Endocrine Connections最新文献

Background and aims: This study aimed to explore whether a younger age of diabetes onset is associated with an increased risk of CVD events.

Methods: This study included 621 patients with younger-onset T2DM (age, ≤50 years) and 573 with older-onset T2DM (age, >50 years) from the original Da Qing Diabetes Prevention Study. For comparison, 310 younger individuals without diabetes (age, ≤50 years) were included in the control group. We followed up participants for 34 years to assess the incidence of CVD events. The association between the age of diabetes onset and the risk of CVD events was analysed.

Results: The younger-onset T2DM patients had a higher incidence of components of CVD events per 1,000 person-years than those of the older-onset T2DM and younger non-diabetes controls (19.20, 15.14, and 9.22 for stroke, 7.78, 4.67, and 2.15 for myocardial infarction, and 5.38, 2.76, and 1.11 for heart failure, respectively). The more than double high risk of composite CVD events was found in the younger-onset T2DM compared with the older-onset T2DM (HR = 2.05, 95% CI: 1.64-2.55) and non-diabetic controls (HR = 3.45, 95% CI: 2.39-4.98) even after adjusting for the strongest confounder diabetes duration.

Conclusions: Chinese adults with younger-onset T2DM have a higher risk of developing CVD events than those with older-onset T2DM over a 34-year follow-up period.

Aims: Chemotherapy regimens can induce severe hyperglycemia, which may be underestimated using conventional point-of-care blood glucose (POC-G) measurement techniques. Real-time continuous glucose monitoring (rtCGM) systems may offer a more accurate assessment of glucose metabolism. In this study, we compared blood glucose monitoring using POC-G and rtCGM in patients with rare endocrine cancers caused by chemotherapy and steroid medication.

Methods: In this single-center observational study, we analyzed data from 76 hospitalized patients with pancreatic neuroendocrine tumors (n = 48) or adrenocortical carcinoma (n = 28) undergoing chemotherapy. Patients were monitored using either POC-G (n = 38) or rtCGM (n = 38). Glycemic metrics included time in range (TIR), prevalence of steroid-induced hyperglycemia (SIH), and HbA1c.

Results: Using POC-G, TIR was 23.6 ± 0.9 h/day in patients without diabetes (NoD) and 20.0 ± 4.2 h/day in patients with diabetes undergoing chemotherapy (mean: five cycles). However, when rtCGM was used, drastic changes in TIR were documented under the same regimen. The mean TIR decreased from 21.7 h/day in patients with NoD to 14.6 h/day in patients with diabetes (P < 0.01). Similarly, the overall incidence of SIH was 30% using conventional POC monitoring, but this figure rose to 79% using rtCGM. During rtCGM use, HbA1c decreased by 0.3% over the course of the chemotherapy cycles, whereas during POC-G use, HbA1c increased by 0.2% (P < 0.01).

Conclusion: We demonstrated a previously underestimated frequency of hyperglycemia and SIH in patients undergoing chemotherapy by using rtCGM. The use of rtCGM enabled more detailed recognition of dysglycemia and may improve glucose metabolism during and after chemotherapy regimens.

Objective: This study investigates the utilization of modern glucocorticoid medications (Acecort®, Alkindi®, Efmody®, Plenadren®) for congenital adrenal hyperplasia due to 21-hydroxylase deficiency, examining prescribing patterns, barriers to adoption, and geographical and temporal trends.

Methods: A two-part study was conducted: a retrospective analysis of treatment regimens from the International Congenital Adrenal Hyperplasia Registry across 46 centres in 20 countries (2017-2023), and a qualitative survey of 39 centres regarding barriers to prescribing modern medications. Patients included both paediatric and adult populations. Data analysed included regional prescription trends, timing of modern glucocorticoid adoption, and identified barriers.

Results: From 2017-2023, 44 of 790 (5%) patients transitioned from traditional to modern glucocorticoid therapy, with the highest adoption in high-income Western European countries. Alkindi® was exclusively prescribed to patients under 8 years, while 97% of Efmody® users were 7 years or older. By 2023, modern glucocorticoid availability varied among centres: Alkindi® (54%), Efmody® (46%), Plenadren® (33%), and Acecort® (15%).

Conclusion: Adoption of modern glucocorticoid medications for congenital adrenal hyperplasia remains limited, with only approximately 5% of patients transitioning from traditional therapies. Significant barriers include legislative approval, supply chain challenges, and elevated costs.

Plain language summary: This international study looked at how new medications for congenital adrenal hyperplasia are used globally. We found that despite increasing availability of new medications during the study time period, only a small number of patients (5%) switched to these newer treatments. This limited use is mainly due to high costs, problems with getting legal approval, and supply issues, highlighting unequal access to care worldwide.

Objective: To establish sex- and age-specific reference intervals for plasma concentrations of adrenocorticotropic hormone (ACTH) and direct renin in healthy youth.

Design: 529 healthy subjects (5.8-20.4 years) were recruited as part of the third Copenhagen Puberty Study, an ongoing cross-sectional study of healthy Danish participants attending compulsory school and high school.

Method: Plasma ACTH and direct plasma renin concentrations were established using GAMLSS statistics, sex- and age-specific reference intervals and standard deviation (SD) scores. Concentrations were evaluated according to pubertal stage and oral contraceptive (OC) use.

Results: ACTH concentrations did not differ between sexes. ACTH concentrations were higher in pubertal males than in prepubertal males (P = 0.015); however, this difference was not statistically significant when analyses were restricted to samples collected before 10:00 h. In females, ACTH concentrations did not seem to differ according to pubertal status. In both sexes, renin concentrations were lower in pubertal than in prepubertal subjects (females: P < 0.001; males: P = 0.016). Renin SD scores were lower in OC users than in non-OC users (P = 0.007), while ACTH SD scores did not differ between these groups.

Conclusion: Sex- and age-specific reference intervals for plasma concentrations of ACTH and direct renin in young, healthy subjects were provided, reflecting changed levels through puberty and significantly lower renin SD scores in OC users. Application of these biomarkers' SD scores may enhance the management of patients with adrenal disorders.

Significance statement: Reliable reference data for plasma ACTH and direct plasma renin in healthy children are limited. This large population-based cohort study of healthy participants attending compulsory school and high school provides comprehensive sex- and age-specific reference intervals for plasma ACTH and renin. Furthermore, absolute concentrations were converted to relative SD scores, thereby providing a more unified and standardized tool for clinical assessment. Reporting ACTH and renin concentrations by pubertal stage represents a novel aspect. These new reference intervals enhance the clinical utility of biomarker-based monitoring and treatment of pediatric endocrine disorders, such as congenital adrenal hyperplasia, addressing a critical gap in current clinical pediatric practice.

Clinical trial registration number: NCT04884620.

Background: Non-metastatic pheochromocytomas and paragangliomas (PPGLs) are considered a curable cause of secondary hypertension. However, some studies identified that a considerable ratio of patients (10.0-43.8%) still experience persistent hypertension even after successful resection of PPGLs.

Methods: We conducted a retrospective analysis of 472 PPGL patients who underwent surgical resection at three centers from January 1, 2012, to October 31, 2022. Comprehensive clinical data were recorded. Binary unconditional logistic analysis was conducted to identify the independent variables associated with long-term persistent hypertension.

Results: The cohort had an average age of 50.5 years, and the median follow-up duration was 61 months. A total of 26.3% of PPGL patients experienced long-term persistent hypertension. After multivariate analysis, we identified older age (odds ratio (OR): 1.021, P = 0.008), higher body mass index (BMI, OR: 1.088, P = 0.004), lower left ventricular ejection fraction (LVEF, OR: 3.506, P = 0.006), and developed intraoperative hemodynamic instability (HDI, OR: 2.053, P = 0.002) as independent risk factors for long-term persistent hypertension in PPGL patients.

Conclusion: This study demonstrated that nearly a quarter of PPGL patients still suffer from persistent hypertension after successful resection and identified several risk factors, such as older age, higher BMI, lower LVEF, and developed intraoperative HDI. These results might contribute to improving long-term follow-up strategies.

Background: This study aimed to investigate the effects of miR-451 on proliferation, invasion, and migration of the papillary thyroid carcinoma (PTC) cell line TPC-1, focusing on its regulatory role in the PI3K/AKT/mTOR signaling pathway.

Methods: TPC-1 cells were transfected with siRNA-NC, miR-451 mimic, or miR-451 inhibitor and treated with the PI3K activator 740Y-P (miR-451 mimic + 740Y-P) where indicated. Cell proliferation, migration, and invasion were assessed using MTT, wound healing, and transwell assays, respectively. Protein expression and pathway activation were analyzed by western blot.

Results: Compared to the blank and siRNA-NC groups, the miR-451 mimic group showed significantly lower expression of Bcl-2, p-PI3K, p-AKT, and p-mTOR proteins, along with significantly higher expression of Bax (P < 0.05). Conversely, the miR-451 inhibitor group exhibited significantly elevated levels of Bcl-2, p-PI3K, p-AKT, and p-mTOR and significantly reduced Bax expression (P < 0.05). Furthermore, compared with the miR-451 mimic group, the miR-451 mimic + 740Y-P group displayed significantly increased expression of Bcl-2, p-PI3K, p-AKT, and p-mTOR, along with significantly decreased Bax levels (P < 0.05).

Conclusions: miR-451 expression is significantly reduced in PTC tissues and TPC-1 cells. Overexpression of miR-451 inhibits proliferation, invasion, and migration in TPC-1 cells, likely via the PI3K/AKT/mTOR signaling pathway, suggesting its potential as a molecular target for further investigation in PTC.

Introduction: Estradiol may influence sleep-wake rhythms via modulation of the circadian timing system, but evidence is limited and often based on small samples. This study examined associations between serum estradiol levels and sleep parameters in men and in pre- and postmenopausal women from the general population.

Methods: This cross-sectional analysis used baseline data from the Netherlands Epidemiology of Obesity (NEO) study. Estradiol was measured in fasting serum using LC-MS/MS. Sleep quality and timing were assessed with the Pittsburgh Sleep Quality Index (PSQI). Associations were evaluated using multivariable weighted linear regression.

Results: Among 4,754 participants (51% men; mean age 56 years), serum estradiol levels were not associated with sleep quality or timing. Participants in the highest 10th percentile of estradiol showed marginally better sleep quality compared with those in the middle range (difference in PSQI = -0.74; 95% CI -1.11 to -0.36).

Discussion: These findings suggest that, under physiological conditions, estradiol levels are not clearly linked to sleep quality or timing.

Background: Currently, there is very limited information on referral patterns, diagnostic work-up, and management of adrenal tumours across secondary and tertiary endocrine centres in the UK.

Objective: To evaluate current practices in assessing and managing adrenal tumours across the UK, including diagnostic pathways and adherence to international guidelines on screening of patients with newly diagnosed adrenal tumours.

Methods: A 12-item web-based survey was distributed to members of the UK Society for Endocrinology (approximately 1,600 contacts), capturing centre characteristics, number of patients with adrenal tumours and diagnostic strategies.

Results: Eighty-five responses representing 80 centres were analysed. Over 45% of respondents, mainly from tertiary centres, reported more than 100 annual referrals. Malignancy rates were <5% in 89.5% of centres. Nearly all centres (99.8%) reported full or partial adherence to 2023 ESE-ENSAT guidelines. However, only 55% held regular adrenal-specific multidisciplinary meetings, and 24% reported referral-to-diagnosis times exceeding six months. Steroid profiling (urinary or serum) was incorporated into diagnostic work-up by 71.8% of centres.

Conclusions: This survey provides the first national overview of adrenal tumour management pathways in the UK. Findings highlight strong guideline adherence but variability in multidisciplinary practice and diagnostic timelines. These data offer a foundation for policy development and future research, particularly as increasing incidental detections from cross-sectional imaging place growing demands on NHS resources.

Objective: To determine the prevalence and clinical impact of rhabdomyolysis (RML) among adults hospitalized with diabetic ketosis.

Design: Ten-year retrospective single-center cohort study.

Methods: We reviewed adults admitted with diabetic ketosis, including isolated ketosis and diabetic ketoacidosis (2015-2024). RML was defined as peak creatine kinase >1,000 U/L; patients with confirmed acute myocardial infarction were excluded. The primary endpoint was a composite poor outcome, defined as in-hospital death or discharge against medical advice (DAMA) due to critical illness with a grave prognosis. Predictors of poor outcome were assessed using Firth-corrected multivariable logistic regression.

Results: Of 920 eligible patients, 18 (1.96%) developed RML. Compared with controls, patients with RML were older and more likely to have neurological comorbidities, recent falls, impaired consciousness, infection, effective serum osmolality >320 mOsm/kg, leukocytosis, higher C-reactive protein, elevated creatinine, acute kidney injury, markedly raised myoglobin, and elevated troponin I. RML was associated with a longer hospital stay, higher costs, a higher in-hospital mortality (11.1 vs 0.67%), and a higher rate of the composite poor outcome (16.7 vs 1.11%). Leukocytosis (>9.5 × 109/L; adjusted OR: 4.29, 95% CI: 1.35-14.37, P = 0.014) and troponin I > 0.03 ng/mL (adjusted OR: 5.79, 95% CI: 1.56-21.86, P = 0.009) independently predicted poor outcome.

Conclusions: RML is an uncommon but important complication of diabetic ketosis, conferring a higher short-term mortality, healthcare use, and composite poor outcome. Routine screening for RML and concurrent inflammatory or cardiac injury provides a crucial window for early risk stratification, enabling clinicians to optimize therapeutic strategies and resource use for high-risk individuals.