Hormones-International Journal of Endocrinology and Metabolism最新文献

Objective and design: Glucocorticoids (GCs) have been widely used in symptomatic patients for the treatment of COVID-19. The risk for adrenal insufficiency must be considered after GC withdrawal given that it is a life-threatening condition if left unrecognized and untreated. Our study aimed to diagnose adrenal insufficiency early on through a GC reduction schedule in patients with COVID-19 infection.

Patients and measurements: From November 2021 to May 2022, 233 patients were admitted to the Geriatric Division of the University Hospital of Padova with COVID-19 infection. A total of 122 patients were treated with dexamethasone, after which the GC tapering was performed according to a structured schedule. It consists of step-by-step GC tapering with prednisone, from 25 mg to 2.5 mg over 2 weeks. Morning serum sodium, potassium, and cortisol levels were assessed 3 days after the last dose of prednisone.

Results: At the end of GC withdrawal, no adrenal crisis or signs/symptoms of acute adrenal insufficiency were reported. Median serum cortisol, sodium, and potassium levels after GC discontinuation were, respectively, 427 nmol/L, 140 nmol/L, and 4 nmol/L (interquartile range 395-479, 138-142, and 3.7-4.3). A morning serum cortisol level below the selected threshold of 270 nmol/L was observed in two asymptomatic cases (respectively, 173 and 239 nmol/L, reference range 138-690 nmol/L). Mild hyponatremia (serum sodium 132 to 134 nmol/L, reference range 135-145 nmol/L) was detected in five patients, without being related to cortisol levels.

Conclusions: A structured schedule for the tapering of GC treatment used in patients with severe COVID-19 can reduce the risk of adrenal crisis and acute adrenal insufficiency.

The increasing prevalence of type 2 diabetes mellitus (T2DM) and its microvascular and macrovascular complications necessitate an optimal approach to prevention and management. Medical nutrition therapy serves as the cornerstone of diabetes care, reducing reliance on diabetic medications for glycemic control and mitigating cardiovascular risk. The broadening field of research in the effect of low glycemic index (GI) and/or glycemic load (GL) diets on individuals with T2DM has yielded promising results in the existing literature. Adopting low-GI and GL dietary patterns contributes to minimizing fluctuations in blood glucose levels, thus presenting a good strategy for achieving enhanced glycemic control. Furthermore, the above dietary practices may offer a viable alternative and practical approach to weight management in individuals with T2DM. However, clinical practice guidelines for diabetes dietary management show inconsistency regarding the certainty of evidence supporting the implementation of low-GI/GL nutritional patterns. This review aims to thoroughly evaluate the available data on the effectiveness of low-GI and low-GL diets in managing glycemic control and reducing cardiovascular risk factors.

Purpose: Evidence from previous experimental and observational research demonstrates that the gut microbiota is related to circulating adipokine concentrations. Nevertheless, the debate as to whether gut microbiome composition causally influences circulating adipokine concentrations remains unresolved. This study aimed to take an essential step in elucidating this issue.

Methods: We used two-sample Mendelian randomization (MR) to causally analyze genetic variation statistics for gut microbiota and four adipokines (including adiponectin, leptin, soluble leptin receptor [sOB-R], and plasminogen activator inhibitor-1 [PAI-1]) from large-scale genome-wide association studies (GWAS) datasets. A range of sensitivity analyses was also conducted to assess the stability and reliability of the results.

Results: The composite results of the MR and sensitivity analyses revealed 22 significant causal associations. In particular, there is a suggestive causality between the family Clostridiaceae1 (IVW: β = 0.063, P = 0.034), the genus Butyrivibrio (IVW: β = 0.029, P = 0.031), and the family Alcaligenaceae (IVW: β=-0.070, P = 0.014) and adiponectin. Stronger causal effects with leptin were found for the genus Enterorhabdus (IVW: β=-0.073, P = 0.038) and the genus Lachnospiraceae (NK4A136 group) (IVW: β=-0.076, P = 0.01). Eight candidate bacterial groups were found to be associated with sOB-R, with the phylum Firmicutes (IVW: β = 0.235, P = 0.03) and the order Clostridiales (IVW: β = 0.267, P = 0.028) being of more interest. In addition, the genus Roseburia (IVW: β = 0.953, P = 0.022) and the order Lactobacillales (IVW: β=-0.806, P = 0.042) were suggestive of an association with PAI-1.

Conclusion: This study reveals a causal relationship between the gut microbiota and circulating adipokines and may help to offer novel insights into the prevention of abnormal concentrations of circulating adipokines and obesity-related diseases.

Population aging is a global phenomenon driving research focus toward preventing and managing age-related disorders. Functional hypogonadism (FH) has been defined as the combination of low testosterone levels, typically serum total testosterone below 300-350 ng/dL, together with manifestations of hypogonadism, in the absence of an intrinsic pathology of the hypothalamic-pituitary-testicular (HPT) axis. It is usually seen in middle-aged or elderly males as a product of aging and multimorbidity. This age-related decline in testosterone levels has been associated with numerous adverse outcomes. Testosterone therapy (TTh) is the mainstay of treatment for organic hypogonadism with an identifiable intrinsic pathology of the HPT axis. Current guidelines generally make weak recommendations for TTh in patients with FH, mostly in the presence of sexual dysfunction. Concerns about long-term safety have historically limited TTh use in middle-aged and elderly males with FH. However, recent randomized controlled trials and meta-analyses have demonstrated safe long-term outcomes regarding prostatic and cardiovascular health, together with decreases in all-cause mortality and improvements in various domains, including sexual function, body composition, physical strength, bone density, and hematopoiesis. Furthermore, there are numerous insightful studies suggesting additional benefits of TTh, for instance in cardio-renal-metabolic conditions. Specifically, future trials should investigate the role of TTh in improving symptoms and prognosis in various clinical contexts, including sarcopenia, frailty, dyslipidemia, arterial hypertension, diabetes mellitus, fracture risk, heart failure, stable angina, chronic kidney disease, mood disorders, and cognitive dysfunction.

Theodoros Aretaios (1829-1893), having pursued advanced studies at home and abroad and possessing a wide range of competences and interests, was among the first Greek physicians to produce educational treatises for both students and doctors of medicine. Among these is his medical treatise Surgery which deals with thyroid operations and goiter symptoms as well as post-operative lesions which included a record of his extensive experience, learned recommendations, deep insights, and advanced techniques. In this medical archive, which is preserved in the National Library of Greece, there is, for example, the physician's vivid description of a thyroidectomy that he performed which illustrates his expertise as a surgeon as well as the surgical knowledge of his times. Aretaios was not the first to perform this operation in Greece: he was, however, the first to document it, which he did for the benefit of his fellow Greeks and of surgeons worldwide.

Purpose: To examine the determinants of health-related quality of life (HRQoL) of patients with type 2 diabetes (PwD) and multimorbidity (MM) (at least one co-occurring condition besides T2D) among sociodemographic, disease-related, and MM variables and the association of MM with therapeutic targets.

Methods: A total of 179 PwD attending primary care (PC) in Greece answered the 15 dimension HRQoL (15D) questionnaire between August 2019 and October 2020. Sociodemographic, disease-related, and MM characteristics were recorded. MM was categorized as concordant or discordant based on whether or not it was related to the pathophysiology of T2D. Independent predictors of the 15D score were examined in stepwise regression models among sociodemographic, disease-related, and MM variables and the association of MM with glycated hemoglobin (A1C) and low-density lipoprotein cholesterol (LDL-C) was assessed.

Results: The mean 15D score was 0.85 ± 0.11 and the mean MM count was 4.3 ± 1.8. Significant predictors of a higher 15D score were male gender, married state, higher monthly income, and more physical activity. Significant predictors of a lower 15D score were employment, depression, musculoskeletal disease, coronary artery disease, neuropathy, and MM count, but discordant had a stronger effect than concordant MM. Increasing MM count was not significantly correlated with A1C and was correlated with lower LDL-C.

Conclusion: Non-medical (physical activity and sociodemographic) rather than disease-related characteristics and discordant more than concordant co-occurring conditions affected HRQoL of multimorbid PwD who did not have worse (A1C) or achieved better (LDL-C) therapeutic targets. A generalist approach to the non-medical needs and overall health conditions of PwD could be promoted in PC within the social determinants of health and MM.

Silver-Russell syndrome 5 (SRS5) is characterized by asymmetric intrauterine growth restriction (IUGR), poor postnatal growth, macrocephaly at birth, and feeding difficulties. Other possible features include triangular shaped face, prominent forehead, hypertelorism, epicanthus, micrognathia, brachydactyly, clinodactyly of the 5th finger, and syndactyly of the 2nd and 3rd toes. Pathogenic variants of the HMGA2 (high mobility group AT-hook 2) gene, on chromosome 12q14, which regulates the transcription of growth factor IGF2, have recently been associated with this syndrome. Herein, we present a 2.5-year-old boy with growth delay, SRS-like phenotype, and a variant of uncertain significance in the HMGA2 gene, which has not, to the best of our knowledge, been described to date in the medical literature. So far, 28 pathogenic variants of the HMGA2 gene in patients with clinical SRS phenotype have recently been reported. Therefore, HMGA2 gene testing should always be done in SRS patients who are found to be negative for the typical 11p15 (epi)mutations and matUPD7, while the mutations should also be added to growth retardation disorder panels.

Purpose: Corticotropin-releasing hormone (CRH) plays an important role in relief of pain by releasing analgesia-associated molecules in several inflammatory states. During inflammation, peripheral CRH acts on cells of the immune system to stimulate the local expression of proopiomelanocortin (POMC) and the production of β-endorphin, which in turn binds to opioid receptors on sensory neurons to produce antinociception. In the present study, we further investigated the role of endogenous CRH in inflammatory pain by determining the effects of Crh-deficiency on this process.

Methods: For this purpose, we used Crh-deficient (Crh-/-) mice and their wildtype (Crh + / +) littermates in the CFA (Complete Freund's Adjuvant)-induced inflammatory pain model. Pain thresholds were evaluated with the Hargreaves apparatus.

Results: Our experiments showed that Crh deficiency led to increased pain response, which was associated with decreased POMC mRNA levels in locally inflamed paws of these mice. Furthermore, Crh-/- mice had higher paw edema than Crh + / + mice. Histological evaluation of inflamed paw tissues revealed increased inflammatory response in Crh-/- mice. Protein levels of proinflammatory cytokines, such as IL-6, TNF-α, and IL-1β, were higher in inflamed tissue of Crh-/- mice compared to wildtype mice. Corticosterone replacement increased the pain threshold of Crh-/- mice, restored their paw volume to the levels of wildtype mice, and significantly reduced their proinflammatory cytokine levels. Furthermore, glucocorticoid administration significantly increased POMC mRNA expression in the inflamed paw.

Conclusion: Our data suggest that genetic deficiency of CRH is associated with increased pain. This effect is likely attributable to the accompanying glucocorticoid insufficiency and is in part mediated by opioids expressed locally.

Background: The cardiometabolic index (CMI) is a new type of obesity index that is based on a combination of lipid levels and abdominal obesity indicators. It is closely correlated with the occurrence of diabetes mellitus, atherosclerosis, hypertension, and other diseases, thus playing an important role in the screening of metabolic diseases. This is coupled with hepatic steatosis and fibrosis which are characterized by excessive liver fat deposition. The aim of this study was to investigate the possible association between CMI and hepatic steatosis and liver fibrosis.

Methods: A cross-sectional investigation was conducted using the 2017-2020 National Health and Nutrition Examination Survey (NHANES) dataset to probe the relationship between CMI and hepatic steatosis and liver fibrosis, while multiple linear regression models were used to test the linear association between CMI and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Smooth-fit curves and threshold effects analysis were used to describe the nonlinear relationships. Subgroup analyses were performed according to gender, age, body mass index (BMI), hypertension, diabetes, cardiovascular disease, and smoking status.

Results: A total of 3084 adults aged 18-80 years were included in this analysis, and after controlling for a variety of variables, there was a significant positive correlation between CMI and CAP [20.38 (16.27,24.49)]. When subgroups were analyzed, this positive correlation was found to be stronger in the female population than in the male (P for interaction = 0.0303). Furthermore, the association between CMI and CAP was nonlinear. Using multiple regression analysis, it was shown that the linear relationship between CMI and liver fibrosis was not significant [-0.09 (-0.47,0.29)].

Conclusions: The findings suggest that elevated CMI levels are associated with hepatic steatosis, but that CMI is not linked to liver fibrosis. Larger prospective investigations are needed to confirm our findings.