Search

The principles and effectiveness of the method of laser polarization interferometry of dehydrated blood films (facies) for the differential diagnosis of thyroid pathology have been studied. For this purpose, a theoretical description of the processes of formation and layer-by-layer phase scanning of the polarization structure of speckle fields in the blood facies of donors and patients with nodular goiter, autoimmune thyroiditis, and papillary cancer has been developed for the first time. A statistical analysis of holographically reconstructed maps of polarization ellipticity of the singly scattered component of the speckle field was conducted. Based on this analysis, the most sensitive markers for the diagnosis and differentiation of thyroid pathology were identified. Excellent diagnostic accuracy (91%–93%) and very good differentiation accuracy (86%–89%) were achieved for nodular goiter, autoimmune thyroiditis, and papillary cancer. [ABSTRACT FROM AUTHOR]

Objective: The main objective was to assess the therapeutic efficacy of selenium alone versus a combination of myo-inositol and selenium (MI + Se) in treating patients with autoimmune thyroiditis (AIT). The study aims to determine which treatment option is more effective in restoring euthyroid state, as indicated by changes in thyroid-stimulating hormone (TSH), T3, T4, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) Methods: Google Scholar and PubMed databases were searched for randomized controlled trials (RCTs) and observational studies that reported outcomes of combined treatment (MI + Se) in restoring a euthyroid state, specifically comparing it with selenium-only (Se-only) treatment. Changes in TSH, T3, T4, TPOAb, and TgAb levels from baseline were defined as indicators to compare the effect of combined versus selenium-only treatment in restoring euthyroid levels. The Cochrane risk of bias tool and Newcastle Ottawa Scale were used to assess the quality of the randomized control trials included in the study. Review Manager (version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark) was used for statistical analysis. Result: We pooled three studies, enrolling 151 participants in the MI + Se group and 137 participants in the Se group. Supplementation of Se with MI demonstrated a significant reduction in TSH levels compared to Se alone (SMD = −1.15, 95% CI: −1.60 to −0.69, P <.00001). MI + Se treatment also significantly reduced TgAb levels compared to Se (SMD = −0.51, 95% CI: −0.78 to −0.24, P =.0002). In contrast, TPOAB, T3 and T4 levels were non-significantly reduced from baseline in patients treated with MI + Se when compared to Se alone (SMD = −0.81, 95% CI: −0.44 to 0.09, P =.20), (SMD = 0.16, 95% CI: −0.09 to 0.42, P =.22), and (SMD = 0.30, 95% CI: −0.23 to 0.83, P =.26) respectively. Conclusion: Supplementation of Se with MI showed a significant reduction in TSH and TgAb levels compared to selenium-only treatment, with a non-significant reduction in TPOAB, T3, and T4 levels. This entails the need for powered clinical trials and observational studies with longer follow-ups to critically assess the role of combined therapy in restoring euthyroid state in patients with AIT. Plain Language Summary: Summary of Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis The study aimed to determine whether taking the supplementation therapy of myo-inositol and selenium (MI+Se) together is more effective than taking selenium alone for people suffering from autoimmune thyroiditis, a condition in which the immune system attacks the thyroid gland and often leads to hypothyroidism. Researchers reviewed relevant studies from Google Scholar and PubMed, focusing on randomized control trials (RCTs) and observational studies that compared the effects of selenium alone versus selenium plus myo-inositol. They analyzed changes in thyroid-related blood markers TSH, T3, T4, TPOAb, and TgAb levels) to assess effectiveness of the given therapy. The study included three RCTs with 288 participants that were assessed through the supplementation therapy of selenium alone and myo-inositol plus selenium (MI+Se). Findings suggest that the combination of selenium and myo-inositol significantly reduced TSH levels, which indicates thyroid activity and improvement in the condition, more than selenium alone. It also lowered TgAb levels, antibodies that attack the thyroid, more effectively than selenium alone. However, the two groups had no significant changes in other markers like TPOAb, T3, and T4. The results suggest that the combination treatment might be more effective in reducing harmful antibodies and improving thyroid function compared to selenium alone. This finding is particularly relevant for managing AIT and improving thyroid health, pointing to potentially better treatment strategies. Nevertheless, the study emphasizes the need for more extensive and longer-term research to confirm these benefits and fully understand the implications. This research highlights the promise of combining supplementation with selenium and myo-inositol as a more effective approach for people with autoimmune thyroiditis (AIT). This could lead to improved management and outcomes for this common thyroid condition. [ABSTRACT FROM AUTHOR]

Ring chromosome 18 (r(18)) is a rare chromosomal abnormality characterized by the circular rearrangement of chromosome 18, which presents significant challenges in genotype-phenotype correlations due to variability in deletions across the 18p and 18q arms. We report the case of a pediatric patient with a de novo ring chromosome 18, diagnosed by karyotype analysis and confirmed by high-resolution SNP arrays. The patient exhibited pathogenic copy number variants (CNVs) in the 18p11.32p11.22 and 18q23 regions, involving 36 and 10 OMIM genes, respectively. Clinically, the patient presented with hypothyroidism secondary to autoimmune thyroiditis, autoimmune hepatitis type II, and genetic predisposition to celiac disease and insulin-dependent diabetes mellitus (IDDM) along with notable dysmorphic features. The 18q microdeletion encompasses the MBP gene, involved in the development and functionality of the nervous system, as supported by hypotonia and gliosis shown by the MRI. This case highlights the complex interplay between genetic imbalances on chromosome 18 and autoimmune phenotypes, emphasizing the need for ongoing research to elucidate underlying mechanisms and optimize clinical management for individuals with r(18). [ABSTRACT FROM AUTHOR]

Background: Mogamulizumab is a monoclonal antibody targeting the C‐C chemokine receptor 4, used to treat T‐cell malignancies such as cutaneous T‐cell lymphoma, adult T‐cell leukemia/lymphoma, and peripheral T‐cell lymphoma. However, real‐world studies on mogamulizumab‐associated adverse events (AEs) are limited. Methods: Disproportionality analyses were performed to assess the safety profile of mogamulizumab based on data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for the period spanning from October 2018 to December 2023. The research investigated demographic characteristics, the onset timing of AEs, and the safety implications associated with mogamulizumab use. Results: A total of 1182 significant preferred terms were identified among the 3661 mogamulizumab‐associated AE reports collected from the FAERS database. The frequently reported AEs including rash, infusion‐related reaction, and pyrexia were in line with drug instruction. Notably, several unexpectedly significant AEs were also found, including pemphigoid (ROR = 5.69 [95% CI 1.83–17.66]), unstable angina (ROR = 20.56 [95% CI 8.54–49.5]), bulbar palsy (ROR = 238.36 [95% CI 75.22–755.31]), myositis (ROR = 12.65 [95% CI 5.67–28.19]), and various autoimmune diseases such as autoimmune hepatitis (ROR = 21.33 [95% CI 11.08–41.07]), myocarditis (ROR = 15.29 [95% CI 8.67–26.97]), glomerulonephritis (ROR = 22.49 [95% CI 7.24–69.9]), nephrotic syndrome (ROR = 7.63 [95% CI 2.46–23.67]), myasthenia gravis (ROR = 8.54 [95% CI 3.2–22.77]), and autoimmune thyroiditis (ROR = 11.81 [95% CI 3.8–36.68]). Conclusion: This study replicated previously identified AEs associated with mogamulizumab and uncovered additional signals of AEs, particularly emphasizing the risks associated with autoimmune diseases. It is essential to exercise vigilance in monitoring the occurrence of these AEs during the use of mogamulizumab in clinical practice. [ABSTRACT FROM AUTHOR]

Autoimmune 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. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets. Methods: We recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT. Results: Integrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis. Conclusion: Our study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder marked by chronic inflammation of the thyroid gland, predominantly affecting children and adolescents. In a previous study, we developed a "maximal" mathematical model of thyroid physiology to simulate the complex interactions within the thyroid gland. The present research introduces an enhanced version of the "maximal" model, integrating the pathophysiological impacts of HT. It specifically models the adverse effects of thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (TPOAb and TgAb) on TPO, Tg, sodium iodide symporter (NIS), albeit indirectly, and thyroid volume. Additionally, we present a new "minimal" model offering a streamlined interpretation of thyroid physiology and pathophysiology, designed for faster computational analysis while maintaining essential physiological interactions. Both models were fitted against longitudinal clinical data from patients with HT, assessing the concentrations of Thyroid Stimulating Hormone (TSH), Thyroxine (T4), and thyroid volume over 36 months, in both untreated patients and those receiving levothyroxine (LT4) treatment. The adaptation of the models to data shows that both of them accurately reproduce the available observed clinical outcomes, with the "maximal" model providing more detailed physiological insights but requiring extensive data and longer computation times. In contrast, the "minimal" model, despite exhibiting less realistic TSH oscillations, offers rapid parameter estimation and may be more feasible in clinical settings. These models hold significant potential as tools for detailed study and management of HT, enabling simulations of disease progression and therapeutic responses, thus paving the way for personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is an autoimmune disease, characterized by abnormal elevation in thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). Patients have multiple symptoms despite adequate hormone substitution. In the present study, we aimed to quantify the relationship between thyroid antibodies and multiple symptoms, inflammation and health-related life quality. A total of 108 HT patients with clinical euthyroid status and 57 heathy controls were recruited. Clinical parameters were determined by laboratory examination, and the symptoms burden and life quality were obtained by a Hashimoto's Thyroiditis Symptom Questionnaire and a SF-36 Questionnaire, respectively. Compared with healthy controls, multiple extrathyroidal symptoms were significantly more serious in HT patients despite euthyroid status, mainly including that related to digestive system (abdominal distension, constipation and diarrhea), endocrine system (chilliness, gain weight and facial edema), neuropsychiatric system (forgetfulness, anxiety, depressed, fatigue, insomnia, irritability, and indifferent) and mucocutaneous system (dry skin, pruritus, and hair loss). Furthermore, serum TPO-Ab and TG-Ab were both inversely correlated with health-related life quality of general health and vitality parameters, and positively correlated with pro-inflammatory factors of TNF-α and IFN-γ, as well as severity of abdominal distension, diarrhea, chilliness, forgetfulness and fatigue. Moreover, TG-Ab level was positively associated with depressed, insomnia and indifferent. HT patients suffered from a variety of symptoms, and the elevated thyroid antibodies were inversely associated with health-related life quality and positively associated with inflammation and multiple extrathyroidal symptoms. [ABSTRACT FROM AUTHOR]

Objective: The relationship between post-traumatic stress disorder (PTSD) and autoimmune thyroid disease (AITD) needs further evaluation. This study employs Mendelian randomization (MR) to investigate the causal correlations of PTSD with autoimmune thyroiditis (AIT) and Graves' disease (GD). Methods: Datasets for PTSD, AIT, and GD were obtained from FinnGen. The exposure-outcome causal relationship was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was evaluated through the MR-Egger intercept, heterogeneity was examined using Cochran's Q test, and robustness was assessed via leave-one-out sensitivity analysis. Results: MR analysis indicated no significant causal relationship between PTSD and AIT (OR 0.920, 95% CI 0.832 to 1.017, p = 0.103), but a potential increase in the risk of GD associated with PTSD (OR 1.056, 95% CI 1.008 to 1.105, p = 0.021). MR-Egger intercept showed no horizontal pleiotropy (p > 0.05), and Cochran's Q showed no heterogeneity (p > 0.05). Sensitivity analysis suggested the MR results were robust. Conclusions: Evidence of an MR association between genetic liability to PTSD and an increased risk of GD were provided, but no evidence of association between PTSD and AIT. The findings indicate that individuals with PTSD may have an increased likelihood of developing GD, underscoring the importance of further research to comprehend the intricate interplay between PTSD and thyroid disorders. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the risk factors and metastatic patterns in papillary thyroid cancer (PTC) patients undergoing lymph node dissection, offering guidance for clinical practice. Methods: A total of 924 PTC patients who underwent thyroidectomy with central neck dissection (CND) or lateral neck dissection (LND) between January 2021 and November 2022 were included in the analysis. The study investigated the relationships between clinicopathological characteristics, lymph node metastasis, and various risk factor. Results: Among the 924 PTC patients, the cervical lymph node metastasis rate was 59.1% (546 patients). Of these patients, 381 had central neck metastasis (CNM, 41.2%), while the remaining 165 patients had lateral neck metastasis (LNM, 17.9%). Factors associated with increased risk of CNM and LNM included larger tumor diameter, presence of multiple tumors, and capsular invasion (p<0.05). Male sex, age <55 years, larger tumor diameter (>0.85 cm), multiple tumors, capsular invasion, and absence of Hashimoto's disease were identified as independent risk factors for CNM (p<0.05), with an AUC value of 0.722. CNM, maximum diameter >1.15 cm, and multiple tumors were independent risk factors for LNM (p<0.05), with an AUC of 0.699. Conclusion: These findings suggest that tailored neck dissection based on individual risk factors is crucial, particularly in cases of suspected LNM with larger tumors, CNM, multiple tumors, and capsular invasion. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR). Methods: Single nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran's Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively. Results: Forward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn's disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran's Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results. Conclusion: This MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT. [ABSTRACT FROM AUTHOR]

Background: Amid the large panel of autoimmune thyroid diseases, Hashimoto's thyroiditis (HT) represents a major point across multidisciplinary daily practice. When it comes to the clinical picture, particularly in regard to asthenia (also described as "fatigue" or "decreased energy"), the differential diagnosis is challenging, and a meticulous anamnesis should be backed up by focused lab investigations. Our objective was to analyze the thyroid panel in newly diagnosed patients with HT in relationship with the presence of asthenia as an admission complaint. Methods: This was a retrospective, multi-centric, real-life study conducted in secondary endocrine units (university hospitals) from July 2022 to July 2023. The exclusion criteria were COVID-19 infection; an active malignancy, etc. Results: The cohort (N = 120) included an asthenia group (AS, 49.2%) and a non-AS group of a similar age (49.3 ± 14.7 vs. 47.1 ± 14.8 y, p = 0.426). Headache was more frequent in the AS group (35.6% vs. 18%, p = 0.03). Thyroid function and HT-related antibodies assays were similar between the groups and show no correlation with serum total cholesterol and triglycerides, respectively. TSH levels did not vary among the age sub-groups (p = 0.701). One third of the studied population was affected by hypothyroidism (TSH > 4.5 μIU/mL), being seen at a higher rate in the AS (39%) vs. non-AS group (23%). Total cholesterol positively correlated with the patients' age (r = 0.180, p = 0.049) and triglycerides (N = 120; r = 0.324, p < 0.001), as found only in the non-AS group (r = 0.246, p = 0.006, respectively, r = 0.319, p < 0.001). Conclusions: The analysis of the AS vs. non-AS group pinpointed the fact that, in regard to daily practice, asthenia as an admission complaint seems less of an indicator of an underlying thyroid dysfunction or a higher level of serum antibodies against thyroid in patients without a full clinical picture of thyrotoxicosis or myxoedema. [ABSTRACT FROM AUTHOR]

ABSTRACT: Introduction: Anti-thyroid antibodies not only cause thyroid dysfunction but have independent adverse outcomes in the fetus and mother during pregnancy and after birth. Chronic lymphocytic thyroiditis as a presentation of immune system deregulation may be associated with a generalized activation of the immune system at the fetus–maternal unit, the placenta. This interference could be associated with pregnancy morbidities in m o t h e r a n d fetus. This study was done to find out the frequency of autoimmune thyroid disease and its effect on maternal and fetal outcomes in a tertiary care facility in Jharkhand. Method: This is an Observational Prospective Study done during an 18-month period on 254 pregnant women in their second trimester who came to the antenatal clinic (ANC) clinic with singleton pregnancy at RIMS Ranchi. Result: 222 (87.4%) out of the 254 pregnant women had anti- TPO antibodies less than 35 IU/ml. Anti-thyroid peroxidase (anti-TPO) antibody positivity with values greater than 35 IU/ml was found in 32 patients (12.6%). Anti-TPO antibody mean value was 22.54 ± 19.67 IU/ml. Among the 222 individuals who tested negative for the anti-TPO antibody, 7 (3.3%) had miscarriages, 182 (88.3%) gave birth vaginally, and 33 (14.9%) underwent a cesarean section. Of the 32 individuals who tested positive for the anti-TPO antibody, 2 (6.3%) had miscarriages, 24 (75.0%) had vaginal deliveries, and 6 (18.8%) had cesarean sections. Using the Chi-square test, a P value of 0.549 was calculated, indicating statistical insignificance (Pearson Chi-square test value = 0.200a). Conclusion: Anti-TPO antibody positivity was significantly related to miscarriage and anemia. Other complications like preterm delivery, pre-eclampsia, and low birth weight were higher in anti-TPO antibody-positive patients as compared to anti-TPO antibody-negative patients. However, these findings were not statistically significant. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the epidemiological, clinical, laboratory, and radiological characteristics of children diagnosed with Hashimoto’s thyroiditis and to present the experiences of a referral center. Materials and Methods: This study included 200 pediatric patients diagnosed with Hashimoto’s thyroiditis between January 2020 and May 2024 at a single center. The data were extracted and compiled from the participants’ medical records, including clinical information, physical examination findings, laboratory test results, and radiological imaging. Results: Mean age of the study population was 11.3 ± 3.2 years at diagnosis, with a female predominance. At the time of clinical presentation, 8.5% of the study participants were 6 years of age or younger. The majority of patients, comprising 39.5% of the cohort, exhibited euthyroid thyroid function. Additionally, 33.5% of the patients were classified as having subclinical hypothyroidism, 22% demonstrated overt hypothyroidism, and 5% presented with hyperthyroidism. Approximately one-third of the study participants were referred for further evaluation due to the identification of abnormal thyroid function test results during routine screening examinations. 48% of the patients had a documented family history of thyroid disease. At diagnosis, 39.5% were prepubertal. The rate of overt hypothyroidism was higher in prepubertal patients compared to pubertal patients (41.8% vs. 9.1%, P < .005). Mean gland volume SDS was 2.61 ± 3.69, and 45.5% had goiter. Thyroid nodular lesions were identified in 5.5% of the study participants. Fine-needle aspiration biopsy was performed on five patients, revealing benign findings in three cases and atypia of undetermined significance in the remaining two cases. Conclusion: Patints with subclinical hypothyroidism who have a baseline TSH level exceeding 8.5 mIU/L at initial presentation and do not receive treatment are likely to progress to overt hypothyroidism during subsequent follow-up. Prepubertal cases were more frequently observed compared to previous reports, and the course of hypothyroidism was more severe in prepubertal patients. These findings suggest a potential shift towards earlier onset of autoimmunity in children. Further studies are warranted to substantiate this observation. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism (HT) affects millions worldwide and can lead to various lipid disorders. The metabolic complexity and the influence of toxic elements in autoimmune and non-autoimmune HT subtypes are not fully understood. This study aimed to investigate the relationships between plasma lipidome, toxic elements, and clinical classifications of HT in unexposed individuals. Methods: Samples were collected from 120 adults assigned to a study group with Hashimoto's disease and non-autoimmune HT, and a healthy control group. Quantification of 145 pre-defined lipids was performed by using triple quadrupole tandem mass spectrometry (TQ MS/MS) in multiple reactions monitoring (MRM) mode via positive electrospray ionization (ESI). Levels of toxic elements were determined using inductively coupled plasma mass spectrometry (ICP-MS). Results: Significant associations between altered levels of several components of the plasma lipidome and Al, Cd, Ni, As, and Pb with HT were found. We show metabolic differences in lysophosphatidylcholines (LPC) and phosphatidylcholines (PC) between HT and controls, with distinct predicted activation patterns for lysolecithin acyltransferase and phospholipase A2. Conclusions: There are significant changes in the lipidome profiles of healthy subjects compared to euthyroid HT patients treated with L-thyroxine, which are related to the type of hypothyroidism and non-occupational exposure to toxic elements. [ABSTRACT FROM AUTHOR]

Introduction: Immunotherapy is one of the greatest advancements in oncological patient care. The broader the treatment application, the more common the adverse events associated with the therapy. Immune checkpoint inhibitors (ICI) are currently used in numerous malignancies. These drugs influence the immune cells' interactions, which translates to interruption of immune evasion and increased anti-tumor activity. However, the disruption of immunological signaling pathways often leads to adverse events, such as endocrinological insufficiencies, among which thyroid is the most common. Moreover, the co-appearance of several insufficiencies has been previously described. Case report: A 73-year-old female treated with durvalumab due to non-small cell lung carcinoma was admitted to the emergency unit due to symptoms of ketoacidosis. She had a history of well-controlled type 2 diabetes mellitus and autoimmune thyroiditis. Laboratory results showed increased anti-GAD antibodies, while the low C-peptide level indicated type 1 diabetes mellitus. Moreover, over the course of longer observation, the patient presented with abrupt aggravation of her autoimmune thyroiditis. Conclusions: The new onset of endocrinological insufficiencies is a rare adverse event of immunotherapy. Clinicians must pay particular attention to any signs indicating these life-threatening conditions. In case of the appearance of any endocrinological adverse event, the close cooperation of oncologists and endocrinologists is required to enhance patients' quality of life. [ABSTRACT FROM AUTHOR]

The editorial discusses the latest research on cancer biology and therapeutics, focusing on various antitumor strategies presented in the second edition of the Special Issue. Studies cover different therapeutic approaches for papillary thyroid carcinoma, colorectal cancer, breast cancer, prostate cancer, pancreatic cancer, glioma, bladder cancer, and ovarian cancer. Researchers highlight the importance of molecular therapies, drug combinations, proteomics, local anesthetics, novel compounds, peptides, PARP inhibitors, and the control of APC/C-CDC20 activity in developing potential antitumor treatments for various types of cancer. The findings aim to improve early detection, personalized treatments, and clinical outcomes for cancer patients. [Extracted from the article]

The potential modulation of thyroid inflammatory conditions via a gluten-free diet has been suggested after establishing a link between Hashimoto's thyroiditis (HT) and celiac disease. However, the majority of targeted studies in this field do not support the general recommendation of prescribing a gluten-free diet (GFD) for all HT patients. This study aims to analyze data regarding the impact of a GFD supplemented with eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), along with vegetables, on the course of inflammation involving long-chain fatty acid mediators. The study cohort consisted of 39 Caucasian female patients with autoimmune HT. Metabolite separations were performed using a liquid chromatograph with a DAD detector. Absorption peaks were read at 210 nm for resolvin E1, protectin DX, and maresin 1 and at 302 nm for resolvin D1. The introduction of a gluten-free diet completed with omega-3, including EPA and DHA, may contribute to a reduction in the inflammatory state in HT patients. This effect is supported by the elevation in the levels of anti-inflammatory mediators derived from long-chain fatty acids with anti-inflammatory properties but not by eliminating gluten. Significant statistical changes in the levels of all derivatives were observed before and after the implementation of the diet. It is worth noting that this effect was not observed in anti-TPO and anti-TG levels. The induction of anti-inflammatory changes can be achieved by supplementing the diet with EPA, DHA and vegetables with increased anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital "R. Dulbecco" in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Vitiligo is an autoimmune disease characterized by the loss of skin pigmentation. This study aims to explore genetic associations between vitiligo and 21 autoimmune diseases using Mendelian randomization (MR) analysis, with a focus on identifying potential risk and protective factors. Methods: We performed univariable and multivariable Mendelian randomization analyses to assess the causal associations between 21 autoimmune diseases and vitiligo. Confounding factors, including smoking, alcohol consumption, and Body Mass Index (BMI), were integrated into the multivariable analysis. Strongly associated single nucleotide polymorphisms (SNPs) were mapped to genes, followed by Summary-data-based Mendelian Randomization (SMR) analysis with expression Quantitative Trait Loci (eQTL) and methylation Quantitative Trait Loci (mQTL) data. Risk and protective factors were further identified by evaluating inflammatory mediators and immune cell phenotypes. Results: The MR analysis identified seven autoimmune diseases with potential causal associations with vitiligo. However, after accounting for confounding factors, only Hashimoto's thyroiditis and type 1 diabetes maintained genetic associations with vitiligo. Gene mapping revealed 25 intersecting genes between these two diseases and vitiligo. SMR analysis confirmed Sulfite Oxidase (SUOX) as a protective gene across multiple tissues. Furthermore, several inflammatory factors were identified as risk factors, including C-X-C motif chemokine ligand 9 (CXCL9), C-X-C motif chemokine ligand 10 (CXCL10), Tumor Necrosis Factor (TNF), and Signaling Lymphocytic Activation Molecule (SLAM). In contrast, Osteoprotegerin (OPG) was identified as a protective factor. Discussion: This study provides novel insights into the shared molecular mechanisms linking vitiligo with other autoimmune diseases. The identification of SUOX as a common protective gene and the discovery of specific inflammatory and immune-related factors may facilitate future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: We evaluated correlations of occupational physical activity (OPA) and recreational exercise (RE), respectively, with thyroid function in patients with Hashimoto's thyroiditis (HT). Methods: We included 438 individuals with clinically diagnosed HT. Information on OPA and RE were collected through a self-report questionnaire. We assessed correlations between clinical phenotypes (TSH, T3, T4, fT4, TgAb, TPOAb, thyroid volume, vitamin D) and physical activities (OPA and RE) in all HT patients (ALL) and in two severity-based subgroups of patients (MILD and OVERT). Results: The main novel findings are significant correlations between increase in OPA and (i) a decrease in fT4 (OVERT, r = −0.265, p = 0.0002 and ALL, r = −0.138, p = 0.006); (ii) an increase in TSH (ALL, r = 0.124, p = 0.014 and OVERT, r = 0.183, p = 0.013) and (iii) an increase in TPOAb antibodies (ALL, r = 0.101, p = 0.045). In contrast, we observed correlations between increase in RE and: (i) a decrease in TSH (OVERT, r = −0.238, p = 0.001); (ii) a decrease in TgAb antibodies (OVERT, r = −0.194, p = 0.01) and (iii) an increase in vitamin D levels (ALL, r = 0.146, p = 0.005 and OVERT, r = 0.173, p = 0.023). Conclusions: Our results suggest that, unlike RE, OPA correlates with decreased thyroid function and increased thyroid autoimmunity. Our study proposes that the PA health paradox also applies for the thyroid health. [ABSTRACT FROM AUTHOR]

Objective: Ulcerative colitis (UC) and Hashimoto's thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. Methods: We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran's Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Results: Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36–69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Conclusion: Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells. [ABSTRACT FROM AUTHOR]

Purpose: Hashimoto's thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs), influenced by environmental factors, genetics, and the immune system. Previous research has shown a correlation between gut microbiota and HT, as well as the involvement of immune cells in its onset and progression. We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT. Methods: In this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the relationship between gut microbiota and HT using data from genome-wide association studies (GWAS) and the MiBioGen study. Subsequently, MR analyses were performed to investigate the interactions between 731 immune cells and gut microbiota. Additionally, an MR analysis was performed to examine the association between HT and these 731 immune cells, using a GWAS dataset that included 3,757 European subjects. This approach provided insights into the impact of 22 million genetic variants on 731 immune cell signatures. Results: There was a causal relationship between the increase in the number of 15 gut microbiota and HT. We observed that the genus Akkermansia, family Alcaligenaceae, family Desulfovibrionaceae, family Verrucomicrobiaceae, class Verrucomicrobiae, order Verrucomicrobiales, phylum Verrucomicrobia, class Alphaproteobacteria, order Desulfovibrionales, genus Ruminococcus torques group, genus Butyrivibrio, and genus Coprococcus3 were negatively correlated with HT. In addition, the genus Intestinimonas, genus Turicibacter, and genus Anaerostipes were positively correlated with HT. We identified EM CD4 + T cells as a mediator between the gut microbiota and HT. Conclusion: In conclusion, we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT, as inferred from the MR findings derived from extensive aggregated GWAS data. Our research offers guidance and direction for treating and preventing HT. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Recent studies have indicated a potential association of hypertension with Hashimoto's thyroiditis (HT) and other autoimmune diseases, yet the impact of antihypertensive drugs on HT risk is not well understood. Methods: We employed a drug-target Mendelian randomization approach to investigate the prolonged impact of 9 classes of antihypertensive medications on HT susceptibility in European and Asian populations. Genetic variants close to or within genes associated with the drug targets and systolic blood pressure (SBP) were utilized to mimic the effects of antihypertensive medications. We focused on drugs linked to a lower risk of coronary artery disease for our main analysis. We gathered genetic data on SBP and HT risk from comprehensive genomewide association studies available for European and Asian groups. For a supplementary analysis, we used expression quantitative trait loci (eQTLs) related to drug target genes as proxies. Results: Our analysis revealed that the use of calcium channel blockers (CCBs) is linked to a reduced risk of HT in both European (OR [95% CI]: 0.96 [0.95 to 0.98] per 1 mmHg decrease in SBP; p = 3.51×10-5) and Asian populations (OR [95% CI]: 0.28 [0.12, 0.66]; p = 3.54×10-3). Moreover, genetically mimicking the use of loop diuretics (OR [95% CI]: 0.94 [0.91, 0.97]; p = 3.57×10-5) and thiazide diuretics (0.98 [0.96, 0.99]; p = 3.83×10-3) showed a significant association with a decreased risk of HT only in European population. These outcomes were confirmed when eQTLs were employed to represent the effects of antihypertensive medications. Conclusion: The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system's structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota–thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation. [ABSTRACT FROM AUTHOR]

Background: Schwannomas are well‐encapsulated, solitary tumors that grow slowly from the nerve sheath. Sellar schwannomas tend to be mistaken for other sellar/parasellar lesions due to similar clinical and radiological findings. The present article describes the clinical presentation, radiological findings, histopathological features, and outcome of a patient with sellar schwannoma. Case Description: A 23‐year‐old female, known to have hypothyroidism secondary to Hashimoto's thyroiditis, presented with multiple episodes of galactorrhea, weight gain, and irregular menstrual cycle for 8 months. It was associated with decreased visual acuity and episodic headaches. Neurological examination revealed no focal deficits. Brain magnetic resonance imaging (MRI) showed a well‐defined lobulated lesion in the sellar region, compressing the right optic nerve and optic chiasm. The patient underwent craniotomy and tumor resection. The histopathological sections were diagnostic of schwannoma. Postoperatively, the patient noted a subjective improvement in her visual acuity. She was discharged in stable condition with regular follow‐ups at neurosurgery, endocrine, and ophthalmology clinics. Conclusion: Schwannoma of the sellar region is rare and can be misdiagnosed as pituitary adenomas. Preoperative hormonal profile and meticulous neuroradiological assessment narrow down the differential diagnosis for patients with sellar lesions. The diagnosis of sellar schwannomas is established with histopathology and immunohistochemistry results. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the correlation between Hashimoto's thyroiditis and Metabolic dysfunction-associated fatty liver disease (MAFLD), and at the same time to screen high-risk groups for liver fibrosis in MAFLD, find out the high-risk related indicators. The physical examination population was included as the study subjects and was grouped according to the diagnostic criteria for MAFLD. APRI > 1 or NFS > 0.676 or FIB-4 > 2.67were used to assess people at high risk of liver fibrosis, and logistic regression analysis was used to identify risk factors associated with high risk of liver fibrosis in MAFLD. ROC curves are used to look for indicators of diagnostic value. The proportion of people with Hashimoto's thyroiditis was lower in the MAFLD group. The MAFLD high-risk group for liver fibrosis had higher TSH levels, lower FT3 and FT4 levels, higher TGAB levels, and differences in biochemical markers. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients. ROC curve analysis showed that the AUC of age was 0.741 (0.721–0.761), and the optimal stage value was 57.5 years, while the AUC of AST was 0.729 (0.707–0.751), and the optimal cut-off value was 39.5 U/L. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients.The age is greater than or equal to 57.5 years, or the AST is greater than or equal to 39.5 U/L, indicating that the MAFLD patients are at high risk of liver fibrosis. [ABSTRACT FROM AUTHOR]

Objective: The relationship between post-traumatic stress disorder (PTSD) and autoimmune thyroid disease (AITD) needs further evaluation. This study employs Mendelian randomization (MR) to investigate the causal correlations of PTSD with autoimmune thyroiditis (AIT) and Graves' disease (GD). Methods: Datasets for PTSD, AIT, and GD were obtained from FinnGen. The exposure-outcome causal relationship was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was evaluated through the MR-Egger intercept, heterogeneity was examined using Cochran's Q test, and robustness was assessed via leave-one-out sensitivity analysis. Results: MR analysis indicated no significant causal relationship between PTSD and AIT (OR 0.920, 95% CI 0.832 to 1.017, p = 0.103), but a potential increase in the risk of GD associated with PTSD (OR 1.056, 95% CI 1.008 to 1.105, p = 0.021). MR-Egger intercept showed no horizontal pleiotropy (p > 0.05), and Cochran's Q showed no heterogeneity (p > 0.05). Sensitivity analysis suggested the MR results were robust. Conclusions: Evidence of an MR association between genetic liability to PTSD and an increased risk of GD were provided, but no evidence of association between PTSD and AIT. The findings indicate that individuals with PTSD may have an increased likelihood of developing GD, underscoring the importance of further research to comprehend the intricate interplay between PTSD and thyroid disorders. [ABSTRACT FROM AUTHOR]

Background: Among environmental factors, infectious agents, including Helicobacter pylori, can act as triggers for autoimmune thyroid diseases. Therefore, this study aimed to investigate the correlation between autoimmune Hashimoto's thyroiditis with H. pylori infection. Methods: The participants in this case-control study were 74 individuals 17-62 years who were divided into two groups, including 38 diagnosed Hashimoto's thyroiditis patients from an outpatient clinic of endocrinology and 36 apparently healthy individuals that were selected from family members of cases group age-matched and sex-matched. For individuals in two groups, a questionnaire was completed, including demographic information. Then, they were referred to the laboratory for thyroid stimulating hormone (TSH) and free T4 (FT4) in the control group and anti-thyroid peroxidase antibody (TPO-Ab) levels measurement in case and control groups. Stool samples were obtained from all individuals for H. pylori antigen detection using the ELIZA kit. Results: There was no significant difference in the mean age of case and control groups (P = 0.96), and 81.1% of individuals were female. 58.6% of patients with Hashimoto's thyroiditis and 41.4% of the control group had positive H. pylori, but there was no statistically significant difference between the two groups (P = 0.34). Furthermore, there was a significant positive correlation between TPO-Ab levels and H. pylori infection (r = 0.2, P = 0.03). Conclusion: TPO-Ab levels were associated with H. pylori infection diagnosed by H. pylori antigen. [ABSTRACT FROM AUTHOR]

Context: Fine-needle aspiration cytology (FNAC) is widely utilized for thyroid lesion diagnosis but faces challenges such as sample inadequacy and overlapping cytological features. This study examines how accurately these patterns correlate with histopathological diagnoses, shedding light on FNAC's limitations and diagnostic potential. Aims: To study the application of the architectural pattern of follicular cells in the interpretation of thyroid lesions and to demonstrate the diagnostic accuracy (DA) of FNAC. Settings and Design: Cross-sectional study carried over 1 year. Subjects and Methods: A total of 110 cases were reviewed by the cytopathologists. The prominent follicular cell architecture, namely macrofollicular, microfollicular, papillary, trabecular, three-dimensional clusters, and dispersed cells, was described in each case. In addition to these patterns, cellular morphology and background features were also noted, and a final cytological diagnosis was established. The cytology diagnosis was correlated with the histopathological diagnosis. Statistical Analysis Used: Sensitivity, specificity, positive predictive value, negative predictive value, DA of FNAC in diagnosing nonneoplastic and neoplastic lesions. Results: Macrofollicular pattern was seen in 80.26% of colloid goiter cases. Microfollicular pattern was observed in 72.2% of follicular neoplasm. About 62.5% of papillary thyroid carcinomas showed a papillary pattern. The trabecular pattern was seen in 42.86% of chronic lymphocytic thyroiditis and 16.67% of follicular neoplasms. The sensitivity and specificity of FNAC in diagnosing neoplastic lesions was 92.59% and 97.59%, respectively. Conclusions: FNAC is a simple, rapid, definite, and cost-effective primary diagnostic tool for thyroid evaluation. Cell architecture pattern is a simple and appropriate approach that complements cell morphology and background details in arriving at the final cytological diagnosis of thyroid lesions. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is the most common cause of goiter and acquired hypothyroidism in children after iodine deficiency. In this study, clinical and laboratory findings and follow-up results of children diagnosed with HT are presented. Methods: The data of cases diagnosed with HT between 2004 and 2022 in 2 centers in Erzurum were evaluated retrospectively. Results: Of the 81 children with HT whose ages ranged from 3 to 18 years (11.24 ± 3.72), 67 (82.7%) were girls and 14 (17.3%) were boys. The most common symptoms were neck swelling (37%), fatigue (23.5%), and hair loss (23.5%). There was a family history of HT in 12 cases (9.9%). Fifty-one (63%) of the cases were in the pubertal period and 30 (37%) were in the prepubertal period. There was no goiter in 36 (44.4%) of the patients, second degree goiter in 24 (29.6%), first degree goiter in 14 (17.3%), and third degree goiter in 7 (8.7%). Twenty-two (27.2%) of the cases were euthyroid, 27 (33.3%) were subclinical hypothyroidism, 23 (28.4%) were hypothyroidism, and 9 (11.1%) were hyperthyroidism. While 18 (22.2%) of the cases were followed up without medication, 59 (72.8%) were given levothyroxine and 4 (5%) were given methimazole. The mean follow-up time was 32.1 ± 33.7 months. Conclusion: The study's findings suggest that HT is more common in girls and occurs more frequently after puberty. A personal or family history of an autoimmune disease may be a warning sign for HT Additionally HT should be kept in mind in the differential diagnosis of children presenting with complaints of neck swelling, fatigue, and hair loss. [ABSTRACT FROM AUTHOR]

Background: Observational studies have suggested a correlation between alopecia areata (AA) and thyroid dysfunction (TD). However, the causal relationship between AA and TD remains uncertain. The purpose of this study is to investigate the causal relationship between these two conditions. Understanding the potential causal relationship between AA and TD is valuable for elucidating the pathogenesis of AA and for designing innovative methods to prevent and treat AA and its related complications. Methods: All data for this two‐sample Mendelian randomization (MR) study were sourced from public databases. This study selected hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, and Graves' disease as exposure factors, with AA as the outcome variable. Data for hypothyroidism, Hashimoto's thyroiditis, hyperthyroidism, subacute thyroiditis, Graves' disease, and AA were obtained from related genome‐wide association studies (GWAS). Various MR analysis methods such as inverse variance weighted (IVW), MR‐Egger, and weighted median were utilized. Additionally, Cochrane's Q test was used to detect heterogeneity in MR results, and the MR‐Egger intercept test and MR pleiotropy residual sum and outlier (MR‐PRESSO) test were used to detect horizontal pleiotropy. A leave‐one‐out analysis was conducted to investigate the sensitivity of this association. Results: We found statistically significant genetic predictions of AA with hypothyroidism, Hashimoto's thyroiditis, and subacute thyroiditis (IVW OR = 1.4009815, 95% confidence interval [CI]: 1.1210399–1.750829; p = 0.003030698, OR = 1.396101, 95% CI: 1.030134–1.89208; p = 0.03144273, OR = 0.732702, 95% CI: 0.604812–0.887634; p = 0.001483368). Furthermore, tests for pleiotropy showed no evidence of pleiotropy, enhancing the credibility of the study results. Finally, the leave‐one‐out test demonstrated the stability and robustness of this association. Conclusion: This study provides new evidence of a potential genetic link between thyroid issues and AA. By employing the two‐sample MR method to eliminate confounding factors and reverse causation, unbiased results were obtained, confirming a causal relationship between hypothyroidism, Hashimoto's thyroiditis, subacute thyroiditis, and AA. This lays the foundation for further mechanistic studies and potential clinical applications. Future research should further explore the specific biological mechanisms between TD and the onset of AA. [ABSTRACT FROM AUTHOR]

Background: Thyroid lesions may be developmental, inflammatory, hyperplastic and neoplastic.[2] Thyroid gland lesions vary in incidence in relation to the geographical area, age, sex, dietary and environmental factors. The aim of this study is to determine the spectrum of thyroid lesions. Study design: It is a descriptive type of retrospective study conducted at department of pathology at MGM medical college and hospital, Aurangabad. Methods and Material: 175 cases were included over a period of Five year from 1st January 2019-December 2023. All histopathological reports of thyroid specimens are retrieved from the record registers of department of pathology. The collected data will be entered in Microsoft Excel and analysed using SPSS version 24.0. Analysis of diagnosis done with parameters such as age and sex, nonneoplastic and neoplastic lesions. Grouping of these tumours will be done using the International Classification of World Health Organization (2018) accordingly. Also, data represented in form of visual impression like bar-diagram, pie diagram. Results: 175 specimens in total were studied. Female preponderance (80.57%) was noted. Commonest age group affected was in 41-50 years. The youngest was 8 years old and the oldest patients affected was 85 years. Thyroidectomy specimens were analysed on morphological basis which showed 68 % as nonneoplastic, 22.85% as neoplastic lesions and 9.14 % shows mixed lesions (neoplastic lesions co-existing with non-neoplastic conditions). Among all 175 cases, 55 cases shows multinodular goitre, 49 cases shows colloid goitre, 35 cases of Hashimoto's thyroiditis, 25 cases of Adenomatoid hyperplasia, 6 cases of granulomatous thyroiditis, and 1 case of thyroglossal cyst. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to effective primary therapeutic approaches such as thyroidectomy and radioiodine (RAI) therapy. However, we are often required to indicate second-line treatments to eradicate the tumor properly. In these scenarios, molecular therapies are promising alternatives, especially if specifically targetable mutations are present. Many of these targetable gene alterations originate from gene fusions, which can be found using molecular diagnostics like next-generation sequencing (NGS). Nonetheless, molecular profiling is far from being a routine procedure in the initial phase of PTC diagnostics. As a result, the mutation status, except for BRAF V600E mutation, is not included in risk classification algorithms either. This study aims to provide a comprehensive analysis of fusion mutations in PTC and their associations with clinicopathological variables in order to underscore certain clinical settings when molecular diagnostics should be considered earlier, and to demonstrate yet unknown molecular–clinicopathological connections. We conducted a retrospective fusion mutation screening in formalin-fixed paraffin-embedded (FFPE) PTC tissue samples of 100 patients. After quality evaluation by an expert pathologist, RNA isolation was performed, and then NGS was applied to detect 23 relevant gene fusions in the tumor samples. Clinicopathological data were collected from medical and histological records. To obtain the most associations from the multivariate dataset, we used the d-correlation method for our principal component analysis (PCA). Further statistical analyses, including Chi-square tests and logistic regressions, were performed to identify additional significant correlations within certain subsets of the data. Fusion mutations were identified in 27% of the PTC samples, involving nine distinct genes: RET, NTRK3, CCDC6, ETV6, MET, ALK, NCOA4, EML4, and SQSTM1. RET and CCDC6 fusions were associated with type of thyroidectomy, RAI therapy, smaller tumor size, and history of Hashimoto's disease. NCOA4 fusion correlated with sex, multifocality, microcarcinoma character, history of goiter, and obstructive pulmonary disease. EML4 fusion was also linked with surgical procedure type and smaller tumor size, as well as the history of hypothyroidism. SQSTM1 fusion was associated with multifocality and a medical history of thyroid/parathyroid adenoma. NTRK3 and ETV6 fusions showed significant associations with Hashimoto's disease, and ETV6, also with endometriosis. Moreover, fusion mutations were linked to younger age at the time of diagnosis, particularly the fusion of ETV6. The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota (GM) plays a pivotal role in influencing various health outcomes, including immune-mediated conditions, but its potential association with autoimmune thyroid disease (AITD) remains underexplored. We aimed to investigate the potentially pathogenic or protective causal impacts of specific GM on two types of AITD, namely Graves' disease and Hashimoto's thyroiditis, and analyzed the mediating effect of 731 immune cell phenotypes. Methods: Leveraging pooled genome-wide association study (GWAS) data of 211 gut microbiota traits, 731 immune cell phenotypes, and two types of AITD (Hashimoto's thyroiditis and Graves' disease), we performed bidirectional Mendelian randomization (MR) analyses to explore the causal relationships between the GM and AITD. Subsequently, we employed a multivariable MR analysis to discover potential mediating immune cell traits. Additionally, sensitivity analyses were utilized to ensure the reliability of the outcomes. Results: Our analysis revealed that a total of 7 GM taxa were positively associated with AITD, and other 14 taxa showed a negative correlation with AITD. Furthermore, we identified several immune cell traits that mediated the effects of GM on AITD. Most notably, Actinobacteria (p) presented protective effects on Hashimoto's thyroiditis via CCR2 on myeloid Dendritic Cell (5.0%), and Bifidobacterium (g) showed facilitating effects on Graves' disease through CD39+ CD4+ T cell %CD4+ T cell (5.0%) and CD14 on CD33+ HLA DR+ CD14dim (12.2%). Conclusion: The current MR study provides evidence supporting the causal relationships between several specific GM taxa and AITD, and further identified potential mediating immunophenotypes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto's thyroiditis (HT). Methods: Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay. Results: Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4–148.3) pg/mL vs. 131.9 (44.8–236.3) pg/mL; p = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy. Conclusions: Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients. [ABSTRACT FROM AUTHOR]

Purpose: Papillary thyroid carcinoma (PTC) frequently coexists with Hashimoto's thyroiditis (HT), which poses challenges in detecting central lymph node metastasis (CLNM) and determining optimal surgical management. Our study aimed to identify the independent predictors for CLNM in PTC patients with HT and develop a comprehensive prediction model for individualized clinical decision-making. Patients and methods: In this retrospective study, a total of 242 consecutive PTC patients who underwent thyroid surgery and central lymph node dissection between February 2019 and December 2021 were included. 129 patients with HT were enrolled as the case group and 113 patients without HT as control. The results of patients' general information, laboratory examination, ultrasound features, pathological evaluation, and BRAF mutation were collected. Multivariate logistic regression analysis was used to identify independent predictors, and the prediction model and nomogram were developed for PTC patients with HT. The performance of the model was assessed using the receiver operating characteristic curve, calibration curve, decision curve analysis, and clinical impact curve. In addition, the impact of the factor BRAF mutation was further evaluated. Results: Multivariate analysis revealed that gender (OR = 8.341, P = 0.013, 95% CI: 1.572, 44.266), maximum diameter (OR = 0.316, P = 0.029, 95% CI: 0.113, 0.888), multifocality (OR = 3.238, P = 0.010, 95% CI: 1.319, 7.948), margin (OR = 2.750, P = 0.046, 95% CI: 1.020, 7.416), and thyrotropin receptor antibody (TR-Ab) (OR = 0.054, P = 0.003, 95% CI: 0.008, 0.374) were identified as independent predictors for CLNM in PTC patients with HT. The area under the curve of the model was 0.82, with accuracy, sensitivity, and specificity of 77.5%, 80.3% and 75.0%, respectively. Meanwhile, the model showed satisfactory performance in the internal validation. Moreover, the results revealed that BRAF mutation cannot further improve the efficacy of the prediction model. Conclusion: Male, maximum diameter > 10mm, multifocal tumors, irregular margin, and lower TR-Ab level have significant predictive value for CLNM in PTC patients with HT. Meanwhile, BRAF mutation may not have a valuable predictive role for CLNM in these cases. The nomogram constructed offers a convenient and valuable tool for clinicians to determine surgical decision and prognostication for patients. [ABSTRACT FROM AUTHOR]

Circulating tumor cell (CTC) has been used to assist in the diagnosis and progression assessment of solid tumors, but the relationship between preoperative CTCs levels and central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) needs to be clarified. Methods: Data on clinical features (age, gender, Hashimoto's thyroiditis, multifocal, maximum lesion diameter, invaded capsule, clinical stage, and status of lymph node metastasis) of PTC patients treated at our hospital between June 2021 and April 2023 were retrospectively collected. The relationship between the CTCs level and these clinical features was analyzed, especially the relationship between the CTCs level and CLNM. Results: A total of 705 PTC patients were included, and there were 333 (47.2%) patients with CLNM. Patients with a high CTCs level had higher proportions of multifocality, maximum lesion diameter > 1cm, and CLNM than those in patients with a low CTCs level. Tumor size was connected to CTCs level, patients with a high CTCs level had a higher proportion of CLNM than those with a low CTCs level in PTC with maximum lesion diameter ≤ 1cm (45.3% vs 29.7%) (p=0.001). Logistic regression analysis showed that age < 55 years old (odds ratio (OR): 2.612, 95% confidence interval (CI): 1.565– 4.361, p< 0.001), invaded capsule (OR: 1.662, 95% CI: 1.098– 2.517, p=0.016), and high CTCs level (≥ 8.7 FU/3mL, OR: 2.141, 95% CI: 1.431– 3.203, p< 0.001) were associated with CLNM in PTC with maximum lesion diameter ≤ 1cm. Conclusion: In PTC patients with maximum lesion diameter ≤ 1cm, patients with high preoperative CTCs level (≥ 8.7FU/3mL), age < 55 years old, and capsular invasion were prone to CLNM. However, similar results were not observed in patients with maximum lesion diameter > 1cm. [ABSTRACT FROM AUTHOR]

BACKGROUND. Latent autoimmune diabetes of adults (LADA) is a type of diabetes that develops after the age of 30 and has signs of type 1 and type 2 diabetes. Its feature is that the destruction of β-cells of the pancreas occurs more slowly and the patient can during do not need insulin therapy for a certain period of time. Autoimmune diseases are a class of diseases in which the immune system perceives its own cells as foreign and attacks them. Although LADA and autoimmune diseases are not directly related, research shows that people with LADA diabetes have an increased risk of developing other autoimmune diseases. OBJECTIVE. To familiarize with the clinical manifestations, aspects of diagnosis and treatment of LADA diabetes with the help of literary sources, as well as to investigate the relationship of LADA with other autoimmune diseases. MATERIALS AND METHODS. Object: LADA diabetes as an orphan disease and its relationship with other autoimmune diseases. Research method: a review of literary sources. RESULTS. The combination of LADA and autoimmune thyroiditis (AIT) is quite common: according to studies, 10-25 % of patients with LADA have AIT. The relationship between LADA and other autoimmune diseases such as rheumatoid arthritis, Sjögren's disease, peripheral T-cell lymphoma, and systemic lupus erythematosus was also revealed. The study of the microbiome is an interesting and promising direction, because there is a deep connection between the intestinal microbiota and the immune system, the dysregulation of which underlies many important diseases. CONCLUSIONS. Each patient with LADA has individual characteristics, which leaves an imprint on the prognosis of the disease and approaches to treatment. The main goal is to maintain a normal level of glucose in the blood to avoid complications. The combination of LADA diabetes with AIT is quite common (10-25 % of cases), so it is advisable for patients with LADA to undergo an examination to confirm or exclude AIT. The combination of LADA diabetes with other autoimmune diseases is quite rare, but it can affect the clinical course of the disease, worsen glycemic control, and require more intensive diabetes treatment.

Autoimmune thyroiditis (AIT) is a chronic thyroid disorder wherein overstimulated CD4+T lymphocytes activate CD8+ cytotoxic T lymphocytes, thereby inducing Fas-mediated apoptosis of thyrocytes and reducing the hormonal activity of the thyroid gland. Recent studies suggest that autophagy, a process vital for maintaining cellular homeostasis through the degradation of damaged proteins and organelles in autolysosomes, is involved in the pathogenesis of autoimmune diseases. This article examines autophagy in peripheral blood mononuclear cells and the expression of key autophagy proteins (Vps34, p62, and LC3) in patients with AIT. The number of autophagosomes in the cells was tracked and assessed using flow cytometry. The expression of the protein markers was measured by western blotting. It was demonstrated that the levels of Vps34, LC3-II, and p62 increased significantly in the lymphocytes of all patients with AIT. The high level of the autophagosome protein LC3-II correlated with that of the ubiquitin-binding protein p62, which may indicate a disruption in the late stage of autophagy, i.e., in the fusion of autophagosomes with lysosomes. Impaired autophagy promotes excessive accumulation of autophagosomes in the cytoplasm, which, in turn, triggers apoptotic or necrotic cell death. Therefore, understanding the mechanisms of impaired autophagy in lymphocytes could be a promising avenue for slowing and limiting the damage associated with the onset and development of AIT.

Background/Objectives: Diabetic ketoacidosis (DKA) is an acute and potentially life-threatening complication characterized by the accumulation of ketone bodies in the blood, primarily occurring in patients with type 1 diabetes and occasionally in those with type 2 diabetes under certain conditions. DKA presents with symptoms such as polyuria, polydipsia, polyphagia, and, in severe cases, mental status changes. Identifying the triggering factor is crucial to prevent complications and effectively manage this medical emergency. Methods: This report describes the case of a 58-year-old male patient with stage IIIb nodular melanoma, diagnosed in November 2022. Results: After receiving five cycles of pembrolizumab, the patient developed de novo DKA, presenting with blurred vision, asthenia, adynamia, polyuria, and polydipsia. He was admitted to the emergency department with a blood glucose level of 764 mg/dL, confirming hyperglycemia and metabolic acidosis. He was transferred to the intensive care unit for fluid resuscitation and insulin infusion. After adequate clinical evolution and meeting the criteria for DKA resolution, possible autoimmune endocrinopathies secondary to immunotherapy were considered. Due to this complication, the oncological treatment was changed. Finally, the patient was discharged with the need to continue insulin therapy and oral hypoglycemic agents, along with thyroid hormone supplementation. Conclusions: The novelty of this case lies in the presentation of DKA as an immune-mediated complication induced by pembrolizumab, highlighting the importance of closely monitoring patients receiving immune checkpoint inhibitors to detect and manage emerging autoimmune endocrinopathies. It is essential to adjust oncological treatment according to the patient’s response and promptly manage autoimmune endocrinopathies to improve clinical outcomes and the patient’s quality of life.

Background. Violation of the integrity of the histohematologic barriers (blood-brain, blood-testis, blood-ocular, blood-labyrinth, blood-thyroid) leads to autoimmune damage to these organs. One of the manifestations of the latter is autoimmune thyroiditis, the structural and quantitative changes of which can be more informatively accurately assessed by polarization biomedical optics. The purpose of the study was to substantiate the possibility of using polarization biomedical optics methods in the diagnosis of autoimmune thyroiditis based on the use of pathophysiological analysis of blood-brain barrier integrity disorders. Materials and methods. Two groups of patients were studied: control group 1 — healthy donors (n = 51), study group 2 — people with autoimmune thyroiditis (n = 51) who underwent a puncture biopsy of the thyroid gland for diagnostic purposes. Instrumental laser methods were used: polarization, interference, multifractal. The statistical parameters of polarization ellipticity maps, polarization ellipticity of phase and multifractal spectra of digital microscopic images of native thyroid histological sections in patients with autoimmune thyroiditis were quantified: mean, dispersion, asymmetry, and kurtosis. The probability of differences compared to the controls, taken as 100 %, was evaluated using the Student’s parametric test (p

The aim of the study was to find out the pattern of IgM and IgG changes in patients with autoimmune thyroiditis depending on the pathological process duration. Materials and methods. A single-center cross-sectional study with randomization elements enrolled 170 patients with autoimmune thyroiditis, and 65 patients without thyroid pathology or other autoimmune diseases were assigned to sex- and age-matched comparison group (p = 0.6155 and p = 0.3093, respectively). The patients were classified according to thyroid status parameters into subclinical and manifest groups. All study participants were examined on IgM and IgG levels based not only on the clinical form of the disease, but also on the disease duration (up to 5 years and more than 5 years). The control group comprised 65 healthy individuals, including 26 men and 39 women (mean age 38.7 ± 10.8 years). Results. A slight decrease in IgM levels was observed in patients with subclinical form and longer disease duration, which was 1.5 (1.5; 1.7) g/l with the disease duration of up to 5 years and 1.4 (1.2; 1.4) g/l with the disease duration of more than 5 years, while there were no differences in IgM levels in patients with manifest form with longer disease duration. IgG concentrations were statistically significantly higher in both clinical groups of patients with the disease duration of up to 5 years compared to those in patients with the disease duration of more than 5 years (13 (11; 14) g/l up to 5 years and 11 (10; 12) g/l more than 5 years in subclinical group, p < 0.05); 13 (12; 14) g/l up to 5 years and 12 (10; 15) g/l more than 5 years in manifest group, p < 0.05). Conclusions. A downward trend in IgG concentrations is noted with the disease progression and longer duration, while IgM levels are uninformative.

The review focuses on the discussion of the role of selenium in the thyroid hormone metabolism and its impact on the risk of thyroid disorders, among which the most common are autoimmune thyroiditis (Hashimoto's disease) and Graves' disease. Selenium, which is a component of selenoproteins, such as glutathione peroxidase and iodothyronine deiodinases, is involved in the thyroid hormone synthesis and regulation and has an antioxidant effect on thyrocytes. Selenium deficiency can contribute to the development of thyroid disorders, aggravating the inflammatory processes and increasing the levels of antibodies against thyroid peroxidase (TPO AB) and thyroglobulin (TG AB). Clinical trials show that selenium supplements can reduce the levels of thyroid autoantibodies in patients with autoimmune thyroiditis, thereby improving the thyroid structure and reducing inflammation. In patients with Graves' disease, selenium supplements demonstrate a positive effect on the ophthalmopathy progression and quality of life. However, the effect of selenium varies depending on the mineral baseline levels, which emphasizes the need for individual approach to treatment. The literature review shows an important role of selenium in maintaining health of the thyroid gland and emphasizes the need for further research aimed to optimize therapy based on the selenium supplementation.

Background. Autoimmune thyroid diseases (AITDs), which include diffuse toxic goiter (DTG), or Graves’ disease, and autoimmune thyroiditis (AIT), are the most common organ-speci­fic autoimmune diseases. Since recently the population of Ukraine is in a state of chronic stress associated with military operations on the territory of our country, it is important to clarify the nature of stress impact on cellular immunity in patients with autoimmune thyroid pathology. The purpose of the study was to establish the features of the cellular link of the immune response to stress in patients with autoimmune thyroiditis and diffuse toxic goiter. Materials and me­thods. Sixty patients with AITDs were examined in the clinic of V. Danilevsky Institute for Endocrine Pathology Problems of the National Academy of Medical Sciences of Ukraine, 32 patients with AIT and 28 with DTG. In 24 cases, AITDs were newly diagnosed during the armed conflict (12 patients with DTG and 12 patients with AIT), and in 36 cases, the disease had a long course (16 patients with DTG and 20 patients with AIT, the manifestation took place until 2022). The relative (%) levels of CD3, CD4, CD8, CD16 and CD22 were determined in order to characterize immune homeostasis in patients with AITDs. Immunoregulatory indices were calculated as integral criteria of regulatory and effector links of immunity: suppression — CD4/CD8 as one of the key indicators of immune status, as well as indices of B cell help — CD4/CD16 and CD8/CD16. Results. The presence of DTG newly diagnosed in wartime is accompanied by a significant decrease in CD3 compared to the long-term course (55.67 ± 1.08 vs. 59.12 ± 1.14, P

Takayasu arteritis (TA), also known as “pulseless disease,” is a chronic large vessel vasculitis of unknown etiology that predominantly involves the aorta and its major branches. TA occurs worldwide and can affect all ethnic groups; the disease is most common in Asians. In this case report, we present a case of 15-year-old female, with a history of autoimmune thyroiditis presented with transient ischemic attack, the absence of peripheral and feeble central pulses with bruits that could be heard along the carotid, renal, and abdominal arteries, and a difference of > 10 mmHg in systolic blood pressure between arms. She was diagnosed clinically with TA. Digital subtraction angiography revealed aortoarteritis with involvement of bilateral subclavian, left proximal common carotid artery, and abdominal aorta. The patient was started on high-dose corticosteroid and methotrexate but due to steroid toxicity shifted to injection tocilizumab. She is on treatment and asymptomatic.