Hormone and Metabolic Research最新文献

Klinefelter syndrome (KS) is the most common genetic cause of male infertility, affecting approximately 1 in 660 men. It is characterized by the presence of one or more extra X chromosomes. Literature suggests an increased risk of venous thromboembolic events (VTE) in KS. Testosterone replacement therapies (TRT) are commonly used in KS to improving well-being, body composition and sexual function. However, TRT may influence the risk of VTE. Our objective was to assess the rate of VTE, and its association with TRT, in a cohort of KS patients. Data on VTE, TRT usage, and demographics were obtained from a hospital-based KS clinic database. 179 patients were included. The median age was 35 years (interquartile range [IQR] 29-42 years). 118 (66%) had received TRT prior to the review in clinic. 11 patients (6.1%) had at least one VTE. The median age of first VTE was 35 years (range 19-73 years). The incidence of a VTE was 17.0 (95% confidence interval [CI] 8.5-30.3) events per 10,000 person-years. Five of the 11 patients had received TRT prior to VTE. There was no significant association between receiving TRT and suffering a VTE (p=0.1). The incidence rate of VTE in KS patients observed here is approximately four-fold higher than in the general adult male population. This is consistent with previous studies that have showed an increase rate ratio of between 2.1 and 12.1, dependent on age. This study did not show a statistically significant difference in VTE incidence based on the use of TRT.

Postoperative hypocalcemia caused by hypoparathyroidism and vocal cord paralysis remain common complications following thyroid surgery. Sex and metabolic comorbidities may influence their occurrence. We conducted a multicenter cross-sectional analysis using anonymized data from 3,365 patients (1,517 hemithyroidectomies and 1,848 thyroidectomies) treated at 27 German hospitals between 2019 and 2024. Primary outcomes were postprocedural hypoparathyroidism and vocal cord paralysis, identified via ICD-10 codes. Associations with age, sex, obesity, diabetes, thyroid pathology, and surgical extent were analyzed using multivariable logistic regression. Postoperative hypoparathyroidism was more frequent after thyroidectomy (3.6%) than hemithyroidectomy (0.3%). Female sex was positively associated with postoperative hypoparathyroidism (odds ratio: 2.30; 95% confidence interval: 1.11-4.77), while obesity was inversely associated with postoperative hypoparathyroidism (odds ratio: 0.15; 95% confidence interval: 0.04-0.63). Vocal cord paralysis was observed in 1.7% of hemithyroidectomy and 1.0% of thyroidectomy cases. Factors significantly or tendentially associated with vocal cord paralysis included malignant neoplasm (odds ratio: 4.00; 95% confidence interval: 1.37-11.64), diffuse goiter (odds ratio: 4.94; 95 % confidence interval: 0.86-28.37), parathyroidectomy (odds ratio: 3.47; 95% confidence: 1.04-11.59), and diabetes mellitus (odds ratio: 3.09; 95% confidence: 0.98-9.74). Individual risk profiling and intraoperative neuromonitoring are critical to improving outcomes after thyroid surgery.

Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) are rare causes of hyperthyroidism that frequently present diagnostic and therapeutic challenges. This study characterizes the clinical, biochemical, radiological, and histopathological features of TSHomas, evaluates long-term outcomes, and identifies factors influencing remission and recurrence. We retrospectively analysed 12 patients with TSHoma treated between January 2003 and February 2025 at a tertiary endocrine referral centre. Clinical presentation, hormonal profiles, imaging characteristics, histopathology, management, and follow-up were reviewed. Diagnostic criteria included inappropriately normal or elevated TSH levels with increased free thyroid hormones and pituitary imaging confirming an adenoma. Remission was defined as clinical and biochemical normalization without ongoing therapy. Subgroup analysis examined the impact of diagnostic delay on tumour size, invasiveness, and outcome. The cohort comprised 9 men (75%) and 3 women (25%) with a mean age at diagnosis of 47.8 ± 17.2 years. Excluding one MEN1 case with early detection, the mean diagnostic delay was 42.5 months (range 4-156). MRI revealed macroadenomas in 75% and Knosp grade 3-4 invasion in 41.7%. Longer diagnostic delay correlated with significantly larger tumours (17.9 ± 3.6 mm vs 9.8 ± 1.0 mm; p = 0.004). All patients underwent surgery; 50% achieved remission, while 33.3% required additional therapy (SSA and/or radiotherapy). At a median 7.8-year follow-up, 66.7% remained in sustained remission. No patient experienced thyroid storm; transient postoperative hypothyroidism occurred in 25%. TSHomas often present with heterogeneous and misleading biochemical profiles leading to diagnostic delay, larger and more invasive tumours, and greater need for multimodal therapy. Early recognition of discordant thyroid function tests-elevated free T3/T4 with non-suppressed TSH-is critical to avoid unnecessary thyroid ablation and to improve surgical outcomes.

Steroidogenesis in the human adrenal cortex follows a distinct anatomical and functional zonation, which is essential for maintaining electrolyte balance, stress response, and metabolic homeostasis. Dysregulation of this tightly controlled system leads to endocrine disorders causing hypertension, such as primary aldosteronism and glucocorticoid excess. The aim of this study was to analyze the zonal distribution and expression levels of enzymes involved in steroidogenesis and correlate these findings with hypertension, body mass index and previous administration of corticosteroids while correcting severe acute respiratory syndrome coronavirus 2 infection as a potential confounder. Tissue microarrays were constructed from 99 formalin-fixed paraffin-embedded adrenal glands obtained from adult human autopsies, with clinical information on hypertension status. As controls, 14 normal adrenal glands derived from surgical specimens were included. Protein expression of CYP11B2, CYP11B1, CYP17, HSD3B1, and HSD3B2 was assessed semi-quantitatively and evaluated with respect to their localization within specific adrenal cortical zones using immunohistochemistry. The expression of CYP17, CYP11B1, CYP11B2, and HSD3B2 was inversely correlated with the presence of hypertension (p<0.001 and p=0.0149), higher body mass index (p=0.026 and p=0.001), and the administration of corticosteroids (p=0.0012, p=0.001, and p=0.002). CYP11B2 showed reduced expression in the zona glomerulosa only in the non-COVID-19 hypertension group (p=0.031). Tissue microarray-based tissue analysis is a reliable method in a research setting to detect consistent downregulation of CYP11B1, CYP11B2, and CYP17 in patients with hypertension, independent of concomitant underlying infections. The positive correlation between the body mass index and CYP11B1 expression, and the negative correlation between glucocorticoid administration and CYP11B1, may reflect clinical factors such as obesity-associated hypertension and altered aldosterone production and its relationship with metabolic syndrome.

Current insulin therapy fails to fully restore physiological glucose homeostasis in type 1 diabetes mellitus, with 75% of patients unable to achieve the desired management targets. While stem cell-derived islets offer promising therapy, they require an enhanced extracellular matrix support for optimal transplantation outcomes. To address this challenge, we developed biofunctional endocrine micro-pancreata using decellularized porcine lung scaffolds seeded with embryonic stem cell-derived islets. In vivo efficacy was evaluated following subcutaneous or intraperitoneal transplantation into NOD-SCID mice, followed by streptozotocin induction of diabetes, with the comprehensive assessment of human insulin secretion, glucose homeostasis, and graft integration over 3 months. Our results demonstrated that endocrine micro-pancreata exhibited 1.4-fold-increased glucose-stimulated insulin secretion in vitro compared to non-responsive free islets. In vivo, endocrine micro-pancreas recipients maintained significantly lower glucose levels than controls throughout the experiment. Subcutaneous endocrine micro-pancreata showed superior performance, with 46% improved glucose tolerance versus 31% improvement for intraperitoneal delivery. Extensive CD31-positive neovascularization as well as insulin staining confirmed successful graft integration and sustained insulin production. Endocrine micro-pancreata provide a scalable platform for diabetes cell therapy, demonstrating sustained insulin secretion and improved glycemic control. The preserved extracellular matrix microenvironment supports islet function and vascularization, offering significant potential for clinical translation.

Type 2 diabetes mellitus affects the quality of life of patients significantly. Traditional treatments have certain limitations; however, cellular therapy has demonstrated remarkable positive effects, such as improved blood glucose and lipid levels, repaired pancreatic and renal structure, and improvements in diabetic complications. A type 2 diabetes mellitus rat model was constructed, and rats were divided into six groups. Four groups were further formed to evaluate the antiinflammatory effects of umbilical cord mesenchymal stem cells. The antiinflammatory effects of human umbilical cord mesenchymal stem cells were demonstrated using inflammatory factors and M2 macrophages, a type of antiinflammatory macrophage. Western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were performed to further elaborate the mechanism of action of human umbilical cord mesenchymal stem cells in type 2 diabetes mellitus treatment. We confirmed that human umbilical cord mesenchymal stem cells could efficiently treat type 2 diabetes mellitus. We conducted an ameliorative fasting blood glucose test and an oral glucose tolerance test and assessed the recovery of liver and renal function using biochemical factors (such as TC, TG, BUN, and Ccr, among others). The antiinflammatory effect of the treatment was demonstrated by the increased expression of biomarkers in M2 macrophages and reduced secretion of inflammatory cytokines, such as TNF-α. The regulatory mechanism was involved in the TLR4/NF-κB signaling pathway. The apoptosis of pancreatic tissues in type 2 diabetes mellitus was also inhibited by umbilical cord mesenchymal stem cells, contributing to relief from type 2 diabetes mellitus symptoms. In conclusion, our findings confirmed that efficient type 2 diabetes mellitus treatment using human umbilical cord mesenchymal stem cells was related to antiinflammatory effects mediated via TLR4/NF-κB signaling inhibition and apoptosis attenuation in pancreatic tissues.

To investigate the clinical features of nivolumab-induced isolated adrenocorticotropin deficiency and to provide a reference for the diagnosis, treatment and rational use of nivolumab, clinical reports of nivolumab induced isolated adrenocorticotropin deficiency were collected by searching the database until August 31, 2025. Clinical data were collected and retrospectively analyzed. Seventy-one patients were enrolled, with a median age of 66 years (range: 26-87), and 73.2% of whom were male and 67.6% from Japan. Melanoma (36.6%) was the main indication for nivolumab. The median time from initiation of nivolumab to the onset of isolated adrenocorticotropin deficiency was 24 weeks (range: 3-60) and the median was 8 cycles (range: 2-33). Fatigue (76.1%), anorexia (66.2%) and nausea (23.9%) were the most common symptoms of isolated adrenocorticotropin deficiency. Laboratory tests revealed hyponatremia (50.7%) and eosinophilia (28.2%). Pituitary magnetic resonance imaging showed no abnormality in most patients (71.8%). Thyroid dysfunction (26.8%) often coexists with isolated adrenocorticotropin deficiency. These patients had a good prognosis after receiving a physiological dose of hydrocortisone. Nivolumab-induced isolated adrenocorticotropin deficiency is a rare disorder with possible racial differences. The possibility of isolated adrenocorticotropin deficiency should be considered in patients with fatigue and fatigue during treatment. Serum sodium and eosinophil ratios should also be closely monitored. The prognosis is good after hydrocortisone replacement therapy.

Exenatide and dapagliflozin are medications commonly used in the controlling of T2DM. We aim to assess the efficacy of the combination of both drugs in the management of diabetes and weight control compared to the efficacy of each drug alone. We investigated four databases for relevant randomized clinical trials RCTs. Then a Network meta-analysis was made on the pertinent studies. Mean differences with 95% confidence intervals (CI) were utilized to pool continuous data, and the Cochrane Tool was employed to assess the quality of the included RCTs. The network meta-analysis was conducted using the R statistical software. We analyzed 837 patients from four studies. The combination had a significant decrease in HbA1c (mmol/L) compared to exenatide and dapagliflozin; [MD: -3.94, 95% (CI, -6.38 to -1.49)], [MD: -6.54, 95% (CI, -8.90 to -4.17)] respectively. Also, the combination showed a significant decrease in weight compared to dapagliflozin and exenatide alone; [MD: -1.07, 95% CI, (-1.76 to -0.39)] and [MD: -1.82, 95% CI, (-2.52 to -1.13)] respectively. The combination of dapagliflozin and exenatide lowers body weight, glycated hemoglobin, and blood pressure more effectively than any of the drugs alone. We suggest that this combination, according to its efficacy in improving the primary outcomes of diabetes, will result in general improvement of symptoms and decrease in complications.

Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms. Targeting NETs in the elderly as an anti-aging therapy seems to be a very attractive therapeutic approach. Therapeutic apheresis with a specific filter to remove NETs could be a promising strategy worth considering.