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10 pages, 417 KB  
Article
Thyroid Hormone Replacement Dose Is Not Associated with Anti-TPO and Anti-TG Antibody Titers in Hashimoto’s Disease
by Małgorzata Szczuko, Olimpia Szmigiel, Urszula Szczuko, Leon Rudak, Karolina Wrońska, Lidia Kwiatkowska, Małgorzata Tomasik, Anhelli Syrenicz and Jakub Pobłocki
J. Clin. Med. 2026, 15(3), 970; https://doi.org/10.3390/jcm15030970 (registering DOI) - 25 Jan 2026
Abstract
Background: Hashimoto’s thyroiditis (HT) is the result of a complex interplay between genetic, environmental, and epigenetic factors. The role of cellular and humoral immunity in the pathogenesis of the disease is well-established. Inflammatory infiltration of T and B lymphocytes is a key [...] Read more.
Background: Hashimoto’s thyroiditis (HT) is the result of a complex interplay between genetic, environmental, and epigenetic factors. The role of cellular and humoral immunity in the pathogenesis of the disease is well-established. Inflammatory infiltration of T and B lymphocytes is a key feature identified on ultrasound examination. The lack of data on the effect of L-thyroxine (LT-4) doses on the level of anti-TPO and anti-TG antibodies in Hashimoto’s thyroiditis and the relationship with anthropometric measurements resulted in the desire to fill this niche. Methods: A total of 70 Caucasian patients diagnosed with Hashimoto’s thyroiditis within the past two years were examined. The participants were divided into three groups based on their L-thyroxine dosage (≤50, 50–100, >100 μg). Results: The results revealed no correlation between the dosage of L-thyroxine and anthropometric measurements (age, height, body weight, and body fat content). No correlation was identified between the levels of anti-TPO and anti-TG and the dose of L-thyroxine in patients with Hashimoto’s thyroiditis. Conclusions: The mechanism regulating the levels of anti-TPO and anti-TG appears to be associated with a more advanced thyroid inflammation and disease process. Long-term observation of patients would be advisable. We present evidence of no effect of hormone dose on antibody levels in Hashimoto’s thyroiditis. Regardless of disease severity, immune regulation remains outside the scope of hormonal regulation. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment: 2nd Edition)
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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 139
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 318
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 360
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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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 930
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
14 pages, 510 KB  
Article
Linking Thyroid Function, Morphology, Autoimmunity, Body Mass Index, and Reproductive Aging to Women’s Sexual Health: Evidence from a Population Study in Kaunas
by Dalia Daukšienė, Raimonda Klimaitė, Aistė Kondrotienė, Radvilė Matukaitienė, Jonas Čeponis, Agnė Rimkutė, Laura Dudonytė, Rasa Steponavičiūtė, Dalia Lukšienė, Vaiva Lesauskaitė, Džilda Veličkienė, Rasa Verkauskienė and Birutė Žilaitienė
J. Clin. Med. 2025, 14(23), 8441; https://doi.org/10.3390/jcm14238441 - 28 Nov 2025
Viewed by 459
Abstract
Background/Objectives: While it is known that Hashimoto’s thyroiditis (HT), goiter, thyroid nodules, and thyroid dysfunction may affect women’s reproductive health through hormonal and metabolic mechanisms, data are limited regarding the specific impacts on female sexual function. This study evaluated sexual function in women [...] Read more.
Background/Objectives: While it is known that Hashimoto’s thyroiditis (HT), goiter, thyroid nodules, and thyroid dysfunction may affect women’s reproductive health through hormonal and metabolic mechanisms, data are limited regarding the specific impacts on female sexual function. This study evaluated sexual function in women with thyroid disorders and examined its associations with thyroid function, age, menopausal status, and body mass index (BMI). Methods: A population-based survey was conducted in Kaunas, Lithuania, within the WHO MONICA framework. A random sample of 1569 women aged 25–69 years was included in the final analysis after applying the exclusion criteria. Anthropometric measurements were taken using standardized procedures, and the BMI was calculated. Sexual function was assessed using the 19-item Female Sexual Function Index (FSFI). Thyroid structure was evaluated by a team of trained physicians using ultrasound, while thyroid function was assessed via serum analysis (ELISA-based assays for TSH, fT4, and anti-TPO antibodies). Results: Of the 1569 women analyzed, 64.1% had sexual dysfunction (SD) (FSFI ≤ 26.55). Age and BMI showed significant negative correlations with all FSFI domains, with the strongest associations for arousal, lubrication, and total FSFI score (p < 0.01). SD was more prevalent among postmenopausal (43.6%) women than in premenopausal women (22.6%, p < 0.001) and increased with a higher BMI (p < 0.001). HT was found in 28.3% of participants. Compared with the reference group, women with HT were older, had higher BMI, higher TSH levels, and more hypothyroidism (p < 0.001). SD was more common in the HT group (71.7% vs. 64.2%, p < 0.001), with significantly lower lubrication and higher pain scores. In the multivariate analysis, only goiter remained an independent predictor of SD (p = 0.04). Conclusions: In conclusion, women with HT were older; had a higher BMI; and more frequently experienced SD, particularly reduced lubrication and increased pain, compared with the reference group. Although several thyroid conditions were associated with sexual dysfunction, only goiter remained an independent predictor after adjusting for age and BMI. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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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 1149
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 5017
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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23 pages, 9119 KB  
Article
Protective Effects of Velvet Antler Polypeptides on Cyclophosphamide-Induced Myelosuppression in Mouse and Bone Marrow Mesenchymal Stem Cells
by Fusheng Gao, Yusu Wang, Jinze Liu, Yichen Xie, Ying Geng, Zhongmei He, Jianan Geng, Jianming Li, Weijia Chen and Rui Du
Nutrients 2025, 17(21), 3428; https://doi.org/10.3390/nu17213428 - 31 Oct 2025
Viewed by 1177
Abstract
Background: Myelosuppression is one of the most common chemotherapy side effects, seriously threatening the quality of life of cancer patients. Studies have shown that velvet antler polypeptides (VAPs) could enhance immunity and anti-aging and also have a hematopoietic-promoting effect. However, there are relatively [...] Read more.
Background: Myelosuppression is one of the most common chemotherapy side effects, seriously threatening the quality of life of cancer patients. Studies have shown that velvet antler polypeptides (VAPs) could enhance immunity and anti-aging and also have a hematopoietic-promoting effect. However, there are relatively few studies on the treatment of myelosuppression with VAPs, and the therapeutic mechanism remains unclear. Methods: This study employed both in vitro and in vivo models to explore the mechanism of VAPs against myelosuppression. In this study, the cyclophosphamide (CTX)-induced bone marrow mesenchymal stem cell (BMSC) injury model was used to evaluate the effects of VAPs on cell viability, apoptosis, reactive oxygen species activity, and protein expression. Furthermore, a CTX-induced myelosuppression mouse model was employed to evaluate peripheral blood counts, organ indices, femoral tissue histopathology, immunohistochemical expression of CD34, VEGF, and Notch1, and key proteins in the Notch1/PI3K/AKT pathway in vivo. Results: Our results showed that VAPs protected BMSCs from CTX-induced apoptosis, inhibited ROS production, and promoted the secretion of VEGF, TPO, and VCAM-1, thereby improving the bone marrow microenvironment. Furthermore, the results showed that VAPs improved the peripheral blood counts and bone marrow nucleated cell (BMNC) count in CTX-induced myelosuppression mice and ameliorated pathological injury of the spleen, thymus, and liver. VAPs inhibited the apoptosis of bone marrow cells, manifested by regulating the expression levels of proteins like PI3K/p-PI3K, AKT/p-AKT, Bcl-2, Bax, and Caspase-3. Simultaneously, it upregulated the expression of Notch1 and Hes1 proteins. The application of the PI3K inhibitor LY294002 and the Notch1 inhibitor DAPT demonstrated that the ameliorative effect of VAPs on myelosuppression was dependent on the activation of both the Notch1 and PI3K/AKT pathways. Conclusions: Our study indicates that VAPs may achieve treatment of myelosuppression by improving the hematopoietic microenvironment, inhibiting apoptosis of mouse bone marrow cells, and regulating the Notch1 and PI3K/AKT signaling pathways. Full article
(This article belongs to the Section Proteins and Amino Acids)
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14 pages, 930 KB  
Article
The Relationship Between Composite Inflammatory Indices and Dry Eye in Hashimoto’s Disease-Induced Hypothyroid Patients
by Asli Kirmaci Kabakci, Derya Cepni Cakir and Arzu Taskiran Comez
Biomedicines 2025, 13(11), 2675; https://doi.org/10.3390/biomedicines13112675 - 30 Oct 2025
Viewed by 741
Abstract
Background/Objectives: Hashimoto’s thyroiditis-induced hypothyroidism (HT–HypoT) is frequently accompanied by ocular surface complaints, but the role of systemic inflammatory markers in dry eye disease (DED) among these patients remains unclear. This study aimed to evaluate the relationship between composite inflammatory indices and the [...] Read more.
Background/Objectives: Hashimoto’s thyroiditis-induced hypothyroidism (HT–HypoT) is frequently accompanied by ocular surface complaints, but the role of systemic inflammatory markers in dry eye disease (DED) among these patients remains unclear. This study aimed to evaluate the relationship between composite inflammatory indices and the presence and severity of DED in patients with HT–HypoT. Methods: This retrospective study included 86 HT–HypoT patients and 43 DED controls without systemic comorbidities. DED diagnosis and severity were assessed using the Ocular Surface Disease Index (OSDI) and objective ocular surface tests. Laboratory parameters and composite inflammatory indices—including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), C-reactive protein-to-albumin ratio (CAR), and prognostic nutritional index (PNI)—were compared between groups. Results: DED was present in 44% of HT–HypoT patients. SIRI and CAR were higher in HT–HypoT patients with DED and increased with severity. Both indices independently predicted the presence and severity of DED and exhibited higher diagnostic performance than other inflammatory indices. Conclusions: In patients with HT–HypoT, SIRI and CAR provide additional diagnostic value for identifying the presence and severity of DED beyond that offered by traditional markers. These findings highlight the potential utility of routine blood-derived indices as adjunctive biomarkers in thyroid-related DED. Full article
(This article belongs to the Special Issue Recent Research on Dry Eye)
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26 pages, 982 KB  
Review
Vitamin D Receptor Polymorphisms and Immunological Effects of Vitamin D in Hashimoto’s Thyroiditis
by Mateusz Pakosiński, Martyna Żyła, Anna Kamieniak, Natalia Kluz and Paulina Gil-Kulik
Int. J. Mol. Sci. 2025, 26(21), 10576; https://doi.org/10.3390/ijms262110576 - 30 Oct 2025
Cited by 1 | Viewed by 1638
Abstract
Introduction: Vitamin D is involved in numerous processes and is obtained both exogenously and endogenously. Its active form is 1,25-dihydroxycholecalciferol, which exerts its biological effects via the vitamin D receptor (VDR). The main factors influencing VDR density are polymorphisms of the VDR gene, [...] Read more.
Introduction: Vitamin D is involved in numerous processes and is obtained both exogenously and endogenously. Its active form is 1,25-dihydroxycholecalciferol, which exerts its biological effects via the vitamin D receptor (VDR). The main factors influencing VDR density are polymorphisms of the VDR gene, which may affect, e.g., gene mRNA stability and also VDR gene expression. There are four main polymorphic sites within the gene, BsmI, ApaI, FokI and TaqI, and two polymorphisms related to the gene promoter: GATA and Cdx2. One of the functions of vitamin D is to modulate the immune system. It affects T lymphocytes, B lymphocytes and dendritic cells. Currently, vitamin D deficiency is a common global problem that is associated with an increased risk of autoimmune diseases, including Hashimoto’s thyroiditis. Numerous studies have demonstrated an association between low vitamin D levels and elevated thyroid-stimulating hormone (TSH) levels, and have also proven the existence of a negative correlation between vitamin D levels andanti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibody titers. Review objectives and a concise summary of the methodology: The review aims to analyze studies examining the relationship between specific VDR polymorphisms, vitamin D levels, and the development of various diseases, with a particular emphasis on Hashimoto’s thyroiditis. This review is based on original and review articles written in English published between March 2018–November 2024 searched primarily in the PubMed, and additionally in Google Scholar databases. A narrative review of the literature was conducted. Conclusions: The presence of specific VDR polymorphisms influences the effectiveness of vitamin D supplementation, but the role of supplementation in the prevention of autoimmune diseases has not been definitively confirmed. To date, studies have primarily involved relatively small groups of patients with significant population heterogeneity, with case–control investigations being the most common. Therefore, further research on larger, more homogeneous groups is recommended to achieve more standardized results. Additionally, the influence of epigenetic factors modulating VDR activity and its interactions with the environmental factors is also important. Full article
(This article belongs to the Special Issue MicroRNAs and mRNA in Human Health and Disease)
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19 pages, 852 KB  
Article
Probiotic Supplementation Enhances the Effects of a Nutritional Intervention on Quality of Life in Women with Hashimoto’s Thyroiditis—A Double-Blind Randomised Study
by Karolina Osowiecka, Damian Skrypnik and Joanna Myszkowska-Ryciak
Nutrients 2025, 17(21), 3387; https://doi.org/10.3390/nu17213387 - 28 Oct 2025
Viewed by 3643
Abstract
Background: Hashimoto’s thyroiditis (HT) is characterised by chronic inflammation of the thyroid gland. The impact of a health-promoting diet and probiotics on health and quality of life, as well as on the anti-thyroid peroxidase antibody (anti-TPO), is increasingly being researched. However, the [...] Read more.
Background: Hashimoto’s thyroiditis (HT) is characterised by chronic inflammation of the thyroid gland. The impact of a health-promoting diet and probiotics on health and quality of life, as well as on the anti-thyroid peroxidase antibody (anti-TPO), is increasingly being researched. However, the relevance of these factors to the course of HT is yet to be fully established. Objective: The aim of this study was to assess the impact of a 12-week nutritional intervention, comprising a rational, health-promoting diet supplemented with the probiotic strain Lactiplantibacillus plantarum 299v (Lp299v), on eating habits, nutritional status, health and quality of life in patients diagnosed with HT. Methods: The 12-week study involved 64 female patients with HT, divided into two groups: the NE+Lp299v group, which received nutritional education and Lp299v (n = 32); and the NE+placebo group, which received nutritional education and placebo (n = 32). Before and after the intervention, anthropometric parameters, body composition analysis, blood pressure, blood anti-TPO levels, dietary habits, quality of life, and gastrointestinal symptoms were assessed. Results: The NE+Lp299v intervention improved overall quality of life (60.94 pts. vs. 35.94 pts.), including 12 of 14 domains, and the diet quality index (11.03 pts. vs. 18.50 pts.). The NE+placebo group improved overall quality of life (54.69 pts. vs. 39.84 pts.), including 3 of 14 domains, and the diet quality index (12.34 pts. vs. 19.18 pts.). Anti-TPO blood levels and body mass index did not improve in either group. Conclusions: Lp299v can enhance the efficacy of nutritional education in improving the quality of life of individuals diagnosed with HT. However, these benefits appear to be independent of anti-TPO levels. Full article
(This article belongs to the Section Nutrition in Women)
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16 pages, 1702 KB  
Review
Autoimmune Thyroid Diseases and Physical Activity and Sports—More Unknowns than Facts
by Monika Skrzypiec-Spring, Andrzej Pokrywka, Adam Szeląg and Agnieszka Zembroń-Łacny
Biomedicines 2025, 13(10), 2352; https://doi.org/10.3390/biomedicines13102352 - 25 Sep 2025
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Abstract
Background: Chronic autoimmune thyroiditis, also known as Hashimoto’s thyroiditis (HT) or chronic lymphocytic thyroiditis whose pathophysiology includes both cellular (T-cell mediated) and humoral (B-cell mediated) immune responses, leads to the destruction of thyroid follicular cells and progressive fibrosis of the thyroid gland. While [...] Read more.
Background: Chronic autoimmune thyroiditis, also known as Hashimoto’s thyroiditis (HT) or chronic lymphocytic thyroiditis whose pathophysiology includes both cellular (T-cell mediated) and humoral (B-cell mediated) immune responses, leads to the destruction of thyroid follicular cells and progressive fibrosis of the thyroid gland. While hypothyroidism is a common autoimmune disease, athletes may experience unique challenges related to its diagnosis and management within the context of training programme, competition and anti-doping regulations. In turn, it is known that moderate physical exercise can have a positive effect on the immune system, while excessive exercise can cause unfavourable changes in this system. Therefore, we aimed (1) to identify the interplay between physical activity and autoimmune thyroid disease, (2) to quantify changes in thyroid function associated with physical activity, and (3) to explain the underlying mechanisms of autoimmune thyroiditis in athletes. Methods: The medical database PubMed/MEDLINE was searched in the time period 2004–2025, where 12 publications met the inclusion criteria and were ultimately included for further evaluation according to the RAMESES (Realist and Meta-narrative Evidence Syntheses: Evolving Standards). Results: The reviewed studies have clearly indicated that physical exercise has a beneficial effect on thyroid function, and two studies reported that non-excessive physical exercise leads to a decrease in TPO-Ab concentrations. Conclusions: The beneficial effect of physical exercise on thyroid function and immune response underlines the need for further well-designed studies to formulate specific guidelines for patients with HT, as well as for athletes with autoimmune thyroid disease. Similarly, there is a need to evaluate the prevalence of thyroid hormone use among amateur and professional athletes in order to establish prevention strategies. Full article
(This article belongs to the Special Issue Thyroid Disorders: Current Status and Future Prospects)
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14 pages, 664 KB  
Article
Non-Thyroidal Illness Syndrome and Thyroid Autoimmunity in Hospitalized COVID-19 Patients: A Retrospective Study
by Ewa Kozłowska, Milena Małecka-Giełdowska and Olga Ciepiela
J. Clin. Med. 2025, 14(19), 6784; https://doi.org/10.3390/jcm14196784 - 25 Sep 2025
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Abstract
Background: Thyroid dysfunction, including non-thyroidal illness syndrome (NTIS), is commonly observed in critically ill patients and has been reported in COVID-19, particularly in those with severe disease. NTIS is defined by low free triiodothyronine (fT3) with normal or low thyroid-stimulating hormone (TSH) [...] Read more.
Background: Thyroid dysfunction, including non-thyroidal illness syndrome (NTIS), is commonly observed in critically ill patients and has been reported in COVID-19, particularly in those with severe disease. NTIS is defined by low free triiodothyronine (fT3) with normal or low thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels. Thyroid autoantibodies may also reflect immune system activation. The relationship between thyroid hormone alterations, autoimmunity, and clinical severity in COVID-19 remains incompletely understood. Methods: We conducted a retrospective study of 276 patients hospitalized with COVID-19, including 138 in the intensive care unit (ICU) and 138 in general wards. A control group of 110 hospitalized, non-infected patients was also analyzed. Serum concentrations of TSH, fT3, fT4 and reverse T3 (rT3) were measured. The presence of anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and thyrotropin receptor antibodies (TRAb) was assessed. Results: NTIS was observed in 44.2% of ICU patients, 18.1% of non-ICU patients, and 1.8% of controls. The fT3/rT3 ratio was lowest in ICU patients (median 0.11 vs. 0.16 in non-ICU and 0.22 in controls). Thyroid autoantibodies were significantly more prevalent in COVID-19 patients than in controls, with anti-TPO antibodies being the most frequently detected. Their presence, even in patients without known thyroid disease, may reflect immune activation associated with SARS-CoV-2 infection. Conclusions: NTIS and thyroid autoimmunity are frequent in hospitalized COVID-19 patients and may reflect disease severity and immune activation. Our study highlights the prognostic relevance of routine thyroid testing, including the fT3/rT3 ratio and combined autoantibody positivity (notably the triple-positive pattern), by directly comparing ICU and non-ICU patients with a non-COVID control group. Full article
(This article belongs to the Special Issue COVID-19 and Endocrine Complications)
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11 pages, 1003 KB  
Article
Reference Intervals and Cut-Off Values for Thyroid Tests in the Croatian Adult Population on the Snibe MAGLUMI X6 Immunoassay Analyzer
by Ivana Lapić, Dragana Šegulja, Željkica Jakoplić, Iva Lukić and Dunja Rogić
Diagnostics 2025, 15(18), 2360; https://doi.org/10.3390/diagnostics15182360 - 17 Sep 2025
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Abstract
Background/Objectives: To establish reference intervals (RIs) and cut-off values for thyroid-related tests on the MAGLUMI X6 immunoassay analyzer (Snibe Diagnostic, Shenzhen, China) in an adult Croatian population. Methods: This study included 305 healthy individuals who underwent regular preventive medical checkup. The following [...] Read more.
Background/Objectives: To establish reference intervals (RIs) and cut-off values for thyroid-related tests on the MAGLUMI X6 immunoassay analyzer (Snibe Diagnostic, Shenzhen, China) in an adult Croatian population. Methods: This study included 305 healthy individuals who underwent regular preventive medical checkup. The following tests were determined in serum: thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), reverse triiodothyronine (revT3), total binding capacity of thyroglobulin (T-uptake), thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO) and thyroid receptor antibodies (TRAb). TSH, TT3, TT4, FT3, FT4, Tg, revT3 and T-uptake results were used for calculating double-sided 95% RIs between the 2.5th and 97.5th percentiles. For anti-Tg, anti-TPO and TRAb, right-sided cut-offs that correspond to the 95th percentile were determined. Results: Reference intervals for TSH, TT4, FT3, FT4, Tg, T-uptake and revT3 did not differ by gender (p > 0.05) and were 0.77–5.04 mIU/L, 69.9–127.7 nmol/L, 3.84–6.20 pmol/L, 13.8–19.7 pmol/L, 1.8–51.2 µg/L, 0.9–1.2 TBI and 0.44–0.73 ng/mL, respectively. The RI for TT3 was different for males (1.49–2.53 nmol/L) and females (1.43–2.81 nmol/L), p = 0.021. A single cut-off for anti-TPO was established (<18 kIU/L). Differences in cut-offs for males and females were obtained for anti-Tg (<72 and <104 kIU/L, respectively) and TRAb (0.6 and 0.9 IU/L, respectively). Conclusions: This is the first study to determine RIs for thyroid function tests in Croatian adults on the Snibe analytical platform. The obtained results point out to the use of population- and immunoassay-specific RIs. For TT3, anti-Tg and TRAb gender-specific RIs should be considered. Full article
(This article belongs to the Special Issue Advances in Laboratory Analysis and Diagnostics)
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