Hormone and Metabolic Research最新文献

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.

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 taking their replacement therapy at some point. More than 50% of patients reported 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 is currently not evidence-based but opinion-driven. Our findings highlight the need for further investigations of shift workers with AI.

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.

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.

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.

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.