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13 pages, 1164 KB  
Systematic Review
Myo-Inositol Plus Selenium vs. Selenium Alone in Hashimoto’s Thyroiditis with Subclinical Hypothyroidism: A Systematic Review and Updated Meta-Analysis with Trial Sequential Analysis
by Pavel Stanchev, Maria Kraeva, Petar-Preslav Petrov and Plamen Penchev
J. Clin. Med. 2026, 15(9), 3179; https://doi.org/10.3390/jcm15093179 - 22 Apr 2026
Viewed by 180
Abstract
Introduction: Hashimoto’s thyroiditis (HT) is the leading cause of hypothyroidism in iodine-sufficient regions and often presents with subclinical hypothyroidism. Selenium (Sel) has immunomodulatory effects, while myo-inositol (MI) may enhance thyroid-stimulating hormone (TSH) signaling. This study evaluated whether adding myo-inositol to selenium provides [...] Read more.
Introduction: Hashimoto’s thyroiditis (HT) is the leading cause of hypothyroidism in iodine-sufficient regions and often presents with subclinical hypothyroidism. Selenium (Sel) has immunomodulatory effects, while myo-inositol (MI) may enhance thyroid-stimulating hormone (TSH) signaling. This study evaluated whether adding myo-inositol to selenium provides additional benefit compared with selenium alone in these patients. Methods: A systematic search of PubMed, Web of Science, and the Cochrane Library was conducted from inception to 7 March 2026. Studies comparing myo-inositol plus selenium (MI + Sel) with Sel monotherapy were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a frequentist random-effects model. Outcomes of interest included TSH, free T3 and T4, thyroglobulin antibodies (TgAb), and thyroid peroxidase antibodies (TPOAb). Trial sequential analysis (TSA) was performed to assess the robustness of significant findings. Results: Three studies involving 288 patients were included (151 receiving MI + Sel and 137 receiving Sel alone). Combination therapy significantly reduced TSH levels compared with Sel monotherapy (SMD −1.26; 95% CI −1.51 to −1.00; p < 0.01; I2 = 0%), and TSA suggested that this finding may be robust, although the evidence is limited by the small number of studies. TgAb levels were also significantly reduced (SMD −0.51; 95% CI −0.78 to −0.24; p < 0.01; I2 = 0%); however, TSA indicated a potential risk of type I error. No significant differences were observed for T3 (SMD 0.15; 95% CI −0.09 to 0.38; p = 0.22; I2 = 7%), T4 (SMD −0.01; 95% CI −0.72 to 0.69; p = 0.97; I2 = 88%), or TPOAb (SMD −0.18; 95% CI −0.44 to 0.09; p = 0.20; I2 = 0%). Conclusions: MI combined with Sel was associated with a significant reduction in TSH levels compared with Sel alone in patients with HT and subclinical hypothyroidism, suggesting a potential therapeutic benefit. However, given the limited number of studies, these findings should be interpreted with caution. Further large randomized controlled trials are required to confirm the effects on thyroid function and autoimmunity. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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10 pages, 1953 KB  
Article
The Role of Thyroid Elastography in Children with Type 1 Diabetes Mellitus or Celiac Disease Who Have Negative Thyroid Autoantibodies
by Arzu Gülseren, Serkan Bilge Koca, Tuğba Uylar Seber, Esra Eren and Buket Daldaban Sarıca
J. Clin. Med. 2026, 15(8), 2840; https://doi.org/10.3390/jcm15082840 - 9 Apr 2026
Viewed by 241
Abstract
Background/Objectives: Autoimmune thyroiditis affects physical and cognitive development in children. Therefore, early detection can prevent symptoms that could lead to lifelong changes. Autoimmune thyroiditis can frequently accompany type 1 diabetes (T1DM) and celiac disease (CD). The goal in this study is to [...] Read more.
Background/Objectives: Autoimmune thyroiditis affects physical and cognitive development in children. Therefore, early detection can prevent symptoms that could lead to lifelong changes. Autoimmune thyroiditis can frequently accompany type 1 diabetes (T1DM) and celiac disease (CD). The goal in this study is to evaluate its usability as a screening method by assessing thyroid elasticity in children with negative thyroid autoantibodies and T1DM or CD. Methods: This cross-sectional, case–control, single-center study was conducted with children who had applied to the Pediatrics outpatient clinic of Kayseri City Education and Research Hospital (Turkey). The study included three groups of cases (T1DM, CD and control). The value of the shear wave elastography (SWE) color map was recorded in kPa. Comparisons between two independent groups were conducted using either Student’s t-test or the Mann–Whitney U-test, while categorical variables were analyzed with the Chi-square test. A correlation analysis was conducted to evaluate the relationship between the variables. Results: The study cohort comprised 185 children, of whom 71 had T1DM, 54 had CD, and 60 constituted the healthy control group. The participants ranged in age from 4 to 17.9 years, with a mean age of 11.4 ± 3.8 years. The gender distribution did not differ significantly between the groups. Anti-thyroid peroxidase (TPOAb) levels did not differ significantly between the groups (p = 0.894). Thyroid volume or standard deviation score did not differ significantly between the groups. Corresponding SWE values in the T1DM, CD and control groups were 7.7 (6.0–9.3), 5.9 (5.2–7.9) versus 7.1 (6.0–9.6), respectively (p = 0.002). Correlations were significantly associated between SWE scores and anti-thyroglobulin (TgAb), thyroid volume, mean hemoglobin A1c (HbA1c), and time elapsed from a diagnosis of CD. Conclusions: The SWE scores were observed to be higher in children with T1DM compared to those with CD. Full article
(This article belongs to the Section Clinical Pediatrics)
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37 pages, 499 KB  
Review
The Role of Selenium in the Antioxidant System of Cattle, Pigs, and Small Ruminants: Implications for Animal Health and Productivity
by Katarzyna Żarczyńska, Katarzyna Różańska, Oliwia Świerczek and Dawid Tobolski
Animals 2026, 16(7), 1019; https://doi.org/10.3390/ani16071019 - 26 Mar 2026
Viewed by 663
Abstract
Oxidative stress contributes to reproductive disorders, immune dysfunction, and reduced productivity in livestock during periods of high metabolic demand and environmental challenge. Selenium supports antioxidant defense systems because it is incorporated as selenocysteine into selenoproteins, including glutathione peroxidases and thioredoxin reductases that detoxify [...] Read more.
Oxidative stress contributes to reproductive disorders, immune dysfunction, and reduced productivity in livestock during periods of high metabolic demand and environmental challenge. Selenium supports antioxidant defense systems because it is incorporated as selenocysteine into selenoproteins, including glutathione peroxidases and thioredoxin reductases that detoxify peroxides and sustain redox balance. The review summarizes selenium occurrence and chemical forms in feeds, as well as its absorption, transportation, and storage. The review also outlines the major features of selenoprotein biosynthesis and its prioritized allocation, with an emphasis on cattle, pigs, sheep, and goats. Evidence from multiple sources indicates that selenium status and supplementation interacts with antioxidant capacity, immune competence, thyroid hormone metabolism, reproductive performance, and the transfer of selenium to milk and offspring. In ruminants, rumen microbial transformations can reduce the bioavailability of inorganic selenium salts, and organic sources, such as selenium-enriched yeast, hydroxy-selenomethionine, and selenitetriglycerides, often increase blood and milk selenium more effectively. In pigs, organic selenium is commonly associated with enhanced antioxidant and immune indices in sows and piglets during late gestation, lactation, and weaning, whereas effects on growth performance are inconsistent. The review emphasizes the narrow margin between adequacy and excess and outlines practical considerations for supplementation and monitoring, alongside research needs for emerging selenium forms and functional biomarkers. Full article
14 pages, 915 KB  
Article
Serum Cocaine- and Amphetamine-Regulated Transcript (CART) Levels in Graves’ Disease: Associations with Metabolic Status, Autoimmunity, and Thyroid Ultrasound Heterogeneity
by Betül Çiğdem Yortanlı, Ümmügülsüm Can, İslam Köse, Semiha Durmaz, Mehmet Yortanlı and Oğuzhan Aksu
Int. J. Mol. Sci. 2026, 27(5), 2428; https://doi.org/10.3390/ijms27052428 - 6 Mar 2026
Viewed by 408
Abstract
Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism and a hypermetabolic state involving complex endocrine, metabolic, and immune interactions. Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide involved in energy balance, neuroendocrine signaling, and neuroimmune modulation; however, its circulating levels and [...] Read more.
Graves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism and a hypermetabolic state involving complex endocrine, metabolic, and immune interactions. Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide involved in energy balance, neuroendocrine signaling, and neuroimmune modulation; however, its circulating levels and clinical relevance in GD remain unclear. In this single-center prospective study, serum CART levels were evaluated in 44 patients with GD and 44 age- and sex-matched healthy controls. Associations with thyroid function, autoimmune markers, metabolic parameters, and thyroid ultrasound heterogeneity were analyzed. Serum CART concentrations were measured using an enzyme-linked immunosorbent assay, and clinical, biochemical, and ultrasonographic data were recorded. Serum CART levels did not differ significantly between GD patients and healthy controls. However, within the GD group, CART levels varied significantly according to thyroid ultrasound heterogeneity, with lower levels observed in patients with severe parenchymal heterogeneity. Serum CART levels showed positive correlations with body mass index and insulin resistance indices, while inverse correlations were observed with thyrotropin receptor antibody and anti-thyroid peroxidase antibody levels. No significant associations were identified between serum CART levels and circulating thyroid hormone concentrations. These findings suggest that serum CART may reflect metabolic and autoimmune heterogeneity rather than hypothalamic–pituitary–thyroid axis activity in GD, supporting its role as a context-sensitive, hypothesis-generating biomarker. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Targeted Regulation of Autoimmune Diseases)
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13 pages, 1289 KB  
Article
Part 1: The Role of Thyroglobulin Antibodies in Thyroid Cancer Development and Aggressiveness
by Rodis D. Paparodis, Evangelos Karvounis, George Simeakis, Ioannis Androulakis, Dimitrios P. Askitis, Sarantis Livadas, Andreas Rizoulis, Vasileios Papanikos, Nicholas S. Mastronikolis, Dimitra Zianni, Charalampos Massouras, Ilias Perogamvros, Anastasios Boniakos, Nicholas G. Angelopoulos, Dimitra Bantouna, Aikaterini Kapezanou, Ourania Aporelli and Juan Carlos Jaume
Cancers 2026, 18(5), 790; https://doi.org/10.3390/cancers18050790 - 28 Feb 2026
Viewed by 616
Abstract
Introduction: Thyroglobulin antibodies (Tg-Abs) are often thought to be associated with thyroid autoimmunity, and as such, a link with thyroid cancer has been found in some, but not all, studies. Tg-Abs are also found in non-autoimmune thyroid-follicular destruction. Given these contradictory results, we [...] Read more.
Introduction: Thyroglobulin antibodies (Tg-Abs) are often thought to be associated with thyroid autoimmunity, and as such, a link with thyroid cancer has been found in some, but not all, studies. Tg-Abs are also found in non-autoimmune thyroid-follicular destruction. Given these contradictory results, we designed the present study. Methods: We reviewed data from patients undergoing thyroidectomy for different indications in multiple centers across Greece and the US over 10 years. We compared the incidence of thyroid cancer and its features of tumor aggressiveness among patients with positive (≥30 IU/mL) and negative (<30 IU/mL) Tg-Abs titers and the Tg-Abs titers among patients with cancer, benign disease, and those with and without features of tumor aggressiveness. Furthermore, we performed multivariate and multiple regression analyses to identify if these effects were independently statistically significant. Results: We reviewed n = 9463 consecutive thyroidectomies and included n = 2873 subjects in the present work: n = 1537 with thyroid cancer and n = 1336 with benign disease. The incidence of thyroid cancer was significantly higher in preoperative Tg-Abs+ subjects, n = 273/638 (57.2%), compared with Tg-Abs− subjects, n = 1063/2235 (52.4%), OR 1.21, p < 0.05. Tumor size was larger, and capsular invasion and lymph node involvement were significantly more common in Tg-Abs+ subjects. Mean Tg-Abs were higher in subjects with tumors with extrathyroidal extension, capsular invasion, and lymph node involvement. On regression, Tg-Abs positivity was not associated with thyroid cancer incidence or aggressiveness, though, with the important exception of lymph node involvement (p < 0.001). Conclusions: Elevated preoperative thyroglobulin-antibody titers do not seem to affect the likelihood of developing thyroid cancer, even though they seem to be a surrogate for lymph node metastasis (as opposed to thyroid peroxidase antibodies, TPO-Abs). Further work is needed to clarify the interplay of this immune response on thyroid cancer metastatic behavior. Full article
(This article belongs to the Section Tumor Microenvironment)
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14 pages, 1260 KB  
Article
Hepatitis C Virus Infection Induces Autoimmune Hypothyroidism with Potential Profound Metabolic Implications: A Cross-Sectional Study in a High-Prevalence Region
by Xiaoli Zhong, Waseem Abbas, Farman Ullah and Rafi Ullah
Metabolites 2026, 16(2), 104; https://doi.org/10.3390/metabo16020104 - 31 Jan 2026
Viewed by 649
Abstract
Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and [...] Read more.
Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 106 IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article
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14 pages, 495 KB  
Article
A New Hypothesis on the Etiology of Down Syndrome: The Role of Anti-Zona Pellucida Antibodies as an Age-Independent Factor
by Giuseppe Noia, Tina Pasciuto, Francesco Ria, Alfredo Pontecorvi, Monica Sacco, Emanuela Teveroni, Maurizio Genuardi, Francesca Mauro, Paolo Spina, Emilia Spina, Giada Castagna, Daniela Visconti, Antonio Lanzone and Marco De Santis
Int. J. Mol. Sci. 2026, 27(2), 991; https://doi.org/10.3390/ijms27020991 - 19 Jan 2026
Viewed by 679
Abstract
Down Syndrome (DS) is the most common chromosomal abnormality characterized by neurodevelopmental impairment. Apart from maternal age, its risk factors remain poorly understood. This prospective case-control study aimed to evaluate the role of maternal anti-zona pellucida (ZP) antibodies (Ab) and anti-thyroid-Ab in predicting [...] Read more.
Down Syndrome (DS) is the most common chromosomal abnormality characterized by neurodevelopmental impairment. Apart from maternal age, its risk factors remain poorly understood. This prospective case-control study aimed to evaluate the role of maternal anti-zona pellucida (ZP) antibodies (Ab) and anti-thyroid-Ab in predicting DS. Correlations of anti-ZP-Ab and anti-thyroid-Ab with maternal age were also assessed. Anti-ZP-Ab were measured after childbirth using ELISA. Anti-thyroid peroxidase (aTPO) and anti-thyroglobulin (aTgII) antibodies were also analysed with the Allelica IM platform. Statistical analyses included receiver operating characteristic curve assessment, expressed as area under the curve (AUC) and linear regression modeling. Between September 2020 and October 2022, 58 women were enrolled. Anti-ZP-Ab levels were significantly higher in women with DS pregnancy with an odds ratio adjusted for maternal age of 71.52 (95% CI: 7.05–725.18) and an excellent predictive performance (AUC = 0.94; 95% CI: 0.88–1.00). For optical density levels > 1, the accuracy was 89.7% (95% CI: 78.2–100.0). No statistically significant differences were observed for aTPO and aTgII. Neither Anti-ZP-Ab nor anti-thyroid antibodies increased with age. These findings suggest that Anti-ZP-Ab are strongly associated with DS risk, suggesting a potential age-independent autoimmune contribution to trisomy 21. Their evaluation may support preconception counseling, especially for women aged > 35 years. Future studies could clarify causality and define the role of maternal autoimmunity in DS etiology. Full article
(This article belongs to the Special Issue New Advances in Reproductive Immunology and Pathology)
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15 pages, 621 KB  
Article
Retinal Microvascular and Orbital Structural Alterations in Thyroid Eye Disease
by Vera Jelušić, Ivanka Maduna, Dubravka Biuk, Zdravka Krivdić Dupan, Josip Barać, Nikolina Šilješ, Laura Jelušić, Tvrtka Benašić and Jelena Juri Mandić
J. Clin. Med. 2026, 15(1), 323; https://doi.org/10.3390/jcm15010323 - 1 Jan 2026
Viewed by 718
Abstract
Background/Objectives: Thyroid eye disease (TED) can lead to structural and microvascular changes in the orbit and retina. This study aimed to investigate the associations between Clinical Activity Score (CAS), orbital magnetic resonance imaging (MRI) measurements, and retinal microvascular changes in TED patients. Methods [...] Read more.
Background/Objectives: Thyroid eye disease (TED) can lead to structural and microvascular changes in the orbit and retina. This study aimed to investigate the associations between Clinical Activity Score (CAS), orbital magnetic resonance imaging (MRI) measurements, and retinal microvascular changes in TED patients. Methods: This cross-sectional study included 38 patients (76 eyes) with TED. Each patient underwent a comprehensive ophthalmological evaluation, CAS assessment, and a detailed medical history. Optical coherence tomography angiography (OCTA) was performed to quantify vessel density (VD) in the superficial and deep capillary plexus (SCP and DCP). Exophthalmos, extraocular muscle thickness and orbital fat thickness were measured on MRI scans to evaluate structural changes. Laboratory analyses included thyroid hormone levels, thyrotropin receptor antibodies (TRAb), anti-thyroid peroxidase antibodies (anti-TPO), and lipid profile. Results: Active TED patients (CAS ≥ 3) had significantly higher TRAb levels (p < 0.001), while anti-TPO did not differ between groups. Active eyes showed significantly higher DCP VD in the whole image (p = 0.013), parafovea (p = 0.012), and perifovea (p = 0.009) across all quadrants, with no difference in SCP or the foveal avascular zone (FAZ). In linear mixed model regression analyses, after adjusting for previous glucocorticosteroid therapy, higher triglycerides, greater medial rectus thickness, and whole-image DCP VD independently predicted higher CAS values (R2 = 42, p < 0.001). After adjusting for age and sex, CAS remained significantly positive predictor of DCP VD in the parafovea (R2 = 0.22, p < 0.001). Conclusions: Changes in DCP VD reflect TED activity and structural orbital involvement. Full article
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15 pages, 3702 KB  
Case Report
Idiopathic Hypertrophic Pachymeningitis with Elevated Anti-Thyroglobulin Antibodies—A Case Report
by Paweł Pobudejski, Mateusz Toś, Katarzyna Zawiślak-Fornagiel and Joanna Siuda
Reports 2026, 9(1), 15; https://doi.org/10.3390/reports9010015 - 31 Dec 2025
Viewed by 721
Abstract
Background and clinical significance: Idiopathic hypertrophic pachymeningitis (IHPM) is a rare inflammatory disorder characterized by diffuse or focal dural thickening and heterogeneous presentations. We report a corticosteroid-responsive IHPM with elevated anti-thyroglobulin (anti-Tg) antibodies despite oncologic control after thyroidectomy. This case suggests that [...] Read more.
Background and clinical significance: Idiopathic hypertrophic pachymeningitis (IHPM) is a rare inflammatory disorder characterized by diffuse or focal dural thickening and heterogeneous presentations. We report a corticosteroid-responsive IHPM with elevated anti-thyroglobulin (anti-Tg) antibodies despite oncologic control after thyroidectomy. This case suggests that systematic assessment for autoimmunity should be a standard component of the IHPM work-up. Case presentation: A 77-year-old woman presented with recurrent vertigo, imbalance, and headaches. Brain MRI showed diffuse pachymeningeal thickening with mild heterogeneous enhancement, radiologically stable over >2 years. Extensive evaluation excluded infectious, neoplastic (including paraneoplastic), cerebrospinal fluid hypotension and systemic autoimmune causes; findings did not support IgG4-related disease. Thyroid work-up revealed hypothyroidism with multinodular goiter; total thyroidectomy was performed, and there was no indication for adjuvant radioiodine therapy. Despite oncologic control, anti-Tg antibodies remained markedly elevated, while anti-thyroid peroxidase antibodies (anti-TPO) declined. Symptoms repeatedly improved with oral methylprednisolone and recurred on taper; adverse effects were mild and manageable. The patient remains under clinical and oncologic surveillance with symptom-guided steroid re-challenge. Conclusions: IHPM may exhibit a dissociation between clinical response and radiologic course. Persistently elevated anti-Tg after thyroidectomy can coexist with IHPM and may signal ongoing autoimmunity rather than active cancer. Full article
(This article belongs to the Section Neurology)
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27 pages, 1730 KB  
Article
Predicted T-Cell and B-Cell Epitopes of NIS: Where Do Sjögren’s Syndrome and Hashimoto’s Thyroiditis Converge?
by Rossella Talotta, Gabriele Cammaroto, Rosaria Maddalena Ruggeri, Elisa Postorino, Salvatore Cannavò and Pasquale Aragona
Int. J. Mol. Sci. 2026, 27(1), 200; https://doi.org/10.3390/ijms27010200 - 24 Dec 2025
Viewed by 903
Abstract
The sodium iodide symporter (NIS) is a key protein in thyroid function responsible for iodine uptake, and it may be involved in the pathogenesis of autoimmune thyroiditis. However, it is also expressed in the salivary glands, the primary target of autoreactive cells in [...] Read more.
The sodium iodide symporter (NIS) is a key protein in thyroid function responsible for iodine uptake, and it may be involved in the pathogenesis of autoimmune thyroiditis. However, it is also expressed in the salivary glands, the primary target of autoreactive cells in Sjögren’s syndrome (SS). Given the common link between the two diseases, we computationally investigated whether the epitopes of NIS can trigger an immune response leading to SS in Hashimoto’s thyroiditis (HT) patients genetically predisposed to both diseases. The TepiTool 2016, ABCpred 2006, and DiscoTope 2.0 servers were used to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of NIS, thyroid peroxidase (TPO) and Ro60 Y RNA-binding protein (Ro60), which served as reference antigens for HT and SS, respectively. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) alleles associated with both SS and HT. We identified a total of 376 linear T-cell epitopes, 64 linear B-cell epitopes and 68 conformational B-cell epitopes of NIS. Compared to TPO, NIS T-cell epitopes showed significantly lower affinity for HLA alleles (p < 0.0001), while no significant difference was found compared to Ro60. While linear B-cell epitopes of NIS, TPO, and Ro60 showed similar binding affinity, conformational epitopes of NIS were predicted to have higher immunogenicity than Ro60 (p = 0.04), while no significant difference was found compared to TPO. These pivotal findings, discovered by the methods of computer modeling, suggest that NIS can potentially activate T cells and B cells in patients with genetic predisposition to SS and HT and need to be confirmed by further laboratory studies. Full article
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18 pages, 447 KB  
Article
Integrative Analysis of Biochemical, Hormonal, and Histopathological Profiles in Thyroid Nodules: A Seven-Year Retrospective Study
by Sergiu-Ciprian Matei, Mervat Matei, Sorin Ursoniu, Anna Laura Maiozzi, Ana Silvia Corlan, Bianca Roxana Natarâş, Flavia Medana Petrașcu, Mihaela Maria Vlad, Diana Szekely, Flavia Zara and Cristina Stefania Dumitru
Biomedicines 2026, 14(1), 10; https://doi.org/10.3390/biomedicines14010010 - 20 Dec 2025
Viewed by 1502
Abstract
Background/Objectives: Thyroid nodules exhibit substantial histopathological variability, and systemic markers that differentiate benign from malignant patterns remain poorly defined. This study evaluated clinical, biochemical, hormonal, and histopathological characteristics in patients undergoing total thyroidectomy for nodular thyroid disease. Methods: A retrospective cohort [...] Read more.
Background/Objectives: Thyroid nodules exhibit substantial histopathological variability, and systemic markers that differentiate benign from malignant patterns remain poorly defined. This study evaluated clinical, biochemical, hormonal, and histopathological characteristics in patients undergoing total thyroidectomy for nodular thyroid disease. Methods: A retrospective cohort of 926 patients operated between 2017 and 2024 was analyzed. Patients were classified as: Group 1—benign lesions; Group 2—benign–malignant associations; Group 3—multiple malignant lesions. Demographic, biochemical, hormonal, and histopathological data were assessed using the Kruskal–Wallis and Mantel–Haenszel chi-square tests. Thyroid-specific tumor and autoimmunity markers (calcitonin, thyroglobulin, anti-thyroglobulin antibodies, and thyroid peroxidase antibodies) were not included in the comparative analyses due to their non-uniform availability across the retrospective cohort. Results: Most clinical and biochemical parameters showed no significant differences among the three groups, including TSH (p = 0.122), FT3 (p = 0.560), glycemia (p = 0.829), creatinine (p = 0.193), fibrinogen (p = 0.535), and thyroid dimensions (length p = 0.401, width p = 0.183, thickness p = 0.667, and total thyroid mass p = 0.109). Neutrophil count differed in the overall comparison (p = 0.021), although absolute differences were small, and lymphocyte counts were modestly lower in patients with multiple malignant lesions compared with benign disease (p = 0.009). Comorbidities and BMI were similarly distributed across groups (all p > 0.05). Overall, routinely available clinical, biochemical, and hormonal parameters demonstrated limited discriminatory value between patients with different histopathological patterns. Conclusions: Standard clinical, biochemical, and hormonal markers showed minimal ability to reflect underlying histopathological patterns in patients with thyroid nodules, underscoring their limited utility for preoperative risk stratification. Full article
(This article belongs to the Special Issue State-of-the-Art Endocrine Cancer Biology and Oncology)
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13 pages, 224 KB  
Article
Personalized Supplementation Is Associated with Reduced Inflammatory Biomarkers: A 12-Week Observational Study
by Eliza Roeth, Madeline Morris, Asher P. Reynolds, Emma M. Reynolds, Reed Hungerford, Eliza J. Livingston, Andrew W. Richardson, Benjamin T. Bikman and Paul R. Reynolds
Life 2025, 15(12), 1887; https://doi.org/10.3390/life15121887 - 10 Dec 2025
Viewed by 2165
Abstract
Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring [...] Read more.
Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring of systemic inflammation over time. We aimed to evaluate the impact of a 12-week personalized, biomarker-guided supplementation program including micronutrients, hormone support, and peptides on inflammatory and immune-related biomarkers across age- and sex-stratified adult cohorts. Participants (n = 48; 8 per group) were stratified by sex and age (40–49, 50–59, 60–69 years) and underwent blood testing at baseline and 12 weeks. Personalized protocols were developed based on individual biomarker profiles and included targeted interventions with vitamin D, omega-3 fatty acids, B vitamins, zinc, selenium, hormone optimization, and other supportive agents. Primary outcomes were percent changes in CRP, ferritin, homocysteine, WBC count, and anti-TPO antibody levels. CRP levels decreased by 33–46% across all groups, with similarly consistent declines in homocysteine (29–37%) and WBC count (22–28%). Ferritin reductions were most notable in men, particularly in older age groups (up to 48%), while anti-TPO antibody levels declined more prominently in women (up to 22%). These changes are consistent with reduced systemic inflammation, improved methylation status, and potential modulation of autoimmune activity. This biomarker-guided, personalized supplementation protocol was associated with clinically meaningful reductions in key markers of inflammation and immune dysregulation. These findings are suggestive of potential efficacy for precision-based health optimization programs and highlight the need for larger randomized controlled trials (RCTs) to confirm causal effects. Full article
16 pages, 1503 KB  
Systematic Review
Effect of Autoimmune Thyroid Disease on Pregnancy Outcomes: A Systematic Review and Meta-Analysis
by Anwar A. Sayed, Maryam Mohammed Abdulaal, Elaf Mohammed Emam, Laila Mohammed Daftardar, Razan Essam Kurdi, Yara Basim Alahmadi, Mayes Mohammed Alharbi and Razna Moustafa Aloufi
J. Clin. Med. 2025, 14(23), 8520; https://doi.org/10.3390/jcm14238520 - 1 Dec 2025
Cited by 2 | Viewed by 1696
Abstract
Background: Autoimmune thyroid disease (AITD) is common in women of reproductive age and is characterized by thyroid-specific autoantibodies, mainly TPOAbs and TgAbs. Its impact on pregnancy outcomes is not fully understood. However, evidence suggests a potential association with adverse maternal and neonatal outcomes. [...] Read more.
Background: Autoimmune thyroid disease (AITD) is common in women of reproductive age and is characterized by thyroid-specific autoantibodies, mainly TPOAbs and TgAbs. Its impact on pregnancy outcomes is not fully understood. However, evidence suggests a potential association with adverse maternal and neonatal outcomes. Objective: To assess the association between AITD and adverse pregnancy outcomes and evaluate the effect of levothyroxine (LT4) therapy in high-risk populations. Methods: A systematic search of PubMed and Web of Science was performed per PRISMA guidelines. Randomized controlled trials (RCTs) on pregnancy outcomes in women with AITD were included. Primary outcomes were preterm delivery, miscarriage, and live birth; secondary outcomes included maternal and neonatal complications. Risk of bias was assessed using RoB 2.0, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Eight RCTs with TPOAb-positive euthyroid or subclinical hypothyroid women were included. AITD increased preterm delivery risk (pooled OR 3.92, 95% CI 2.54–6.05). Miscarriage risk showed high heterogeneity (pooled OR 1.27, 95% CI 0.16–9.82). LT4 reduced miscarriage (pooled OR 0.52, 95% CI 0.34–0.80) and preterm delivery (pooled OR 0.37, 95% CI 0.17–0.80). Live birth rates favored LT4 but were not statistically significant. Maternal and neonatal complications were inconsistently reported. Conclusions: AITD is associated with higher preterm delivery risk. LT4 in high-risk women may reduce miscarriage and preterm birth. Further RCTs should stratify by AITD subtype, antibody titer, and thyroid function, and report perinatal outcomes systematically. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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16 pages, 1859 KB  
Article
Autoimmune Thyroid Disease and Female Fertility: Does Anti-TPO Accelerate Ovarian Aging?
by Sefa Arlıer and Sadık Kükrer
J. Clin. Med. 2025, 14(22), 8024; https://doi.org/10.3390/jcm14228024 - 12 Nov 2025
Viewed by 1731
Abstract
Background/Objectives: Thyroid autoimmunity, particularly anti-thyroid peroxidase antibodies (anti-TPO), has been implicated in reduced fertility and diminished ovarian reserve. However, the stratified effects of anti-TPO across age groups, body mass index (BMI) categories, and polycystic ovary syndrome (PCOS) status remain unclear. This study [...] Read more.
Background/Objectives: Thyroid autoimmunity, particularly anti-thyroid peroxidase antibodies (anti-TPO), has been implicated in reduced fertility and diminished ovarian reserve. However, the stratified effects of anti-TPO across age groups, body mass index (BMI) categories, and polycystic ovary syndrome (PCOS) status remain unclear. This study aims to investigate the association between anti-TPO positivity and ovarian reserve markers—antral follicle count (AFC), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH)—in euthyroid infertile women. Methods: This retrospective study included 1460 infertile women aged 18–45 years, evaluated between 2022 and 2025. Participants were categorized based on anti-TPO levels (≥9 vs. <9 IU/mL) using Beckman Coulter-DXI 800 analyzer, which uses chemiluminescent immunoassays to measure results. BMI (<30 vs. ≥30 kg/m2), and PCOS status. Age was categorized into five strata (18–25, 25–30, 30–35, 35–40, and 40–55 years), and <35 vs. ≥35 years. Linear regression models were used to assess the impact of anti-TPO on AMH and AFC within each subgroup. Additional logistic regression was performed to evaluate the odds of diminished ovarian reserve (DOR: AMH < 1 ng/mL or AFC < 5) after adjusting for age, BMI, and TSH. Results: Anti-TPO positivity (17.6% prevalence) was significantly associated with reduced AMH (1.47 ± 1.52 vs. 3.33 ± 3.03 ng/mL, p < 0.0001), reduced AFC (8.18 ± 5.06 vs. 15.88 ± 8.18, p < 0.0001), and elevated FSH (9.40 ± 6.21 vs. 8.06 ± 4.79 mIU/mL, p = 0.001). These associations remained significant in non-obese and PCOS-negative subgroups. Regression models revealed stronger associations in younger women (<35 years) and showed significant Anti-TPO × Age and Anti-TPO × BMI interactions. Logistic regression confirmed Anti-TPO ≥ 9 IU/mL as a strong predictor of diminished ovarian reserve (AMH < 1 ng/mL: OR = 3.13; AFC < 5: OR = 6.48). ROC analysis indicated modest predictive ability (AUC: 0.665–0.694), and path modeling confirmed direct effects of Anti-TPO on AMH and AFC independent of TSH or BMI. Conclusions: Elevated Anti-TPO levels are independently associated with diminished ovarian reserve in euthyroid women, particularly in younger, non-obese, and PCOS-negative individuals. Anti-TPO may serve as a useful biomarker in fertility risk assessment and personalized reproductive counseling, even in the absence of overt thyroid dysfunction. Full article
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23 pages, 2279 KB  
Review
Effects of Gluten-Free Diet in Non-Celiac Hashimoto’s Thyroiditis: A Systematic Review and Meta-Analysis
by Edilene Maria Queiroz Araújo, Claubert Radamés Oliveira Coutinho-Lima, André Silva de Sousa, Lana Mércia Santiago de Souza, Helton Estrela Ramos, Bianca de Almeida-Pititto, Graziela De Luca Canto and Virginia Fernandes Moça Trevisani
Nutrients 2025, 17(21), 3437; https://doi.org/10.3390/nu17213437 - 31 Oct 2025
Cited by 1 | Viewed by 8768
Abstract
Background/Objectives: The gluten-free diet (GFD) may be anti-inflammatory in treating Hashimoto’s thyroiditis (HT), but the studies are inconsistent. Methods: To determine the effects of the GFD in non-celiac HT, we included randomized controlled trials from the following databases: Cochrane Central, Embase, [...] Read more.
Background/Objectives: The gluten-free diet (GFD) may be anti-inflammatory in treating Hashimoto’s thyroiditis (HT), but the studies are inconsistent. Methods: To determine the effects of the GFD in non-celiac HT, we included randomized controlled trials from the following databases: Cochrane Central, Embase, Lilacs, Medline, Scopus, and Web of Science. The study was registered at Prospero (no. CRD42024566034). The outcomes assessed included free triiodothyronine (fT3), free tetraiodothyronine (fT4), thyroid stimulating hormone (TSH), Anti-thyroid Peroxidase (TPO), anti-thyroglobulin (Tg), C-reactive protein (CRP), body weight (BW), body mass index (BMI) and adverse effects. Sensitivity, subgroup, meta-regression, bias risk, and evidence analyses’ certainty were also assessed. Results: Only three studies were meta-analyzed, comprising 110 participants. The pooled data revealed the evidence was very uncertain about the effect of GFD compared to the control group on mean differences (MD) of TSH (MD −0.63 uIU/mL; 95% CI −1.63 to 0.36; p = 0.21), fT3 (MD −0.18 pg/mL; 95% CI −0.50 to 0.14; p = 0.28), fT4 (MD −0.33 ng/dL; 95% CI −0.89 to 0.23; p = 0.24), anti-Tg (MD −10.07 IU/mL; 95% CI −17.73 to −2.42; p = 0.010), anti-TPO (MD 76.19 IU/mL; 95% CI 46.86 to 108.51; p < 0.00001), CRP (MD −0.12 IU/mL; 95% CI −0.30 to 0.07), BW (MD −1.46 kg; 95% CI −6.70 to 3.77), and BMI (MD −1.80 kg/m2; 95% CI −3.30 to −0.31). The quality of evidence was rated as having serious methodological concerns to extremely serious imprecision. Conclusions: The GFD decreased anti-Tg and increased the anti-TPO levels, both significantly. There were no significant results on fT3, fT4, and TSH. Full article
(This article belongs to the Special Issue Effects of Diets and Nutrients on Immunity)
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