Hormone and Metabolic Research最新文献

Shift work causes a disruption between the circadian system and the external light-dark cycle, but also a misalignment between various levels of the circadian system. There is no information on patients with adrenal insufficiency (AI) who are working shifts. The objective of the study was to analyze the hormone replacement therapy with hydrocortisone (HC) and the adaptation scheme in patients with AI on shifts. Patients working on shifts (n=15) from two German endocrine centers received a questionnaire regarding their therapy scheme, dose adaptations, working shifts, dose adaptations during working shifts, and occurrence of adrenal crisis. We observed that 20% of patients stated that they experience difficulties taking glucocorticoid replacement on time, 40% of patients reported these difficulties to occur only occasionally. Consequently, nearly half of the patients had forgotten to take their replacement therapy at some point. More than 50% of patients reported an adrenal crisis during the last two years. The timely adaptation of HC or of modified-release HC during shifts was very inhomogeneous. In conclusion, the adaptation schemes for HC dosing during shift work are currently not evidence-based but opinion-driven. Our findings highlight the need for further investigations of shift workers with AI.

The triglyceride glucose (TyG) index is used to assess insulin resistance, which is associated with the occurrence and development of cardiovascular diseases, but the risk of carotid plaques is controversial in Asia. We searched PubMed, Embase, Scopus, and Cochrane Library for articles published up to October 15, 2023, to assess the association and dose-response association of the TyG index with the risk of carotid plaques in Asia. The random effects model was used to calculate the effect estimates and 95% confidence intervals (CIs). A total of 534 articles were retrieved, and eleven studies were selected, involving 145 218 Asian participants. When the TyG index was analyzed as a categorical variable, compared with the low TyG index, the high TyG index increased the risk of carotid plaques (OR=1.38, 95% CI: 1.20, 1.60, p<0.001). As continuous variables were analyzed, similar results were observed (OR=1.33, 95% CI: 1.22, 1.45, p<0.001). Meanwhile, dose-response analysis showed that the risk of carotid plaque increased by 1.03 times for every unit increase in the TyG index (RR=1.03, 95% CI: 1.02, 1.03, p<0.001). Our meta-analysis indicates an association between the TyG index and the risk of carotid plaques in Asia. Further studies are required to substantiate these findings.

Potassium channel-related genes (PCRGs) play an important role in hepatocellular carcinoma (HCC) development, recurrence, and immunotherapy tolerance. We aimed to develop a new prognostic model associated with PCRGs that can be used for prognosis and immunotherapy prediction in HCC patients. The transcriptional profiles and clinical data related to HCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed PCRGs were identified using the "edgeR" package. Prognostic model associated with PCRGs were constructed using univariate analysis, least absolute shrinkage and selection operator (LASSO), and multivariate regression analysis. The prognostic value of the model was evaluated through Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves. Additionally, the tumor immune microenvironment was assessed using single sample gene set enrichment analysis (ssGSEA) and the CIBERSORT algorithm. Finally, potential drugs targeting signature genes were predicted. We successfully constructed a prognostic signature based on PCRGs, and the prognostic results were superior in the low-risk group. The nomogram demonstrated satisfactory predictive performance in estimating overall survival (OS) in HCC patients. The results of immune cell infiltration and predictions of immunotherapy response revealed that the low-risk group exhibited a more favorable response to immunotherapy. In addition, signature gene expression was significantly correlated with antitumor drug sensitivity. In conclusion, the characteristics of PCRGs serve as valuable tools for accurately assessing the prognosis and tumor microenvironment of HCC patients. Additionally, PCRGs markers can facilitate precision therapy in HCC management.

Congenital adrenal hyperplasia (CAH) is a rare disorder with autosomal recessive inheritance; it was historically known as adrenogenital syndrome. Patients with virilizing forms of CAH and a 46,XX karyotype present with varied degrees of hyperandrogenism due to different genetic defects in the adrenal steroidogenesis pathway. This comprehensive review describes a simplified diagnostic approach for patients with atypical genitalia and 46, XX DSD. It highlights the importance of a detailed history and clinical examination, with specific pointers toward the etiological diagnosis. There is a need for utilizing standardized liquid chromatography/tandem mass spectrometry (LC-MS/MS) assays to accurately diagnose these disorders of steroidogenesis. Choosing appropriate molecular testing methods has significant implications for establishing the diagnosis and providing genetic counseling.

Breast cancer (BC) threatens women's health, and the prognosis is dismal. Folic acid metabolism affects cancer prognosis, but research on folic acid metabolism-related genes (FMRs) in BC is scarce. We used TCGA-BRCA as the training set and GSE21653 as the validation set. Five FMRs (PLAT, SERPINA3, IFNG, SLC19A1, NFKB2) were screened via univariate and LASSO Cox regression analyses, and a prognostic model was built based on multivariate Cox regression analysis. The model showed excellent predictive performance. Differentially expressed genes in high- and low-risk groups were enriched in steroid hormone biosynthesis and neuroactive ligand-receptor interaction pathways. The low-risk group exhibited higher immune cell infiltration and better immunotherapy response. AM-5992 and 5-fluorodeoxyuridine 10mer may be potential BC drugs. This FMR-based model can accurately predict BC prognosis, offering a clinical reference.

Cushing's syndrome (CS) is associated with high morbidity and mortality triggered by increased risk for cardiovascular events. Nevertheless, no screening tool to predict the individual risk for these events in patients with Cushing's syndrome has been established. Nonenhanced electron-beam computed tomography scans with calculation of the Coronary Artery Calcium (CAC) score may offer a non-invasive method. Hence, we evaluated the diagnostic accuracy of Agatston score to predict the risk of a cardiac event in patients with Cushing's syndrome. Single center prospective study of 34 patients with endogenous CS Multidetector computer tomography and calculation of CAC score was performed at diagnosis of CS. Prevalence of cardiovascular events was documented with median follow-up over 5 years and results were compared with data from the Heinz Nixdorf Recall (HNR) Study. In addition, correlations of CAC score with parameters of cortisol excess were evaluated. CAC score was significantly higher in CS patients with a cardiovascular event than in patients without an event (117 vs. 90; p=<0.01). An odds ratio of 31.7 (p=0.03, 95% CI: 1.3-773.0) for a cardiovascular event could be shown in Cushing's syndrome patients with a CAC score>75th risk factor-specific reference percentile, while the odds ratio in the HNR study was 4.5 (p<0.01, 95% CI: 3.0-6.9). No correlation between the degree of cortisol excess and CAC score was evident. The CAC score>75th risk factor-specific reference percentile could offer a useful screening tool to precise the cardiovascular risk in patients with Cushing's syndrome.

The mitochondrial protein NAD(P)⁺ transhydrogenase (NNT) has been implicated in the metabolic derangements observed in obesity. Mice with the C57BL/6J genetic background bear a spontaneous mutation in the Nnt gene and are known to exhibit increased susceptibility to diet-induced metabolic disorders. Most of the studies on NNT in the context of diet-induced obesity have compared C57BL/6J mice with other mouse strains, where differences in genetic background can serve as confounding factors. Moreover, these studies have predominantly employed a high-fat diet (HFD) consisting of approximately 60% of calories from fat, which may not accurately mimic real-world fat-rich diets. In this study, we sought to examine the role of NNT in diet-induced hypothalamic inflammation and metabolic syndrome by using a congenic mice model lacking NNT, along with a HFD providing approximately 45% of calories from fat. Our findings indicate that mice lacking NNT were more protected from HFD-induced weight gain but presented a worse performance on glucose tolerance test, albeit not in insulin tolerance test. Interestingly, the brown adipose tissue of HFD-fed Nnt ^+/+ mice presented a greater mass and a higher whole-tissue ex-vivo oxygen consumption rate. Also, HFD increased the expression of the inflammatory markers Il1β, Tlr4 and Iba1 in the hypothalamus of Nnt ^-/- mice. In conclusion, our study highlights the importance of NNT in the context of diet-induced obesity and metabolic syndrome, indicating its contribution to mitigate hypothalamic inflammation and suggesting its role in the brown adipose tissue increased mass.

A proportion of patients with primary aldosteronism (PA) have a paradox increasein plasma-Aldosterone (P-Aldosterone) concentration (PAC) during the Captopril Challenge Test (CCT). This study aimed to investigate if a paradoxical rise in PAC during CCT, was associated with clinical characteristics or outcomes inpatients with PA. We hypothesized that a paradoxical response to CCT is ameasure of disease severity, reflected by a higher baseline aldosterone/renin-ratio (ARR). A retrospective study of patients with PA,confirmed by CCT, who were referred for adrenal venous sampling between May 2011and August 2021 were eligible. Patients with an increase in PAC>10% frombaseline during CCT were classified as cases, while patients with 10 to 30% suppression were classified as controls. Of 167 patients referred, 116 (70%) were eligible for this study. Based on the CCT, 61/116 (53%) were classified as cases while 55/116 (47%) were classified as controls. The baseline ARR was 122 pmol/mIU (IQR: 65 to 223) for cases and 137 pmol/mIU (IQR: 65 to 223) for controls (p=0.66). Cases had lower systolic blood pressure (p=0.02) and higherpotassium levels (p=0.05) compared to controls. Complete clinical remission was obtained in 22 of 31 (71%) of the cases and 13 of 27 (48%) of the controls (p=0.03) after adrenalectomy. In conclusion, a paradoxical response to CCT wasnot associated with ARR. By contrast, patients with a paradoxical response did have lower systolic blood pressure, higher potassium levels, and markedly higher odds of full clinical remission after adrenalectomy.

The relationship between serum homocysteine (Hcy) levels and atrial fibrillation (AF) recurrence following catheter ablation remains unclear. This meta-analysis aims to investigate this association. Comprehensive searches in PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases identified relevant studies published up to May 25, 2024. Cohort studies that measured pre-ablation serum Hcy levels and reported AF recurrence post-ablation were included. Data were analyzed using random-effects models by incorporating the potential influence of heterogeneity, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated for the association between serum Hcy levels and AF recurrence. Eleven retrospective cohort studies involving 2147 patients with AF who underwent catheter ablation were analyzed. Higher pre-ablation serum Hcy levels were associated with an increased risk of AF recurrence (OR for per 1 μmol/l increment of Hcy: 1.22, 95% CI: 1.17 to 1.28, p<0.001; I²=0%). Additionally, studies that categorized Hcy levels also found a higher risk of AF recurrence in patients with elevated Hcy (OR for patients with a high versus a low serum Hcy: 2.75, 95% CI: 2.02 to 3.75, p <0.001; I²=0%). Funnel plots and Egger's regression test indicated low risks of publication bias. In conclusions, elevated pre-ablation serum Hcy levels are significantly associated with an increased risk of AF recurrence post-catheter ablation. These findings suggest that Hcy could be a valuable biomarker for predicting AF recurrence and may inform pre-ablation risk stratification. Further prospective studies are warranted to confirm these results.

We aimed to characterize the clinical features and remission rates of patients with Cushing's Disease (CD) without magnetic resonance imaging (MRI) detectable pituitary adenoma compared to CD patients with MRI-detectable pituitary adenoma.All patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) without MRI-detectable pituitary adenoma underwent high-dose dexamethasone suppression test, corticotropin-releasing hormone stimulation test, and/or bilateral inferior petrosal sinus sampling (BIPSS). The diagnosis of CD in patients without MRI-detectable adenoma was confirmed when the results of dynamic testing and sampling concordantly indicated ACTH-producing adenoma.These patients were included in MRI-undetectable group. Patients with ACTH-dependent CS had pituitary adenoma≥6 mm and those with pituitary adenoma<6 mm but BIPSS findings indicative of CD were included in MRI-detectable adenoma group. The study included 60 patients without MRI-detectable adenoma and 74 patients with MRI-detectable adenoma. At presentation, patients without MRI-detectable adenoma were older [47 years (30.25-58) vs. 40.5 years (29-49), p=0.036]. Hypertension (65% vs. 47.3%), diabetes mellitus (58.3% vs. 39.2%), and cardiovascular disease (13.3% vs. 2.7%) were more common in patients without MRI-detectable adenoma (p=0.040, p=0.027, p=0.020; respectively). The transsphenoidal surgery as initial treatment was higher in the patients with MRI-detectable adenoma group (97.3% vs. 80%, p=0.001). Third-month remission (60.4% vs. 63.8%, p=0.700) after surgery, and remission rates in the last visit (65.3% vs. 79.7%, p=0.077) were similar between the two groups. Inconclusion, the absence of an MRI-detectable adenoma underscores the necessity for comprehensive management.