Endocrine Connections最新文献

Objective: This study aims to identify potential drugs associated with diabetes insipidus (DI) and track its epidemiological characteristics using the FDA Adverse Event Reporting System (FAERS) database.

Methods: A retrospective pharmacovigilance analysis was conducted on FAERS data from Q1 2004 to Q4 2024. Disproportionality analyses were performed using the reporting odds ratio and the Bayesian confidence propagation neural network (BCPNN).

Results: A total of 2,189 cases of DI were recorded in FAERS, with a median age of 47.0 years (interquartile range (IQR) 27.0-60.0). Disproportionality analysis identified 71 drugs with positive signals, in which nervous system agents (22 drugs, 31.0%), antineoplastic agents (15 drugs, 21.1%), and systemic anti-infectives (14 drugs, 19.7%) constituted the top three drug classes. Lithium (n = 114, information component at the 95% lower credibility interval (IC025) = 6.12) and dexmedetomidine (n = 105, IC025 = 6.79) were identified as the most frequently reported drugs and showed the strongest association with DI. Several drugs, such as aripiprazole, letrozole, tigecycline, and dapagliflozin, were found to have unexpected potential associations with DI.

Conclusion: This study provides a comprehensive overview of drug-induced DI based on real-world data. It highlights the importance of monitoring patients for DI when using certain medications, particularly high-risk nervous system drugs and antineoplastic agents.

Background: This study investigates glucose metabolism changes in CG-IUGR rats and analyzes the potential underlying mechanisms. It identifies a critical warning period for glucose metabolism changes in CG-IUGR individuals from birth to adulthood, providing key intervention targets for the prevention and treatment of diabetes.

Methods: The CG-IUGR rat model was established by a low-calorie diet during pregnancy. Rats were measured weekly after birth for body length, weight, and BMI. Rats were assayed at 8-week-old for the following indicators. Serum fasting insulin (FINS) and insulin levels at 15 min after glucose load were detected. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were carried out. Skeletal muscle/liver glycogen content, glycogen synthase (GS) expression, and GS activity were assessed before and after glucose load.

Results: BMI and perirenal fat weight were significantly increased in CG-IUGR rats, showing catch-up growth. Serum FINS was decreased, whereas insulin at 15 min after glucose load was increased in CG-IUGR rats. GTT and ITT showed that CG-IUGR rats had significantly higher blood glucose levels at each time point after 15 min administration, suggesting their glucose intolerance and reduced insulin sensitivity. CG-IUGR rats manifested diminished skeletal muscle and liver glycogen content under basal conditions, accompanied by reduced GS expression and activity in these tissues. However, following a 15 min glucose challenge, a contrary trend was observed for all three parameters.

Conclusions: CG-IUGR rats have an increased susceptibility to DM. IUGR remodels glycogen synthesis in CG-IUGR rats, as demonstrated by the preferential storage of energy as glycogen.

Background: Maternal thyroid hormones have been shown to affect neonatal thyroid function. However, it remains unclear whether these associations persist across trimesters, and also little is known regarding the potential effects of mixtures.

Objective: This study aimed to examine the effects of maternal thyroid hormones as individual and as mixtures across three trimesters on neonatal thyroid stimulating hormone (TSH).

Methods: We included 2,139 pregnant women. Maternal thyroid hormones (TSH, free triiodothyronine (FT3), and free thyroxine (FT4)) across three trimesters and neonatal TSH level were measured. Multivariable linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations between maternal thyroid hormones (individual and mixtures) across three trimesters and neonatal TSH.

Results: Maternal TSH demonstrated the positive associations with neonatal TSH across three trimesters (first trimester: β = 0.112; 95% CI: 0.008, 0.215; second trimester: β = 0.122; 95% CI: 0.032, 0.212; third trimester: β = 0.115; 95% CI: 0.031, 0.200). Neonatal TSH was also positively associated with maternal FT4 in the third trimester (β = 1.313; 95% CI: 0.367, 2.239). Moreover, we found sex-specific associations, and the positive associations of maternal TSH and FT4 with neonatal TSH in the third trimester were observed only among female infants, while the positive association of maternal TSH with neonatal TSH in the second trimester was observed only among male infants. The overall positive associations of the mixtures were observed, and maternal TSH was identified as the major contributor.

Conclusion: Maternal thyroid hormones affect neonatal thyroid function across all three trimesters by fetal sex.

Objective: To investigate the clinicopathological correlation, prognostic significance, and risk model of SDHB expression loss and ERBB2 expression in pheochromocytomas and paragangliomas (PPGLs).

Methods: A total of 165 patients with histologically confirmed PPGLs who underwent surgery at the Cancer Hospital were enrolled. Clinical and pathological characteristics were retrospectively analyzed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) methods were employed, and data were analyzed and visualized using SPSS 25.0 and R Studio.

Results: Among the 165 patients (male-to-female ratio: 0.85:1; age range: 14-82 years), there were 117 cases of pheochromocytomas and 48 cases of paragangliomas. SDHB expression loss was detected in 29 patients, and SDHB expression retention was observed in 136 patients. ERBB2 overexpression was found in 47 patients and absent in 118 patients. A statistically significant correlation was observed between SDHB expression loss and ERBB2 expression (P < 0.001, R = 0.45). Survival analysis revealed significant differences in progression-free survival (P < 0.001) and overall survival (P < 0.001) between SDHB expression loss and SDHB expression retention PPGLs, as well as between ERBB2-overexpressing and low/non-expressing groups (PFS: P < 0.001; OS: P = 0.01). Univariate and multivariate COX regression analyses showed that SDHB expression loss was an independent prognostic factor for PFS. A three-tier risk prediction model based on four risk factors was established, with 5-year PFS rates of 91.5%, 41.7%, and 34.8% for low-risk, intermediate-risk, and high-risk groups, respectively (P < 0.001).

Conclusion: SDHB expression loss and ERBB2 overexpression are adverse prognostic factors in PPGL patients, and there may be a potential link between them. In addition, the risk prediction model established in this study confirms its predictive value for risk stratification in PPGL patients.

Significance statement: Studies on the correlation between SDHB expression loss and ERBB2 expression in PPGLs are still in a black stage, and a consensus on risk assessment for PPGL patients has not been reached. Therefore, these two aspects are the key objectives of our research. We investigated SDHB expression loss and ERBB2 expression at the protein level, exploring the correlation between them, conducting prognostic analysis, and establishing a risk model, in order to provide new diagnostic and therapeutic ideas and data support for the clinical management of PPGL patients.

Elabela (ELA) is a relatively newly identified bioactive micropeptide that functions as the second endogenous ligand for the apelin receptor (APJ). It plays a critical role in diverse physiological processes, including cardiovascular development, blood pressure regulation, and fluid homeostasis. Growing evidence underscores its significance in the pathophysiology of various organ systems, particularly the kidneys. This review aims to comprehensively explore the role of ELA in renal physiology and pathology. We focus on its molecular mechanisms, such as modulating renal hemodynamics, inhibiting fibrosis and inflammation, promoting cellular survival, and its therapeutic potential in acute kidney injury, chronic kidney disease, and hypertensive and diabetic nephropathy. Building upon our research group's previous work, this article places special emphasis on the role of ELA in renal metabolism and its promising application in the treatment of diabetic kidney disease. By synthesizing recent advancements, we seek to elucidate the connection between ELA and kidney health, assessing its potential as a novel therapeutic target for renal diseases.

Purpose: Steroidogenic factor 1 (SF-1), encoded by NR5A1, is essential for spleen development and function. NR5A1 variants have been linked to abnormal spleen development. Hyposplenism exposes individuals to severe complications with potentially serious sequelae. This study aimed to determine the prevalence and principal features of hyposplenism in a cohort of French patients with NR5A1 variants.

Methods: We conducted a cross-sectional multicentre ancillary study among 34 patients carrying heterozygous NR5A1 variants within the GR-EX cohort, which includes individuals from families affected by red blood cell diseases. All participants underwent splenic imaging (ultrasound, CT, or MRI) and pocked red blood cell (pRBC) quantification. pRBC thresholds of <7%, 7-20%, and >20% corresponded to normal splenic function, moderate hyposplenism, and severe hyposplenism, respectively. The primary endpoints were the prevalence of hyposplenism and its severity.

Results: Functional hyposplenism was observed in 21/34 patients (61.7%), including 16/34 (47%) with severe forms. Morphological spleen abnormalities were identified in 15/34 patients (44.1%), with asplenia in 4/34 (11.7%). All patients with morphological spleen abnormalities on imaging also presented functional hyposplenism. Conversely, 6/21 patients (28%) with functional hyposplenism showed no morphological abnormalities on imaging. No association was found between NR5A1 genotypes, gonadal phenotypes, and splenic anomalies.

Conclusions: Functional hyposplenism was frequent in this cohort of patients carrying NR5A1 variants, regardless of genotype and gonadal phenotype. Assessing splenic function is mandatory to help manage these patients. Preventive measures are also critical when hyposplenism is present.

The menopause transition represents a period of complex hormonal, metabolic, and psychosocial change that poses unique challenges for women living with type 1 diabetes mellitus (T1DM). Despite an expanding population of midlife women with T1DM, evidence to guide optimal menopause management remains limited. This narrative review synthesises current clinical and mechanistic evidence on the impact of menopause in women with T1DM. A literature search was conducted in MEDLINE (PubMed), the Cochrane Library, and professional society guidelines between January and May 2025. Across studies, women with T1DM appear to experience an earlier onset of menopause and an increased risk of osteoporosis, cardiovascular disease, psychological distress, metabolic deterioration and sexual dysfunction compared with women without diabetes. Oestrogen deficiency may exacerbate insulin resistance, dyslipidaemia, and vascular dysfunction, while glycaemic variability and altered insulin requirements are frequently reported during the menopause transition. Evidence regarding the safety and efficacy of hormone replacement therapy (HRT) in this group is sparse. In the absence of disease-specific data, clinicians should adopt an individualised approach - screening proactively for menopausal symptoms, bone loss, and cardiovascular risk, tailoring HRT decisions based on individualised risk profiles, and recommending transdermal oestradiol when HRT is used. This review highlights the urgent need for dedicated research, evidence-based guidelines, and integrated clinical pathways to optimise menopause management and long-term outcomes for women living with T1DM.

The world population is ageing. According to projections of the World Health Organisation, it is expected that between 2020 and 2050, the number of people aged 60 years and older will double to reach 2.1 billion worldwide, while the number of persons aged 80 years or older is expected to triple to reach 426 million worldwide. Thyroid dysfunction is common in older populations and comes with specific challenges regarding its diagnosis and management. In older populations, overt hypothyroidism and hyperthyroidism often present differently and with fewer symptoms. This may be due to confounding by the higher presence of comorbidities and polypharmacy, but also because of age-related differences in underlying disease aetiology. While autoimmunity remains the main cause of thyroid disease in older populations, thyroid autonomy contributes significantly to hyperthyroidism in older populations. The serum TSH distribution displays a shift toward higher concentrations in older populations, resulting in a higher prevalence of (biochemically defined) subclinical hypothyroidism. Concurrently, age-related differences in body composition and physiology may cause changes in the absorption, distribution, and clearance of drugs, resulting in slower drug metabolism. Management of thyroid dysfunction in older populations requires careful diagnosis, gradual treatment, and lifelong follow-up, as older people are at increased risk of undertreatment and overtreatment.

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Abstract: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis. The GnRH stimulation test remains the diagnostic gold standard, especially in girls with undetectable basal LH levels. However, native GnRH is expensive and often unavailable. Rapid-acting subcutaneous triptorelin has been proposed as a reliable alternative. This retrospective study evaluated the diagnostic accuracy of subcutaneous triptorelin compared with intravenous gonadorelin and investigated the optimal timing for LH peak assessment. A total of 341 girls referred for suspected precocious puberty were evaluated: 102 underwent the triptorelin test and 239 the gonadorelin test, with gonadotropins measured by electrochemiluminescence assay at baseline and after stimulation. Based on clinical, radiological, and laboratory criteria, 143 girls were diagnosed with CPP and 198 with non-progressive thelarche (NPT). Triptorelin elicited significantly higher FSH peaks than gonadorelin, while LH peaks were comparable; consequently, FSH/LH ratios were higher after triptorelin. ROC analysis identified an optimal diagnostic LH peak cut-off of 7.14 IU/L following triptorelin administration (sensitivity 94%, specificity 96%; AUC 0.985), while a threshold of 4.7 IU/L was observed after gonadorelin (sensitivity 100%, specificity 87%; AUC 0.982). Peak LH occurred predominantly at 180 min after triptorelin in both CPP and NPT groups (78 and 90%, respectively). Despite the limitations of its retrospective and non-parallel design, this large cohort study demonstrates that subcutaneous triptorelin provides excellent diagnostic accuracy, comparable to gonadorelin. These findings support triptorelin as a reliable and accessible alternative for CPP diagnosis and contribute to the standardization of diagnostic protocols in clinical practice.

Plain language summary: This study tested triptorelin stimulation as an alternative to the standard gonadorelin test to diagnose precocious puberty in girls. Triptorelin proved equally accurate and reliable, especially when hormone levels are measured 3 h after injection, offering a practical diagnostic tool in clinical practice.

This retrospective study aimed to identify and characterize signals of ocular adverse events (AEs) related to bisphosphonates (BPs) using FDA adverse event reporting system (FAERS) data (Q1 2004 to Q3 2024) to inform future safety investigations. Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods to identify BP-related ocular AE signals. In addition, a modified ROR method was utilized to examine differences across gender and age. Among 6,965 ocular AE reports for five BPs (alendronate, zoledronate, pamidronate, risedronate, and ibandronate), 136 positive signals were identified, predominantly unlisted in drug labels. Notable risks included ocular inflammatory AEs (especially zoledronate) and novel risk signals such as cataract, glaucoma, and macular degeneration. Standardized MedDRA queries (SMQ) linked BPs to 11 eye disorders, with scleral disorders common to all five BPs and pamidronate involving the broadest SMQ categories. Ocular AEs for alendronate, zoledronate, and pamidronate exhibited age-related differences, while those for alendronate and zoledronate showed gender differences. This study identifies high-risk and novel ocular AEs related to BPs. These findings warrant further validation in future studies.