 0.0253). Conclusions. Among patients with autoimmune thyroiditis and hypothyroidism, carriers of the CC/AG/CC genotype combination of the BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) genes have a reduced risk of developing cognitive disorders, while carriers of the CT/AG/CT, CT/AG/TT and CT/AA/CT have an increased risk of cognitive impairment.

Background: Hashimoto's encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis, is a relatively uncommon neurological disorder, mostly in adults, with an extremely rare occurrence in children. Clinical Description: A 9-year-old girl presented with unprovoked seizures and encephalopathy. She had been diagnosed with hypothyroidism, at around 6 ½ years of age, though was noncompliant to therapy with levothyroxine. Management: The child was managed with intravenous (IV) antiepileptics and other supportive care. Seizures were refractory and with worsening sensorium, she required mechanical ventilation. The magnetic resonance imaging of the brain was unremarkable, as also the cerebrospinal analysis. Autoimmune encephalitis panel was negative. The electroencephalogram showed background activity of 10–11 Hz and few areas with generalized slow waves. As she was a known case of hypothyroidism without taking thyroid supplements for the past few months, thyroid profile was sent. Reports showed FT3-1.1 pg/dL, FT4-0.515 ng/dL, and thyroid-stimulating hormone (TSH) - 107.3 μIU/mL. Thyroid antibody profile revealed antithyroid peroxidase antibody >500 IU/mL and antithyroglobulin antibody >1000 IU/mL. Following this, an ultrasound of the neck was done which showed features of thyroiditis. Considering the possibility that the underlying thyroiditis could explain the obtunded state and refractory seizures, the patient was started on levothyroxine and IV methylprednisolone. The sensorium of the child improved dramatically, and she got extubated. There were no further seizures and her TSH level reduced gradually and eventually, she was discharged. Conclusions: In a child with altered sensorium and refractory seizures, Hashimoto encephalopathy is a diagnosis of exclusion and may be considered when most of the common causes of encephalopathy and seizures have been ruled out, especially in the setting of some clinical clues of hypothyroidism. The condition is often reversible with good response to steroid therapy.

A review of data on the possible causes of an increase rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (ACCP) and antibodies to modified citrullinated vimentin (AMCV) in patients without rheumatoid arthritis (RA) is presented. The possibility of hyperproduction of these autoantibodies before the development of the clinical picture of RA was indicated. It is indicated that ACCP and IgA RF have the greatest prognostic value in terms of the subsequent development of RA. These antibodies are recommended to be additionally determined in diagnostically difficult cases. Data on the sensitivity and specificity of detection of RF, ACCP and AMCV in the diagnosis of RA are summarized. The results of detection of the discussed antibodies in various rheumatic (other than RA) and non-rheumatic diseases are presented in detail. Particular attention is paid to diseases in which increased synthesis of RF, ACCP and AMCV may not be accompanied by clear clinical symptoms (Sjögren’s disease, autoimmune thyroiditis, some chronic infections, silicosis, monoclonal gammopathy, etc.). Recommendations are given for examining patients with “accidentally” identified increase in RF or ACCP.

Hashimoto’s thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

(1) Autoimmune thyroiditis (AIT) is the most common cause of primary hypothyroidism and one of the most frequent organ-specific autoimmune diseases. Its pathogenesis is polygenic and still requires further research. The aim of the study was to assess, for the first time in the Caucasian population, the role of selected TPO gene promoter polymorphisms (rs2071399 G/A, rs2071400C/T, rs2071402 A/G, and rs2071403 A/G) in the development of AIT. A total of 237 patients diagnosed with AIT and 130 healthy controls were genotyped for four TPO gene polymorphisms, and the results were statistically analyzed to check for the role of these polymorphisms. There were no significant differences in the genotype and allele frequencies of the studied TPO gene promoter polymorphisms between patients and controls (p > 0.05). The haplotype distribution (rs2071400–rs2071402–rs2071403) between the two studied groups was similar for the most common variants (CGA, CAG, TGG). Only a rare haplotype (CGG) occurred more frequently among patients compared to controls (p = 0.04). The studied TPO gene promoter polymorphisms did not show an association with susceptibility to AIT in the Caucasian Polish population, contrary to the results in Japanese patients.

The gut microbiome may contribute to the development of autoimmune diseases, such as autoimmune thyroiditis (AIT). Diet has a critical impact on the gut microbiome, and it has been shown that a gluten-free diet can negatively affect its composition. A gluten-free diet is popular among patients, and therefore the aim of this study was to check whether it affects thyroid function and gut microbiome composition in AIT. Thirty-one women with AIT complied with a gluten-free diet for 8 weeks. After the first 4 weeks, participants were divided into two groups: the first group received gluten in capsules and the other one—rice starch (placebo). Blood and stool samples were examined before diet (T0), after 4 weeks (T1) and after 8 weeks of diet (T2). The only significant difference in blood parameters was observed between T1 and T2 in the placebo group for the thyroid peroxidase antibody level. After the first 4 weeks, a significant increase in Desulfobacterota, Proteobacteria, Prevotella and Parasutterella and a significant decrease in Actinobacteriota, Coriobacteriaceae and Bifidobacterium were observed. The detected microbiome alterations may indicate increasing inflammation; however, further research is required, and for now, a gluten-free diet should be used cautiously in AIT.

BackgroundHashimoto’s thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other gluten-related conditions (GRC). In the last years, interest about gluten-free diet (GFD) has increased for its supposed extraintestinal anti-inflammatory effect; thus, many patients with HT initiate GFD on their own.ObjectivesThe aim of this meta-analysis is to examine all available data in literature about the effect of a GFD on TgAb, TPOAb, TSH, FT4, and FT3 levels in patients with HT and no symptoms or histology of CD.MethodsThe study was conducted according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology). The search was performed on databases PubMed and Scopus. The last search was performed on 7 February 2023. Quality assessment was performed. Meta-analyses were performed using the random-effect model. Hedges’ g was used to measure the effect size (ES). Statistical analyses were performed using StataSE 17.ResultsThe online search retrieved 409 articles, and 4 studies with a total of 87 patients were finally included for quantitative analysis. The risk of bias was generally low. The mean period of GFD was almost 6 months. The meta-analyses showed reduction in antibody levels with ES: −0.39 for TgAb (95% CI: −0.81 to +0.02; p = 0.06; I² = 46.98%) and −0.40 for TPOAb (95% CI: −0.82 to +0.03; p = 0.07; I² = 47.58%). TSH showed a reduction with ES: −0.35 (95% CI: −0.64 to −0.05; p = 0.02; I² = 0%) and FT4 showed an increase with ES: +0.35% (95% CI: 0.06 to 0.64; p = 0.02; I² = 0%). FT3 did not display variations (ES: 0.05; 95% CI: −0.38 to +0.48; p = 0.82; I² = 51%). The heterogeneity of TgAb, TPOAb, and FT3 data was solved performing sub-analyses between patients with or without GRC (TgAb p = 0.02; TPOAb p = 0.02; FT3 p = 0.04) and only for FT3, performing a sub-analysis between patients taking and not taking LT4 (p = 0.03).ConclusionThis is the first meta-analysis investigating the effect of GFD on HT. Our results seem to indicate a positive effect of the gluten deprivation on thyroid function and its inflammation, particularly in patients with HT and GRC. However, current lines of evidence are not yet sufficient to recommend this dietary approach to all patients with a diagnosis of HT.

The article presents a description of a patient with chronic HCV infection and multiple extrahepatic manifestations, which manifested in dynamics and were recorded with a different sequence during 15 years of follow-up. In the patient we observed, the most frequently recorded extrahepatic manifestations were verified: porphyria cutanea tarda, mixed cryoglobulenemia, and utoimmune thyroiditis. Chronic HCV infection is often diagnosed in the presence of psoriasis was assessed as a paraneoplastic disease.