Endokrynologia Polska最新文献

As life expectancy increases worldwide, diseases associated with aging are becoming an increasing challenge in medical care. One of them is senile osteoporosis, which often leads to fragility fractures and numerous subsequent complications, such as disability, chronic pain, and even death. Although osteoporosis is common in the elderly, data on its epidemiology, pathogenesis, and treatment are still lacking. Moreover, it is often diagnosed and treated only after a fracture occurs, which is associated with a significant reduction in quality of life and the generation of high costs. A better understanding of the pathomechanisms of senile osteoporosis is essential for early diagnosis, prevention, and the development of new therapies. This article reviewed current medical knowledge on osteoporosis in the elderly and its epidemiology, etiopathogenesis, diagnosis, and treatment.

Precise assessment of Graves` orbitopathy (GO) predicts therapeutic strategies. Various imaging techniques and different measurement methods are used, but there is a lack of standardization. Traditionally, the Clinical Activity Score (CAS) has been used for assessing GO, especially for evaluating disease activity to predict response to glucocorticoid (GC) therapy, but technological developments have led to a shift towards more objective imaging methods that offer accuracy. Imaging methods for Graves' orbitopathy assessment include ultrasonography (USG), computed tomography (CT), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT). These can be divided into those that assess disease activity (MRI, SPECT) and those that assess disease severity (USG, CT, MRI, SPECT). USG is the accessible first-aid tool that provides non-invasive imaging of orbital structures, with a short time of examination making it highly suitable for initial evaluation and monitoring of GO. It does have limitations, particularly in visualizing the apex of the orbit. Initially, orbital CT was thought to provide more accurate morphological information, particularly in extraocular muscles, and superior visualization of bone structures compared to MRI, making it the imaging modality of choice prior to planned orbital decompression; however, it has difficulty in accurately assessing the inflammatory activity stages of GO. Although CT offers a better view of deeper-lying tissue, it is limited by radiation exposure. MRI is best suited for follow-up examinations because it offers superior soft tissue visualization and precise tissue differentiation. However, it is not specific for orbital changes, the examination is very expensive, and it is rarely available. Recent literature proposes that nuclear medicine imaging techniques may be the best discipline for assessing GO. SPECT fused with low-dose CT scans is now used to increase the diagnostic value of the investigation. It provides functional information on top of the anatomical images. The use of cost-effective radioisotope - technetium-99m (99mTc)-DTPA - gives great diagnostic results with short examination time, low radiation exposure, and satisfactory spatial resolution. Nowadays, 36 years after CAS development and with technological improvement, researchers aim to integrate artificial intelligence tools with SPECT/CT imaging to diagnose and stage GO activity more effectively.

Estrogenic endocrine disruptors (e-EDCs) are synthetic or natural compounds present in the environment with the capacity of modulate molecular pathways regulated by estrogen hormones. Scientific evidence suggests a link between e-EDCs exposure and the development of various types of cancers in organs as prostate, breast, cervix, uterus, colon, lung, liver, and others. Interestingly, synthetic and natural e-EDCs role on cancer development include both preventive and promotive mechanisms, that depend on their concentration and exposure period. The molecular action mechanisms of e-EDCs include diverse signaling pathways such as hormone-dependent gene expression, agonism or antagonism of hormone action, among others. This article reviews the studied molecular signaling pathways that underlie the natural and synthetic e-EDCs effects on the development of various types of cancer.

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Introduction: The objective was to assess the triglyceride-glucose (TyG) index and the homeostatic model assessment for insulin resistance (HOMA-IR) in the evaluation of insulin resistance in patients with acromegaly and to compare results with healthy controls.

Material and methods: A retrospective case-control study was conducted at the Department of Endocrinology, Necmettin Erbakan University, Meram Faculty of Medicine. The study included 50 acromegalic patients and 50 age- and sex-matched healthy controls.

Results: The median age and sex distribution were similar between the acromegaly and control groups (p > 0.05). Compared to the control group, acromegalic patients had significantly higher fasting glucose, HbA1c, total cholesterol, triglyceride, TyG index, and AST levels (p < 0.05 for all), while hemoglobin and platelet counts were significantly lower (p < 0.05). Diabetes mellitus (DM) was present in 24.0% of acromegalic patients. Compared to those without DM, acromegalic patients with DM were significantly older, had greater frequency of cardiovascular disease, and higher glucose, HbA1c, and neutrophil levels (p < 0.05). The TyG index showed a significant correlation with fasting glucose in both groups, but it correlated with insulin and HOMA-IR only in controls.

Conclusion: Acromegalic patients exhibit significant metabolic alterations, including higher TyG index levels and increased DM prevalence, despite having similar HOMA-IR values to healthy controls.

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Background: Congenital hypothyroidism (CH) is the most common neonatal disorder, primarily caused by thyroid dysgenesis (TD). While the genetic cause has been identified in less than 5% of TD cases, there is an urgent need to investigate additional gene mutations that may be responsible. In 2018, TUBB1 was identified as a novel candidate gene associated with TD. Nevertheless, further research is required to confirm the role of TUBB1 in TD pathogenesis and the association between TUBB1 mutations and TD in humans. Based on the previous genetic analysis of TUBB1 in 289 Chinese TD patients, this study aimed to further validate the association between TUBB1 and TD, and to explore the pathogenic mechanisms of TUBB1 c.952C>T at the cellular level.

Material and methods: We performed real-time polymerase chain reaction (RT-PCR), western blot, Cell Counting Kit 8 (CCK8), and wound healing assay to evaluate the effect of TUBB1 c.952C>T on gene expression, cell proliferation, and migration.

Results: The c.952C>T mutant decreased the expression of TUBB1 in both mRNA and protein level, and inhibited the proliferation of thyroid cells significantly. Also, c.952C>T mutant showed restrain effects on the migration, although there was no stistical significance. Notably, pathogenic TUBB1 variants were not detected in patients with dyshormonogenesis (DH).

Conclusions: TUBB1 variants confer genetic susceptibility to TD but not DH. The pathogenic variant in TUBB1 was identified in 1.38% (4/289) of our Chinese TD patient cohort, and burden test analysis revealed an association between TUBB1 variants and TD. Functional experimental results indicated that the c.952C>T mutant dominantly affects gene expression and proliferation of thyroid cells.

Introduction: In recent years, the prevalence of T1DM (type 1 diabetes mellitus) and other autoimmune diseases in the paediatric population has been increasing. The aim of this study was to evaluate vitamin D levels among children with newly diagnosed T1DM, taking into account the most common coexisting autoimmune conditions.

Material and methods: The database included 361 patients diagnosed with T1DM between 2020 and 2021, with a mean age of 9.27 ± 4.1 years, 189 boys. Auxological data and biochemical results of routinely performed tests were retrospectively analysed: blood pH and bicarbonate (HCO3-) on gasometry on admission, glycated haemoglobin (HbA1c), levels of antibodies against glutamic acid decarboxylase (GAD), antibodies against tyrosine phosphatase (IA2), antibodies against zinc transporters (ZnT8), 25-hydroxy vitamin D (25(OH)D), anti-IgA tissue transglutaminase antibodies (TTG-IgA), total IgA, levels of antibodies against thyroperoxidase (TPOAb), and antibodies against thyroglobulin (TgAb).

Results: 35.5% of children (n = 128) with T1D presented 25(OH)D deficiency (< 20 ng/mL), 37% (n = 134) had suboptimal levels (20-30 ng/mL), and 25% (n = 90) had optimal vitamin D levels (30-50 ng/mL). 25(OH)D values were inversely proportional to the severity of diabetic ketoacidosis (p < 0.01) and negatively correlated with HbA1c values (p < 0.05). 25(OH)D levels were also found to be negatively correlated with children's age at diagnosis (p < 0.001). Statistical analysis showed no association between 25(OH)D value and body mass index (BMI) Z-score or type of antibodies typical of T1D. There was also no statistically significant difference in vitamin D levels among patients with additional autoimmune processes (antibodies to thyroperoxidase and/or thyroglobulin and antibodies to tissue transglutaminase).

Conclusions: More than one-third of Polish children with newly diagnosed T1D have 25(OH)D deficiency, especially in patients with diabetic ketoacidosis (DKA) at the diagnosis of diabetes. Determination of vitamin D levels should be a routine procedure in children with newly diagnosed T1DM.

Introduction: The proprotein convertase subtilisin/kexin type 9/lectin-like oxidized low-density lipoprotein receptor-1 (PCSK9/LOX-1) axis plays a crucial role in regulating vascular endothelial cell function, but its specific involvement in type 2 diabetes mellitus (T2DM) remains unclear. This study aims to explore the potential mechanism of the PCSK9/LOX-1 axis in high-glucose (HG)-induced vascular endothelial cell dysfunction.

Material and methods: Peripheral blood samples were collected from T2DM patients to analyse the correlation between PCSK9 and blood lipid levels. Human microvascular endothelial cells (HMEC-1) exposed to high glucose concentration were used as a model of diabetic=angiopathy (DA). Levels of PCSK9, reactive oxygen species (ROS), malonodialdehyde (MDA), interleukins (IL): IL-6, IL-1β, superoxide dismutase (SOD), and tumour necrosis factor alpha (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA) and biochemical methods. Additionally, intracellular total cholesterol (TC) and cholesterol ester (CE) levels were detected using enzyme chemistry. Expression of PCSK9 and LOX-1 was assessed through real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting.

Results: Compared to the normal group, PCSK9 levels were significantly elevated in T2DM patients. Furthermore, PCSK9 levels were found to be positively correlated with body mass index (BMI), waistline, triglyceride (TG), cholesterol, low-density lipoprotein cholesterol (LDL-C), glycated hemoglobin (HbAlc), and intracardiac fat pad levels in T2DM patients. HG exposure led to reduced activity of HMEC-1 cells, along with increased levels of apoptosis, oxidative stress, and inflammation, all of which were counteracted by si-PCSK9. The inhibitory effects of si-PCSK9 on LOX-1 expression, as well as TC and CE contents in HMEC-1 cells induced by HG, were observed. Moreover, intervention with oe-LOX-1 reversed the effects of si-PCSK9 in HG-induced HMEC-1 cells.

Conclusion: Silencing of PCSK9 inhibited HG-induced inflammation, oxidative stress, and lipid metabolic dysfunction in HMEC-1 cells via LOX-1.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy affecting women of reproductive age. Except for the typical symptoms of this syndrome, metabolic disorders are relatively common. Metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosis criteria include hepatic steatosis, excessive fat in the liver, and evidence of steatosis. Women with PCOS are more likely to have this kind of liver disease; thus, the diagnosis is essential. Early treatment is crucial in enhancing liver parameters, affecting the disease's overall course. Liver biopsy is the gold standard of MASLD diagnosis, but non-invasive screening methods are preferred due to possible health complications. Insulin resistance (IR), chronic inflammation, and hyperandrogenemia contribute to MASLD development in PCOS patients. Dysregulation of insulin signaling in the ovaries of PCOS women causes an increase in androgen production. Hyperandrogenism has been taken as the cofactor and independent indicator contributing to the mentioned disease. Excess of androgens in PCOS-affected women may be a guideline for running some MASLD tests to detect ongoing liver steatosis early. Calculators like FIB-4 (fibrosis index based on four factors), BAAT [body mass index (BMI), age, alanine transferase (ALT), triglycerides], and FLI (fatty liver index) are used to detect liver fibrosis or steatosis, making them the right tools for screening among PCOS patients if we aim to prevent further consequences of MASLD. The ultrasound evaluation of MASLD and liver fibrosis is an adequate tool due to its non-invasiveness, low cost, and high availability. Transient elastography makes it possible to find liver steatosis in PCOS patients with high sensitivity. Liver fibrosis interconnects frailly with PCOS; therefore, using FibroScan could be helpful as a screening tool, especially in young patients. If the aim is to rule out significant fibrosis, methods regarding fibrosis (FibroScan, FIB-4, BAAT) are preferable. Unfortunately, these methods are unsuitable for distinguishing between absent and initial fibrosis, and their usefulness is limited regarding fibrosis prevention. Methods regarding steatosis (emphasizing TE, FLI as a second-choice method) can detect liver steatosis, making them the right tool for screening among adult and teenage PCOS patients if the aim is to prevent further consequences of MASLD.