Hormone and Metabolic Research最新文献

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.

The diagnosis of adrenal insufficiency (AI) is challenging due to nonspecific symptoms. Measuring 8 AM serum cortisol levels is a common screening test, but its accuracy in predicting AI remains uncertain. This study aimed to evaluate the predictive diagnostic value of basal morning cortisol levels in suspected AI cases and compare them with levels in healthy individuals. We have conducted a retrospective multicentric cohort study. The study included an epidemiological cohort (patients with AI suspicion) and a control cohort (healthy volunteers). In the epidemiological cohort an ACTH-stimulation test was performed to confirm (AI group) or exclude (non-AI group) the disease. We have included 273 individuals (168 suspected AI cases and 105 controls). Basal cortisol levels were higher in the control group compared to the AI-suspected group (9.9±3.2 μg/dl vs. 7.7±3.3 μg/dl, p<0.001), though both were below the 15 μg/dl recommended threshold for excluding AI. Within the epidemiological cohort, even after a propensity score matching, taking into consideration sex, age and AI symptoms complaints, no significant difference in basal cortisol levels was found between patients with and without AI [6.10 (4.43; 8.45) vs. 7.14 (4.68; 12.15), p=0.128]. Logistic regression and ROC curve analyses showed a low predictive value for basal cortisol, with a positive predictive value of 18.9% and low specificity. AI patients more frequently experienced hypotension and nausea, compared with non-AI patients. Morning cortisol levels alone are unreliable for diagnosing AI. Revising cortisol cutoffs and incorporating symptom-based criteria may improve diagnostic accuracy.

We conducted this meta-analysis of randomized controlled trials (RCTs) with the aim of assessing the effect of 17β-estradiol plus norethisterone acetate on estradiol, testosterone, IGF-1, and SHBG in postmenopausal women. To our knowledge, this is the first meta-analysis of RCTs to assess these effects. Databases including the Web of Science, PubMed/Medline, Scopus, and EMBASE were searched to identify publications up to July 2024. The results were reported as weighted mean difference (WMD) and 95% confidence intervals (CI) generated by using a random-effects model according to the Der-Simonian-Laird model. Fifteen publications were included in current meta-analysis. Overall results from the random-effects model manifested a significant increase in estradiol (WMD: 55.30 pg/ml, 95% CI: 39.32, 7128, p<0.001) and SHBG (WMD: 18.48 nmol/l, 95% CI: 3.64, 33.33, p=0.015) levels, a significant decrease in FSH (WMD: -41.55 IU/l, 95% CI: -53.17, -29.92, p<0.001) and testosterone (WMD: -4.29 ng/dl, 95% CI: -5.38, -3.21, p=0.000) levels, and a non-significant decrease in IGF-1 levels (WMD: -9.70 μg/l, 95% CI: -34.21, 14.80, p=0.438) after treatment with 17β-estradiol plus norethisterone acetate on postmenopausal women. In conclusion, 17β-estradiol plus norethisterone acetate in postmenopausal women increases estradiol and SHBG concentrations and decreases FSH and testosterone concentrations, with no statistically significant effect on IGF-1.

The relationship between serum circCSPP1, circNIPSNAP3A, or circRFX8 and the occurrence and severity of non-alcoholic fatty liver disease (NAFLD) has yet to be fully elucidated. A total of 494 participants were divided into NAFLD and control groups, and clinical data, including demographic, physiological and biochemical parameters, were collected. Serum levels of circCSPP1, circNIPSNAP3A, and circRFX8 were measured using quantitative real-time PCR, and the severity of NAFLD was assessed by ultrasonography and quantitative computed tomography. The NAFLD group exhibited significantly higher levels of serum circCSPP1 compared to the control group (p=0.04). CircCSPP1 is significantly and independently associated with NAFLD. Participants with high serum circCSPP1 levels (>66th percentile) had a greater prevalence of mild and advanced NAFLD, as well as higher triglyceride levels, compared to those with low circCSPP1 levels (<33rd percentile) (p<0.05 for all). No significant correlations were observed between circNIPSNAP3A or circRFX8 and the occurrence or severity of NAFLD. These findings suggest that serum circCSPP1 is associated with the occurrence and severity of NAFLD, potentially mediated by hypertriglyceridemia.

Heightened aldosterone levels are associated with increased risk of renal sequelae, cardiovascular morbidity and mortality. Historically, primary aldosteronism is linked to hypertension. However, growing evidence reveals its presence even in normotensive individuals. This review consolidates data from diverse sources, delves into clinical studies of this underexplored condition, discusses the potential mechanisms, and provides a comprehensive and an up-to-date overview of the current state of knowledge. It highlights the evidence and understanding of normotensive primary aldosteronism, summarizes findings, and identifies opportunities for future research in this area. By addressing the clinical evidence, risk of hypertension development and possible mechanisms involved, this review aims to advance the understanding of this distinct form of primary aldosteronism and inspire further research in this emerging field.

Blood urea nitrogen (BUN) is a key metric when evaluating the renal function of a given patient. Individuals with chronic kidney disease also often present with abnormal thyroid functionality. The specific association between BUN and thyroid function, however, is not well understood. This study was thus developed to explore how BUN levels within the normal range are related to thyroid activity among adults in the USA. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged for these analyses. Linear regression and smoothed curve fitting approaches were employed to examine the association between BUN levels and measures of thyroid function, with appropriate weighted and subgroup analyses. The 2007-2012 NHANEs cycles included 6231 eligible adults with BUN levels from 2.5-8.0 mmol/l. Under adjusted models, a higher BUN level was associated with reductions in FT3 (β=-0.01; p=0.047), TT3 (β=-1.08; p=0.003), and TT4 (β=-0.10; p=0.003) levels. In subgroup analyses, BUN levels were respectively found to be negatively correlated with FT3 and TT4 levels in subjects who were inactive and active. These findings are consistent with reduced FT3, TT4, and TT4 levels being correlated with higher BUN levels within the normal range among American adults. In non-physically active subjects, FT3 levels were more closely related to increasing BUN levels, whereas TT4 levels were more closely related to BUN levels among physically active subjects. However, additional research will be vital to clarify the mechanisms that underlie these results.