European Journal of Endocrinology最新文献

Objective: Evidence on the duration of post-operative adrenal insufficiency (AI) in patients with endogenous hypercortisolism is scarce. We sought to determine the duration of post-operative AI and to identify factors associated with the duration of AI in patients undergoing surgery for endogenous hypercortisolism.

Methods: We conducted a single-center prospective cohort study, 2019-2025, of patients with endogenous hypercortisolism [Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)] treated with surgery. Associations of demographics, body mass index (BMI), clinical, and biochemical hypercortisolism severity, subtype of hypercortisolism, pre-surgical hypercortisolism duration, glucocorticoid type, and nadir cortisol in relation to duration of AI were investigated.

Results: The 242 patients [41% MACS, 46% pituitary CS, 12% adrenal CS, 1% ectopic CS, median age 50 years (IQR: 40-60), 85% women] who developed postsurgical AI were followed for a median duration of 13.7 months (IQR 7.2-26.3). The median time to recovery of AI was shorter in MACS vs. overt CS (3.9 months (95% CI: 3.3-6.2) vs. 13.5 months (95% CI 11.3-18.3), P value < .001). On multivariable analysis adjusting for age, sex, BMI, and glucocorticoid type, moderate to severe biochemical severity score (β = 11, P value < .001) and moderate to severe clinical severity score (β=8.7, P < .001), were associated with a longer duration of AI.

Conclusions: Baseline clinical and biochemical hypercortisolism severity scores may inform individualized counseling on post-operative AI duration in patients treated for CS and MACS.

Background: Primary aldosteronism (PA) is characterized by autonomous aldosterone production, which leads to left ventricular (LV) remodeling and adverse cardiovascular outcomes. This meta-analysis aimed to compare the effects of two treatment strategies, mineralocorticoid receptor antagonists (MRAs) and adrenalectomy, on the regression of LV remodeling in patients with PA.

Methods: Embase, PubMed, and Cochrane Library were searched for studies reporting the effect of adrenalectomy or medical therapy on reversing LV mass index (LVMI) in patients with PA. The outcome of interest was the reduction in LVMI after treatment.

Results: A total of 1197 patients with PA from 10 studies were included in the analysis. The meta-analysis demonstrated that both adrenalectomy and MRAs improved LVMI in patients with PA (adrenalectomy: standardized mean difference [SMD] = -0.49, 95% CI = -0.65 to -0.33; MRAs: SMD = -0.35, 95% CI = -0.48 to -0.22). The reduction in LVMI was greater following adrenalectomy in direct comparison analyses (difference-in-differences SMD = -0.15, 95% CI = -0.26 to -0.03). However, the effect size was small, and the impact of MRA optimization could not be assessed. In studies focusing specifically on unilateral PA, adrenalectomy demonstrated greater LVMI reduction than MRAs.

Conclusions: This meta-analysis suggests that both adrenalectomy and MRAs improve LV remodeling. Although adrenalectomy was generally associated with slightly greater LVMI reductions than MRAs, the impact of optimized MRA therapy on LVMI reduction remains uncertain. When focusing specifically on patients with unilateral PA, adrenalectomy was associated with more pronounced regression of LV remodeling compared with MRA therapy.

Obesity is highly prevalent among women during the menopausal transition, yet current guidelines still offer limited direction on how to address it in this context. In this Letter, we emphasize the need to incorporate obesity assessment and treatment into menopause care. Obesity worsens vasomotor and genitourinary symptoms and alters the risk profile of menopausal hormone therapy, particularly increasing thromboembolic risk with oral formulations. A more integrated approach-combining hormone therapy with obesity management strategies-could improve metabolic outcomes, relieve symptoms, and lower long-term cardiovascular and oncologic risks. Future guidelines should explicitly address this overlap to support more individualized care for women in midlife.

Objective: Distress, fear of progression (FOP), and depression are common in cancer patients and negatively impact patients' health-related quality of life (HRQOL). However, no studies have explored these aspects in adrenocortical carcinoma (ACC), yet.

Methods: We conducted a single-centre observational study in adults (≥18 years) with ACC. We analysed questionnaires addressing FOP, distress (National Comprehensive Cancer Network distress thermometer), depression (patient health questionnaire, PHQ-9), and HRQOL (EORTC-QLQ-C30). Potentially influencing factors were evaluated. Multiple linear regression on HRQOL subscales was performed to identify associated psychosomatic correlations.

Results: Within 12 months, 105 patients were included (56.2% female; median age 49 years, 14.3% newly diagnosed, 46.7% tumour-free, 39.0% metastatic). The majority experienced an elevated level of distress (62%) and of FOP (59%). PHQ-9 results suggested major depression in 41%. Of note, these results were neither influenced significantly by tumour burden, hormone excess nor by cancer treatment. Patients reported moderate functioning scores (median 62.2) and moderate symptom burden (median 33.3) in the EORTC-QLQ-C30. Fatigue and insomnia were prominent symptoms. Tumour burden and treatment affected functioning and symptoms, with significant differences in appetite loss, diarrhoea, nausea, vomiting, and financial difficulties. Hormone excess showed no significant impact on these measures. Our questionnaires indicated a need for psychosomatic counselling in 80% of patients.

Conclusions: Patients with ACC show high values for distress, FOP, and depression, which can only partly be explained by clinical characteristics. Our study suggests that psychosomatic support should be offered to all patients with ACC.

Background: Cardiovascular disease (CVD) risk factors are prevalent in women with polycystic ovary syndrome (PCOS), but prospective data regarding CVD in population-based cohorts are limited.

Aim: This study aims to investigate prospective risk of CVD in Nordic women with PCOS.

Design: This is a national register-based study in women with PCOS and age-matched controls originating from Denmark (PCOS Denmark, N = 27 298, controls, N = 135 019), Finland (PCOS Finland, N = 20 765, controls, N = 59 122), and Sweden (PCOS Sweden, N = 79 454, controls, N = 393 669). The main study outcome was CVD. Cardiovascular disease was defined according to ICD-10 diagnostic codes for major adverse cardiac events, pulmonary embolism, and/or deep venous thrombosis. Cox regression analyses estimated hazard ratio (HR) with 95% CI and adjusted analyses included body mass index (BMI) and education.

Results: The median age at cohort entry was 28 years (Denmark) and 29 years (Finland and Sweden) and the median follow-up time was 8.0-10.0 years. The unadjusted HR (95% CI) for CVD in women with PCOS was 1.30 (1.20; 1.41) in Denmark, 1.45 (1.31; 1.60) in Finland, and 1.52 (1.44; 1.60) in Sweden. Models remained significant after adjusting for obesity and level of education. In a combined meta-analysis including all countries (PCOS, N = 127 517, controls, N = 587 810), the adjusted HR for CVD in women with PCOS was 1.32 (1.25; 1.39). In women with BMI < 25 kg/m2 and no type 2 diabetes, the adjusted HR for CVD risk was 1.40 (1.26; 1.55).

Conclusion: The risk of CVD was increased in women with PCOS across the 3 Nordic countries, also among women with BMI < 25 kg/m2.

Context: Germline CACNA1H mutations have been associated with primary aldosteronism (PA). Here, we described 3 newly discovered CACNA1H variants and explored the possible pathogenic mechanisms as well as therapeutic strategies.

Design: Targeted next-generation sequencing of 10 PA causative genes was performed in 305 PA patients. Variants with possible clinical significance in CACNA1H were identified. Functional analysis was performed in vitro including electrophysiology, steroid hormone production, and transcriptome. Responses to mibefradil and nifedipine were evaluated.

Results: We described 3 heterozygous germline CACNA1H variants (E282K, V213M, and S1249R) in 4 independent cases of PA. Recurrent E282K mutation was identified in 1 patient with severe early-onset PA and 1 patient with bilateral adrenal hyperplasia (BAH). Electrophysiological analysis of mutant Cav3.2 channels revealed significant gain-of-function changes in the voltage-dependent activation and Ca2+ current properties for Cav3.2E282K, while ambiguous for Cav3.2S1249R and Cav3.2V213M. Moreover, stable expression of the 3 CACNA1H variants in H295R cells led to increased aldosterone production and upregulated expression of genes involved in steroidogenic enzymes, both basally and after K+ treatment. T-type calcium channel blocker showed more significant inhibition of aldosterone production in mutant Cav3.2 cells compared to L-type calcium channel blocker.

Conclusions: Our study suggests that Cav3.2E282K is a gain-of-function mutation and T-type calcium channel blockers may be efficient in controlling aldosterone levels for PA patients carrying mutant Cav3.2.