Search Results (335)

People with Down syndrome represent a highly vulnerable population, frequently showing vitamin D deficiency together with an elevated risk of metabolic and neuromuscular dysfunction. This susceptibility derives from several factors, including muscular hypotonia, excess body weight, thyroid abnormalities, and immune dysregulation. The coexistence of these conditions compromises bone and muscle health, increases cardiometabolic risk, and reduces motor abilities and coordination, thereby predisposing individuals to falls, sarcopenia, sarcopenic obesity, and long-term disability. Vitamin D, traditionally known for its essential role in bone health, is now recognized as a pleiotropic hormone regulating immune responses, metabolic balance, and muscle performance. Its deficiency is increasingly linked to obesity, insulin resistance, diabetes mellitus, dyslipidemia, and metabolic syndrome. These adverse outcomes are mediated through mechanisms involving chronic inflammation, oxidative stress, mitochondrial impairment, and disrupted adipokine signaling. This review integrates current molecular, cellular, and clinical evidence on the multifaceted actions of vitamin D in Down syndrome. Particular emphasis is placed on its effects on insulin signaling, adipose tissue metabolism, inflammatory regulation, and muscle strength. Finally, vitamin D is discussed as a biomarker and therapeutic target to guide personalized interventions aimed at improving metabolic health, maintaining muscle function, and promoting long-term independence in this high-risk population. Full article

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

Background: Graves–Basedow disease (GBD) is an autoimmune thyroid disorder characterized by loss of tolerance to the thyrotropin receptor, with clinical manifestations such as a hyperadrenergic state, goiter, orbitopathy, and myxedema, inter alia. Selenium is a micronutrient, essential for the synthesis of selenoproteins. Selenium deficiency has been linked to an increased risk and exacerbation of GBD and GBD orbitopathy; therefore, it has been suggested that supplementation with this micronutrient could modify some outcomes associated with both conditions. Objectives: The objective of this scoping review was to synthesize and analyze the clinical trials that have evaluated the effectiveness of selenium on different outcomes in patients with GBD or GBD orbitopathy. Methods: The following databases were consulted: PubMed/Medline, Scopus, Biosis, ProQuest, Web of Science, and Google Scholar; and the search terms ‘Graves-Basedow disease’ or ‘Graves’ disease’ or ‘hyperthyroidism’ or ‘Graves’ hyperthyroidism’ or ‘selenium or selenium supplementation’ and ‘effectiveness’ were used. The search was limited to articles published in English between January 2000 and March 2025. To reduce selection bias, each article was reviewed independently by three authors using the Rayyan web tool and the JBI Critical Appraisal Checklist. Results: A total of 15 studies were identified (11 on patients with GBD and 4 on patients with GBD orbitopathy). In GBD, selenium supplementation was associated with significant improvements in TSH, FT4, FT3, TPOAb, TgAb, and TRAb levels; while in GBD orbitopathy, a positive effect of selenium supplementation was found on multiple clinical outcomes. Conclusions: Selenium supplementation in patients with GBD or GBD orbitopathy is associated with favorable biochemical and clinical outcomes. Full article

Iodine is an essential micronutrient that is required for thyroid hormone (TH) synthesis. However, adequate maternal thyroid function is critical for fetal growth and neurodevelopment. Pregnancy increases iodine requirements due to enhanced renal clearance, higher maternal TH production, and transplacental transfer, making pregnant women especially vulnerable to iodine deficiency. In this review, we examine the molecular mechanisms of TH synthesis and regulation, placental transport and metabolism, and the physiological adaptations of thyroid function during gestation. We also analyze the clinical and public health consequences of iodine imbalances, ranging from deficiency to excess. Evidence indicates that mild iodine deficiency—which is common even in developed countries—can lead to maternal thyroid overstimulation, increased thyroglobulin levels, altered T3/T4 ratios, and enlarged thyroid volume, while severe deficiency results in maternal and fetal hypothyroidism with irreversible neurocognitive impairment in the offspring. Conversely, excessive iodine intake may impair fetal thyroid function through mechanisms such as the Wolff–Chaikoff effect. In conclusion, ensuring balanced iodine intake through iodized salt, supplementation, and routine thyroid monitoring during pregnancy is essential to protect maternal health and optimize early neurodevelopment. Full article

Frozen shoulder (FS), traditionally regarded as an idiopathic musculoskeletal disorder characterized by pain, stiffness, and capsular fibrosis, is increasingly recognized as the clinical manifestation of systemic endocrine, metabolic, vascular, and immunological dysfunctions. This narrative review reframes FS within a broader neuro–endocrine–immunometabolic model, emphasizing the central role of estrogen deficiency, resistance, and receptor-level disruption, together with their interactions with thyroid dysfunction, endothelial health, and lifestyle-related low-grade inflammation (LGI). Evidence from epidemiological, clinical, and mechanistic studies shows that estrogen signaling failure weakens anti-inflammatory, antifibrotic, and antioxidant defenses, predisposing peri- and postmenopausal women to more severe FS phenotypes. Thyroid dysfunction, particularly hypothyroidism, further contributes to fibrosis and pain sensitization. Endothelial dysfunction—driven by poor diet, advanced glycation end-products (AGEs), and oxidative stress—impairs vascular integrity and promotes local microvascular inflammation. In parallel, lifestyle factors such as sedentarism, circadian misalignment, psychosocial stress, and environmental exposures sustain systemic LGI and hormonal resistance. Together, these interconnected mechanisms suggest that FS is not merely a localized joint pathology but a systemic disorder requiring integrative clinical strategies that combine orthopedic management with endocrine evaluation, metabolic monitoring, dietary interventions, circadian health, and stress regulation. In addition, this review outlines specific clinical implications, highlighting how an integrative, personalized approach that targets hormonal, metabolic, vascular, and lifestyle dimensions may improve pain, function, and long-term prognosis in FS. This paradigm shift underscores the need for future research to focus on stratified patient profiling and interventional trials targeting hormonal, vascular, and lifestyle axes to improve outcomes, particularly in women who remain disproportionately affected by FS. Full article

Background: Obesity has been proposed as a risk factor for differentiated thyroid carcinoma (DTC), though findings in the literature remain conflicting. While some studies suggest an association between elevated body mass index (BMI) and thyroid malignancy, others attribute this link to diagnostic bias. The Calabria region in Southern Italy, historically affected by iodine deficiency and endemic goiter, offers a valuable population for investigating this relationship. Objective: This study aimed to evaluate the association between obesity and clinical, sonographic, and cytological characteristics of thyroid nodules in a Calabrian cohort undergoing fine-needle aspiration biopsy (FNAB). Methods: This retrospective observational study included 1192 patients evaluated at a single endocrine referral center between 2015 and 2024. Patients were stratified by BMI (<30 vs. ≥30 kg/m²). Demographic, biochemical, ultrasound, and cytological data were collected and analyzed. Cytological results were classified according to the SIAPEC 2014 system. Results: Obese patients had significantly larger thyroid nodules in terms of anteroposterior and transverse diameters, as well as overall volume (p < 0.05). However, the distribution of high-risk cytological categories (TIR 3B, TIR 4, and TIR 5) did not differ significantly between obese and non-obese patients (9.4% in both groups). Multivariate analysis confirmed that BMI was not an independent predictor of malignancy risk (OR 0.988; p = 0.723), whereas younger age was inversely associated with malignancy. Conclusions: Obesity appears to influence thyroid nodule size but does not constitute an independent risk factor for cytological malignancy. BMI should not influence indications for FNAB or subsequent treatment decisions. Thyroid nodule management should instead rely on ultrasound risk stratification and cytological findings. Special attention should be given to younger patients as they may carry a higher malignancy risk. Full article

Background/Objectives: Thyroid hormone deficiency may impair bone metabolism, but its mandibular impact remains uncertain. We aimed to compare the prevalence of altered Mandibular Cortical Index (MCI; C2–C3) and Panoramic Mandibular Index (PMI) on digital panoramic radiographs in adult women with primary hypothyroidism versus euthyroid controls, considering age and key clinical covariates. To our knowledge, this is the first study out of Spain addressing this question. Methods: This is a cross-sectional study (September 2021–June 2024) of 179 white women recruited at a university clinic. Cases were on L-thyroxine for ≥6 months, with TSH > 4.5 mIU/L and normal FT4; controls were euthyroid and untreated. Demographics, reproductive history, and BMI were recorded. Panoramic radiographs (Ratograph EVO 3D; 72 kV, 6 mA, 14.4 s) were analysed; MCI was graded (Klemetti C1–C3) distal to the mental foramen; PMI and mandibular cortical width (MCW) were measured bilaterally. Results: Women with hypothyroidism showed higher BMI and a greater number of years since menopause; age was slightly higher, but the difference was not significant. MCI distribution did not differ between groups (C3 and C2–C3, both p > 0.45). PMI (left/right) was similar (p = 0.253/0.160). Left MCW was higher in hypothyroidism in a crude analysis (4.86 ± 0.98 vs. 4.46 ± 0.94 mm; p = 0.039), but lost significance after age adjustment (adjusted p = 0.191); right MCW showed no differences. Total tooth loss tended to be higher (p = 0.055) without conclusive evidence. Conclusions: In this cohort, primary hypothyroidism was not associated with a differential mandibular cortical pattern by MCI or PMI; the crude MCW difference was explained by age. These Spain-based data refine heterogeneous prior findings and indicate that, in women treated for hypothyroidism, mandibular cortical metrics largely resemble those of their euthyroid peers. Longitudinal and multicentre studies are warranted to clarify trajectories and enhance generalisability. Full article

Background: Differentiated thyroid cancer (DTC) is commonly treated with radioactive iodine (RAI), but resistance to RAI remains a significant clinical challenge. The molecular mechanisms driving dedifferentiation and RAI refractoriness, particularly in BRAF^V600E-mutated tumors, are not fully understood. Methods: RNA sequencing was conducted on BRAF^V600E-mutated DTC and RAIR-DTC tissue samples to identify differentially expressed genes. Gadd45B was identified as significantly downregulated in RAIR-DTC. Functional studies including overexpression and knockdown experiments were performed in thyroid cancer cell lines and xenograft models. Downstream targets, including MAP3K4 and MYCBP, were evaluated through co-immunoprecipitation, luciferase assays, and Western blot. The therapeutic efficacy of recombinant Gadd45B protein in combination with BRAF^V600E and TERT inhibitors was assessed in patient-derived xenograft (PDX) models. Results: Gadd45B overexpression suppressed MAPK pathway activity by interacting with MAP3K4 and downregulated c-MYC stability through competition with MYCBP. These interactions enhanced the expression of iodine-metabolism genes (NIS, TPO, Tg), increased RAI uptake, and reversed tumor dedifferentiation. In vivo, Gadd45B restoration reduced tumor burden and improved RAI uptake. Combined treatment with Gadd45B protein, PLX4720, and BIBR1532 produced synergistic therapeutic effects in PDX models. Conclusions: Gadd45B plays a pivotal role in regulating the differentiation status and RAI sensitivity of BRAF^V600E-mutated thyroid cancer. These findings identify Gadd45B as a promising therapeutic target for restoring RAI responsiveness in RAIR-DTC patients. Full article

Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin D deficiency and oxidative stress (OS) have emerged as key contributors. We aimed to explore the shared immunopathogenic pathways linking these conditions, with a focus on the interplay between vitamin D status and redox imbalance. Methods: An extensive narrative review of the current literature regarding the associations among CSU, vitiligo, and HT, focusing on the role of vitamin D status, OS, and nitrosative stress, and shared immunological pathways was conducted. Discussion: Vitamin D deficiency was consistently observed across all three conditions and is associated with increased disease activity and poorer clinical outcomes. Several polymorphisms in the vitamin D receptor (VDR) and binding protein genes correlate with disease susceptibility. OS and nitrosative stress markers, such as malondialdehyde (MDA) and nitric oxide (NO) metabolites, are elevated in patients with CSU, vitiligo, and HT, and are linked to tissue-specific immune activation, apoptosis, and loss of self-tolerance. Evidence suggests that vitamin D and antioxidant supplementation may provide clinical benefit. In vitiligo, narrowband ultraviolet B (NB-UVB) phototherapy not only promotes repigmentation through melanocyte stimulation but also reduces ROS production and modulates local immune responses. Conclusions: The coexistence of CSU, vitiligo, and HT reflects a broader systemic autoimmune tendency, with vitamin D deficiency and redox imbalance serving as potential unifying mechanisms. Routine assessment of vitamin D levels and OS parameters may enhance diagnostic precision and inform therapeutic strategies. Antioxidant-based interventions represent promising avenues in the integrated management of autoimmune skin and endocrine disorders. Full article

Autoimmune diseases are characterized by immune response dysregulation against self-components, leading to chronic inflammation and tissue damage. Vitamin C (VitC), a water-soluble vitamin with established functions in antioxidant defence and collagen synthesis, has also been of interest based on its potential immunomodulatory effects. This review discusses the role of VitC in the course and progression of (A) autoimmune diseases (multiple sclerosis, rheumatoid arthritis, Sjögren’s disease, type 1 diabetes, Hashimoto’s thyroiditis, pernicious anaemia, antiphospholipid syndrome), (B) other immune-mediated diseases (Crohn’s disease, periodontitis), and (C) Alzheimer’s disease, a neurodegenerative disorder with autoimmune features. Results from clinical, observational, and experimental trials show that VitC deficiency is common in many of these diseases and may contribute to increased oxidative stress and immune disequilibrium. Supplementation has been associated with improved antioxidant levels, control of inflammatory mediators, and, in some cases, clinical outcomes like disease activity decrease or symptom load. Although findings vary across conditions and few large, randomized trials are available, the overall evidence indicates that maintaining good VitC status can be useful in maintaining immune homeostasis and reducing inflammation. VitC should be viewed as an adjunct to be employed safely, perhaps and ideally within larger treatment regimens, but not in place of effective therapies. Further research, including large-scale clinical trials, will be required to determine more clearly optimal dosing, timing of treatment, and patient population most likely to benefit. By integration of current knowledge, this review recognizes both promise in VitC for treatment of autoimmune/immune-mediated disease and promise in its potential use within future treatment regimens. Full article

Background/Objectives: Neonatal screening programmes for thyroid function testing, based on thyroid-stimulating hormone (TSH) assessment, detect both Permanent Congenital Hypothyroidism (PCH) and Transient Congenital Hypothyroidism (TCH). Maternal iodine-deficient dietary intake may result in compensatory neonatal TSH elevation; screening for Congenital Hypothyroidism (CH) is used as an indicator of the degree of iodine deficiency and of its control. In Greece, newborn screening for CH, using TSH measurement in dried blood spots (Guthrie card), began in 1979 through the Institute of Child Health (ICH). Although the general Greek population is considered iodine-replete, most pregnant Greek people are mildly iodine deficient according to the stricter WHO criteria. The aim of this retrospective study was to record the cases of TCH and the main causative factors over a 10-year period (2010–2019) in Greece, when the country was deemed to be iodine-replete. Methods: The number of births in Greece between 2010 and 2019 was retrieved from the Hellenic Statistical Authority (ELSTAT) archives: 952,109 births were recorded. The total number of newborns assessed through the ICH was 951,342 (99%). During this period, 22,391 newborns were identified to have TSH > 7 mIU/L after the second check on the initial card. Among those, 17,992 underwent retesting with a serum sample. Out of the retested newborns, 1979 were screened positive for CH and immediately began treatment with levothyroxine. We followed up with families, paediatricians, and paediatric endocrinologists to determine whether L-thyroxine therapy had been successfully discontinued for at least two months after the child’s third birthday. Successful contact was achieved with 889 individuals. From this group, 329 children had successfully discontinued thyroxine, classified as TCH. Demographic data, including gender, gestational age, and birth weight, were collected from the archives of the ICH. Maternal data, including thyroid medication use and the presence of elevated thyroid autoantibodies during pregnancy and childbirth, were also recorded. Results: Logistic regression analysis revealed that, while controlling for all other predictor variables, the odds ratio of transient hypothyroidism was 2.078 (95% CI: 1.530 to 2.821) for prematurely born children compared to those born at term. The effects of other factors on TCH versus PCH were not significant. Conclusions: It seems that prematurity is the main factor contributing to Transient Congenital Hypothyroidism in Greece, a recently iodine-replete country. Full article

Iodine is an essential element for the synthesis of thyroid hormones. Iodine deficiency leads to a range of health consequences known as iodine deficiency disorders. To assess the iodine nutritional status of a population, urinary iodine (UI) is typically measured. This work introduces a novel and simple analytical method for determining UI using silver triangular nanoplates (AgTNPs) after interfering substances are removed via solid-phase extraction (SPE). The AgTNPs were synthesized and characterized using Transmission Electron Microscopy, UV–vis spectroscopy, and zeta potential measurements. The limit of detection of iodide of the AgTNPs assessed spectrophotometrically was 35.78 µg I⁻/L. However, urine samples interfered with the colorimetric reaction. Thus, an SPE methodology was developed and optimized to eliminate urine interferents that hinder AgTNP performance. A logistic regression analysis was conducted to validate the combined application of SPE and AgTNPs for the qualitative determination of UI. This work demonstrated that the developed SPE methodology eliminates these interferents and extracts iodide from the sample, allowing the accurate determination of UI using AgTNPs. This reliable sample preparation method was then used on actual human urine samples to accurately identify UI deficiency levels. The proposed methodology offers an effective and environmentally friendly approach for monitoring iodine status, without requiring highly complex equipment. Full article

Objective: Obesity induces hypothyroidism with unknown mechanisms. This study investigates the role of (Receptor for Hyaluronan-Mediated Motility (RHAMM) in obesity-associated thyroid dysfunction, focusing on hepatic oxidative stress. Methods: Global RHAMM-deficient mice and their wildtype littermate controls were fed a normal chow diet or high-fat diet (HFD) for 16 weeks. Thyroid function was evaluated by measuring plasma thyroid-stimulating hormone (TSH) levels. The hepatic oxidative response was assessed by measuring signaling pathways associated with nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Results: HFD feeding increased plasma TSH levels in male mice but not in female mice. RHAMM deletion in male mice mitigated HFD-induced TSH elevation, which was associated with enhanced hepatic antioxidant defenses and reduced inflammation. This was evidenced by elevated expression of the Nrf2 target gene NAD(P)H: quinone oxidoreductase 1 (Nqo1), reduced protein carbonylation and nitration levels, and reduced expression of the pro-inflammatory cytokines IL-1β and TNF-α in livers of male RHAMM-deficient mice. Mechanistically, RHAMM deletion decreased AKT/ERK signaling, increased GSK3 signaling, increased CD44 protein expression, and increased Nqo1 levels in the liver. Conclusions: RHAMM promotes obesity-induced thyroid dysfunction by regulating oxidative stress and inflammation in male mice. Targeting RHAMM may provide a novel therapeutic strategy for mitigating obesity-related endocrine and metabolic disorders. Full article

Background/Objectives: Iodine is an important nutrient for the human body, used in the production of thyroid hormones. During pregnancy, a deficiency can cause miscarriage and hypothyroidism, while an excess can cause thyroid dysfunction. Therefore, the objective of this study was to evaluate the factors associated with the iodine nutritional status of pregnant Brazilian women. Methods: This was a cross-sectional, multicenter study conducted with pregnant women over 18 years of age, users of the Unified Health System (SUS). A semi-structured questionnaire was used to obtain sociodemographic information. Iodine status was assessed by urinary iodine concentration (UIC). The iodine content of salt and homemade and industrial seasonings was determined by the titrimetric method. Dietary intake was estimated through a 24-hour dietary recall. The chi-square test and hierarchical multinomial logistic regression were used for statistical analysis. The significance level was set at p ≤ 0.05. Results: Among Brazilian pregnant women, the median UIC was 186.7 µg/L (P25: 118.05 µg/L-P75: 280.93 µg/L). Regarding iodine nutritional status, the prevalence of deficiency was 36.7% (n = 694), above the requirement was 28.7% (n = 543), and excess iodine intake was 3.6% (n = 68). We observed that non-white pregnant women were more likely (OR = 1.83; 95% CI: 1.27–2.64) to have iodine deficiency, and those who did not work were less likely (OR = 0.71; 95% CI: 0.52–0.98). Pregnant women in the last trimester of pregnancy were less likely to have iodine intake above the requirements (OR = 0.52; 95% CI: 0.31–0.88). Conclusions: A substantial proportion of pregnant women had iodine deficiency or intake above the required level. Iodine deficiency is more chance among non-white pregnant women and less chance among those not employed during pregnancy. On the other hand, pregnant women who were in their third trimester of pregnancy were less likely to have iodine intake above the required level. Full article

Thyroid hormone (TH) regulates cell proliferation, differentiation, and metabolism. Increased TH levels in circulation are associated with a higher incidence of age-related macular degeneration. In mice, TH treatment causes photoreceptor degeneration, which is accompanied by an increase in receptor-interacting serine/threonine-protein kinase 3 (RIPK3) in the retina. Here, we investigated the contribution of RIPK3/necroptosis to TH-induced photoreceptor degeneration using mice deficient in RIPK3 and the necroptotic mixed lineage kinase domain-like protein (MLKL). Wild-type (C57BL/6) and mutant mice at postnatal day 30 received triiodothyronine (T3, 20 µg/mL in drinking water) for four weeks, followed by the evaluation of photoreceptor survival/death and retinal function. Deletion of Ripk3 preserved photoreceptor integrity against T3-induced degeneration, evidenced by improved retinal morphology, increased cone density, improved retinal light responses, and reduced cell death. This protection was observed in both global and photoreceptor-specific Ripk3 knockout mice. In contrast, the deletion of Mlkl did not protect photoreceptors. This work supports the view that RIPK3, but not MLKL, contributes to TH-induced photoreceptor degeneration. The lack of protection from Mlkl deletion suggests that RIPK3’s action is likely mediated via a necrosome-independent mechanism. These findings provide significant insight into how TH signaling induces photoreceptor degeneration and implicate RIPK3 as a potential therapeutic target. Full article