Search Results (11,872)

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

Acromegaly is caused by an excessive secretion of growth hormone and the secondary elevation of IGF-1 levels, leading to progressive changes in multiple body systems, including the craniofacial region and oral cavity. Dental manifestations such as mandibular overgrowth, macroglossia, malocclusion, periodontal disease, and prosthetic difficulties represent not only a clinical component of the disease but also a significant therapeutic and diagnostic challenge. The aim of this review is to present the current state of knowledge on the relationship between acromegaly and oral health and to analyze the role of interdisciplinary collaboration between endocrinologists and dentists in patient care. For this narrative review, a literature search was conducted in the PubMed, Scopus, and Web of Science databases covering the period from 2000 to 2025. Sixty-two peer-reviewed publications meeting the methodological and thematic criteria were included in the analysis, including original studies, meta-analyses, systematic reviews, and case reports. The results indicate significant correlations between disease activity and the severity of periodontal and microbiological changes, while effective endocrine treatment only results in the partial regression of morphological changes. Particular attention was given to the role of the dentist in recognizing the early symptoms of the disease, planning prosthetic and surgical treatment, and monitoring therapy-related complications. Interdisciplinary collaboration models, including integrated clinics and co-managed care, were also described as optimal systemic solutions for improving treatment quality. The conclusion drawn from the analysis are as follows: there is a need for the permanent integration of dentistry into the standard of interdisciplinary care for patients with acromegaly, in both diagnostic and therapeutic dimensions. Increasing awareness among dentists and developing integrated collaboration models may reduce the time to diagnosis, improve patients’ quality of life, and enable the more effective management of craniofacial complications in the course of this rare disease. Full article

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment. Full article

Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed to assess the preoperative diagnostic value of circulating miR-146a and miR-221 in patients undergoing thyroidectomy. A total of 56 patients were included, of whom 24 had malignant and 32 had benign thyroid lesions confirmed by histopathology. Preoperative plasma levels of miR-146a and miR-221 were quantified using qRT-PCR, and relative expression was calculated with the 2^−ΔΔCt method. miR-221 expression was significantly higher in malignant cases, with an area under the ROC curve of 1.00, achieving 100% sensitivity and specificity at the optimal threshold. miR-146a showed no significant discriminatory ability. Weak correlations were observed between miRNA expression and clinical parameters such as age, TIRADS score, or thyroid volume. Logistic regression including miR-221 led to perfect separation, indicating strong predictive capacity but precluding multivariate modeling. These findings suggest that circulating miR-221 may serve as a highly accurate biomarker for thyroid malignancy and warrant further validation in larger, prospective cohorts. Full article

Background/Objectives: Mitotane is a key component in the treatment of adrenocortical carcinoma (ACC), but its endocrine side effects in children remain under-characterized. Methods: We conducted a retrospective analysis of 11 pediatric patients (6 males, 5 females) diagnosed with ACC and followed between 2000 and 2025. Seven received mitotane therapy. Data included age at diagnosis, treatment duration and dosage, serum mitotane levels, and endocrine complications. Results: The mean age at diagnosis was 6.6 ± 1.45 years, with a mean follow-up of 10.05 ± 2.45 years. Patients received mitotane for an average of 2.5 ± 0.54 years, with a mean daily dose of 2805.5 ± 145.82 mg and a mean serum level of 16.1 ± 5.92 mg/mL. All mitotane-treated patients developed adrenal insufficiency, requiring supraphysiological hydrocortisone replacement. Four also required mineralocorticoid therapy. Five developed precocious puberty; two males presented with prepubertal gynecomastia; three females were managed with GnRH analogs or aromatase inhibitors followed by estrogen receptor antagonists. Four patients developed central hypothyroidism, treated with levothyroxine. A positive correlation was found between mean serum mitotane levels and the onset of precocious puberty (p = 0.04), while mitotane levels correlated negatively with the development of central hypothyroidism (p = 0.001). Conclusions: Mitotane therapy in pediatric ACC is strongly associated with significant endocrine dysfunction. These findings emphasize the need for proactive, multidisciplinary endocrine management throughout treatment. Full article

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article

Purpose: The present study aims to evaluate alterations in the peripapillary retinal nerve fiber layer (RNFL) thickness in pediatric patients following surgical resection of childhood-onset craniopharyngioma (CP) and to identify tumor characteristics and other factors influencing these alterations, including changes in the lesion’s location. Design: retrospective clinical cohort study. Methods: A retrospective analysis was conducted on 73 eyes from 38 patients with CP and 64 eyes from 32 age- and sex-matched healthy controls. The mean age of the CP patients was 10.3 ± 4.2 years (range 4–17), while the control group had a mean age of 10.5 ± 3.1 years (range 4–17). Optical coherence tomography (OCT) was used to assess the peripapillary RNFL thickness in the study and control groups. RNFL thickness was analyzed in the superior, inferior, and average sectors, as well as across eight optic nerve sectors. Tumor characteristics were evaluated to determine their correlation with changes in RNFL thickness in individual sectors. Results: Postoperative thickness of peripapillary RNFL in all individual sectors was significantly reduced in the CP group compared to healthy controls. Location, tumor volume, maximum tumor diameter, calcification, ventriculoperitoneal shunt, surgery technique, total resection, presence of Rosenthal fibers, and reoperation due to progression or recurrence correlated with damage to RNFL. Conclusions: CP is associated with significant reductions in RNFL thickness, indicating the tumor’s impact on optic nerve fibers. OCT is a valuable tool for monitoring visual pathway impairment and postoperative outcomes. Correlations between RNFL thickness in individual sectors and clinical parameters may offer valuable insights for diagnosis and monitoring, underlining their potential role in predicting visual outcomes. Regular RNFL evaluation should be integrated into the long-term care of CP patients to optimize visual prognosis and detect progressive or residual damage. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant comorbidity in individuals with type 1 diabetes (T1D), despite its historical association with type 2 diabetes. This review focuses on summarizing current findings regarding the role of insulin resistance in the development of MASLD in T1D, as well as examining the relationship between MASLD and diabetes-related complications. We will also briefly discuss the prevalence, diagnostic challenges, associated complications, and potential mechanisms underlying MASLD in T1D. Although insulin resistance is well established in MASLD among those with type 2 diabetes, its role in T1D requires further clarification. Emerging markers, such as the estimated glucose disposal rate, offer early insight into this relationship. MASLD in T1D is linked to both microvascular and macrovascular complications, including nephropathy, retinopathy, neuropathy, and cardiovascular disease. Variability in prevalence estimates reflects inconsistencies among imaging modalities, emphasizing the need for standardized, non-invasive diagnostic approaches. Recognizing and addressing MASLD and its links to insulin resistance and diabetes complications in T1D is vital for mitigating long-term complications and enhancing clinical outcomes. Full article

Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η²_p = 0.188–0.197), LH (η²_p = 0.061–0.068), and FSH (η²_p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach. Full article

Objective: Cervical pregnancy (CP) accounts for less than 1% of all ectopic pregnancies. The standard of management for CP is still under detailed investigation; however, among the known treatment methods, super-selective uterine artery embolization (UAE) and the use of methotrexate (MTX) have emerged as effective and minimally invasive options in recent years. Our aim is to present our center’s experience and provide available evidence evaluating the efficacy of UAE in the treatment of CP. Materials and Methods: This single-center and retrospective study evaluated the procedural and clinical outcomes of patients with CP who underwent endovascular uterine embolization with MTX between 2017 and 2024. Both procedural and clinical efficacy and safety, as well as the rate of complications and long-term outcomes, were noted. Results: A total of nine patients were diagnosed with CP (imaging examination included transvaginal ultrasound and/or magnetic resonance imaging) and referred for endovascular treatment. The mean age of the patients was 36.7 years, and the mean gestational age on admission was 9 weeks. In all cases, selective catheterization of supplying vessels and subsequent embolization with a mixture of methotrexate and gel sponge was carried out. The technical success rate was 100% with no complications. Follow-up ultrasound confirmed the disappearance of the flow signal around the intracervical gestational sac in all cases. Conclusions: In conclusion, this retrospective study demonstrated the procedural and clinical safety and efficacy of uterine artery embolization in patients with cervical pregnancy. This is why endovascular therapy should be proposed to these individuals and be included in treatment options discussed during multidisciplinary boards. Full article

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article

Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article

Background/Objectives: The association between chronic kidney disease (CKD) and body size phenotypes in metabolically diverse but apparently healthy adult populations remains inadequately understood. This study investigated the association between CKD and body size phenotypes in a nationally representative sample of healthy Korean adults. Methods: Data from 8227 participants in the 2019–2021 Korean National Health and Nutrition Examination Survey were analyzed. Participants were categorized into four body size phenotypes by combining BMI status (normal weight or obese) with metabolic health status (healthy or abnormal)—MHNW (Metabolically Healthy Normal Weight), MANW (Metabolically Abnormal Normal Weight), MHO (Metabolically Healthy Obese), or MAO (Metabolically Abnormal Obese). CKD was defined based on the urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR). To assess the association between CKD and body size phenotypes, multivariable logistic regression analyses were performed. Results: CKD prevalence was 4.4%. MANW and MAO made up 12.6% and 26.4% of the CKD group, compared to 5.0% and 13.2% of the non-CKD group. CKD prevalence by phenotype was observed as follows: MHNW, 3.2%; MANW, 10.5%; MHO, 4.0%; and MAO, 8.5%. CKD odds were highest in the MAO group (OR: 3.770, 95% CI: 2.648–5.367), followed by the MANW (OR: 2.492, 95% CI: 1.547–4.016) and MHO (OR: 1.974, 95% CI: 1.358–2.870) groups. MAO individuals carried a higher CKD risk than MHO individuals (OR: 1.897, 95% CI: 1.221–2.945). Conclusions: Among apparently healthy adults, body size phenotypes—particularly those with metabolic abnormalities—were significantly associated with the presence of CKD. These findings highlight the need to assess both metabolic health and body composition for effective CKD prevention and management. Full article

Background and Clinical Significance: Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant disorder caused by mutations in the MEN1 gene. Although primarily characterized by endocrine tumors, renal manifestations remain underreported. Case Presentation: We report a three-generation family carrying a pathogenic MEN1 mutation (c.1351-3_1359del) with a co-occurring Claudin 16 (CLDN16) variant (c.324+13C>G). Genetic testing included MLPA and whole-exome sequencing (WES), with bioinformatics analysis validating variant pathogenicity. All three patients exhibited primary hyperparathyroidism, hypercalcemia, hypercalciuria, early nephrocalcinosis, and renal hypomagnesemia. The CLDN16 variant, previously considered benign, co-segregated with hypomagnesemia and renal involvement, suggesting a potential modifying role. Conclusions: These findings support the need for comprehensive genetic screening in MEN1 patients with atypical renal presentations. Concomitant genetic variations can alter the principal phenotype. Full article