Hormones-International Journal of Endocrinology and Metabolism最新文献

Introduction: Heart failure (HF), a leading cause of morbidity and mortality, is characterized by a complex pathophysiology involving neurohormonal activation, metabolic dysregulation, and multiple hormonal deficiency syndrome (MHDS). MHDS is common in HF, affecting up to 90% of patients, and is associated with worse outcomes. This systematic review aims to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in the management of HF.

Methods: We conducted a comprehensive search of PubMed, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) examining TRT in HF patients up to September 15, 2024. Studies were included if they involved human subjects aged 18 or older with a confirmed diagnosis of HF and had a follow-up period of at least 4 weeks. We excluded reviews, animal studies, observational studies, and trials without randomization.

Results: Our search yielded 653 records, of which 12 studies met the inclusion criteria. Key findings include significant improvements in muscle strength and aerobic capacity as well as increases in lean muscle mass and decreases in fat mass in certain trials. Additionally, improvements in insulin sensitivity and shortening of the QT interval were reported. TRT did not consistently affect blood pressure, lipid profiles, or heart rate, nor did it lead to any serious adverse effects.

Discussion: While TRT has demonstrated potential benefits in HF patients, particularly in improving physical function and metabolic profiles, the current evidence is limited by small sample sizes and short follow-up periods. Larger event-driven RCTs evaluating hard endpoints are needed to determine whether TRT should be integrated into standard HF therapies.

Purpose: Generalized glucocorticoid resistance (GGCR) is caused by variants in the NR3C1 gene, which encodes the human glucocorticoid receptor (hGR). To date, 39 pathogenic variants of NR3C1 have been reported, primarily in the ligand-binding domain (LBD). This study presents a novel case of the NR3C1 variant located in the N-terminal domain (NTD) of hGR, highlighting its clinical and molecular significance in glucocorticoid resistance.

Case presentation: The patient was a 21-year-old woman presenting with chronic fatigue, irregular menstrual cycles, and osteopenia, though without any clinical signs of Cushing's syndrome. She underwent a standard evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. Endocrinological tests revealed elevated levels of ACTH, morning serum cortisol, aldosterone, DHEAS, 11-deoxycortisol, pregnenolone, and corticosterone, as well as increased urinary-free cortisol excretion. The low-dose dexamethasone suppression test (LDDST) showed suppression of cortisol levels. Molecular analysis via Whole Exome Sequencing (WES) identified a novel heterozygous pathogenic variant, c.220 C > T (p.Gln74Ter), in the NR3C1 gene. This confirmed the diagnosis of glucocorticoid resistance syndrome.

Conclusion: This case contributes to expanding the mutational spectrum of NR3C1 in glucocorticoid resistance syndrome, supporting more accurate diagnosis and genetic counseling for affected individuals.

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can give rise to immune-related adverse events such as ICI-related diabetes mellitus (DM).

Case presentation: We herein present the case of a 59-year-old Japanese man with malignant melanoma who developed ICI-related DM after 18 months of nivolumab treatment. He experienced marked hyperglycemia and diabetic ketoacidosis without a personal or family history of diabetes. Laboratory findings revealed initial preservation of insulin secretion but a rapid decline in C-peptide levels in the absence of islet autoantibodies. He was therefore diagnosed with ICI-related DM. This case fulfilled the criteria for fulminant type 1 DM but lacked the typical human leukocyte antigen alleles associated with conventional type 1 diabetes. No metastasis or morphological changes were apparent on CT scans of the pancreas, and magnetic resonance cholangiopancreatography did not show dilation or interruption of the main pancreatic duct. However, diffusion-weighted magnetic resonance imaging revealed high signal intensity with low apparent diffusion coefficient values in the pancreas, likely indicative of fibrosis or infiltration of inflammatory cells.

Discussion: This case underscores that ICI-related DM should be considered a potential immune-related adverse event as well as pointing to the benefit of diffusion-weighted imaging for assessment of pancreatic involvement at an early stage of the disease.

Purpose: The causal relationship between hyperthyroidism and knee osteoarthritis (KOA) remains to date unknown. We aimed to examine the potential causal relationship between hyperthyroidism status and the risk of developing KOA via a bidirectional two-sample Mendelian randomization (MR) approach.

Methods: Single-nucleotide polymorphism (SNP) data related to hyperthyroidism and KOA were obtained from a genome-wide association study (GWAS) in Europe. KOA was used as the outcome variable and hyperthyroidism was used as the exposure factor. The inverse-variance weighted (IVW) method served as the primary analytic tool and heterogeneity and pleiotropy were evaluated via sensitivity analysis.

Results: The IVW method indicated that hyperthyroidism status has a causative influence on the risk of developing KOA [OR, 1.046; 95% confidence interval (CI), 1.013-1.080; P = 0.006]. No significant reverse causality was detected. Sensitivity analyses validated the robustness of these findings.

Conclusions: Hyperthyroidism status can causally increase the risk of developing KOA. This result indicated that the risk of developing KOA may be decreased by controlling hyperthyroidism.

Purpose: Hereditary disorders of vitamin D metabolism are rare diseases. This review summarizes the current knowledge in this field and highlights the complicated metabolism of vitamin D.

Methods: PubMed and Google Scholar databases were searched in English. The keywords rickets, VDDR, vitamin D, metabolism, hypercalcemia, CYP2R1, CYP3A4, CYP24A1, and receptor were used and original and review articles were retrieved.

Results: Vitamin D is produced in the skin following the action of ultraviolet light on 7-dehydrocholesterol or is taken up by food. The active form of the hormone 1,25(OH)₂D is produced after two-step hydroxylations. The first hydroxylation takes place in the liver, in which 25(OH)D is produced by the enzyme CYP2R1. The second hydroxylation occurs in the kidneys where 1,25(OH)₂D is produced by CYP27B1. Mutations in the genes encoding these enzymes can lead to vitamin D-dependent rickets type 1B (VDDR1B) and VDDR1A, respectively. CYP24A1 is the main catabolic enzyme of vitamin D. Loss-of-function mutations of the CYP24A1 gene can lead to idiopathic infantile hypercalcemia (IIH). Moreover, loss-of-function mutations of the vitamin D receptor (VDR) gene can cause VDDR2. Recently, gain-of-function mutations of the CYP3A4 gene have been found to be responsible for a distinct form of rickets, VDDR 3, characterized by accelerated clearance of 1,25(OH)₂D.

Conclusions: Based on the evidence in the current literature, this article thoroughly reviews the metabolism of vitamin D, clinical symptoms, imaging findings, and available treatments for the different types of hereditary disorders related to vitamin D metabolism and action.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of end-stage liver disease and liver transplantation in the Western world, with an approximate prevalence of 30% worldwide which is continuously rising. It is characterized by intrahepatic fat deposition along with at least one cardiometabolic risk factor, such as diabetes mellitus, obesity, hypertriglyceridemia, and hypertension. MASLD consists of a spectrum of liver diseases ranging from simple liver steatosis to steatohepatitis, liver fibrosis, and cirrhosis. Recently, the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD), and the European Association for the Study of Obesity (EASO) released the latest guidelines regarding the management of patients with MASLD. This article highlights the critical points of these guidelines and emphasizes problematic issues that need further evaluation.

Background: Diabetes, a chronic metabolic disorder characterized by ineffective blood sugar regulation, affects millions of people worldwide, with its prevalence projected to more than double in the next 30 years. Diabetes-related complications are severe and sometimes life-threatening, including cardiovascular disease, kidney failure, and blindness, this posing a significant challenge, especially in low- and middle-income countries. This study explored the integration of artificial intelligence (AI) into diabetes management, emphasizing its transformative potential in healthcare.

Objectives: To evaluate the role of AI in enhancing diabetes management and to identify the challenges and opportunities associated with its implementation.

Methods: A systematic review following the PRISMA guidelines was conducted by analyzing the literature published from January 2020 to May 2024. This review focused on the application of AI in diabetes diagnosis, personalization of treatment, and predictive analytics.

Results: The ability of AI to analyze large datasets and identify complex patterns shows promise in improving diabetes management. AI-assisted diagnostic tools enhance diagnostic accuracy, enable early detection, and support personalized treatment plans, thereby reducing human error. AI has also facilitated research breakthroughs in genomics and drug discovery. Furthermore, AI-powered predictive analytics enhances clinical decision-making and supports precision medicine. Despite these advancements, challenges remain in such issues as data quality, technical infrastructure, and ethical considerations, emphasizing the need for responsible AI development that focuses on patient privacy and transparency.

Conclusions: AI has significant potential to revolutionize diabetes management and healthcare delivery. Combining AI's analytical processes with clinical expertise can substantially improve the quality of care. Addressing data, technology, and ethical challenges is crucial for fully harnessing AI's potential, thereby enhancing patient well-being and healthcare outcomes.

Objectives: To investigate medication non-adherence and its determinants in diabetes, hypertension, and hyperlipidemia.

Methods: In a multicenter, cross-sectional, non-interventional study, 518 diabetic, 721 hypertensive, and 463 hyperlipidemic patients were recruited, using consecutive sampling, in Greece during the COVID-19 pandemic. Medication adherence was measured with the Adherence to Refills and Medications Scale (ARMS). Multiple linear regressions with robust standard errors investigated the predictors of the ARMS summary score.

Results: Perfect adherence was estimated at 16%, 12%, and 11%, and low adherence at 38.8%, 61.3%, and 66.7% in diabetes, hypertension, and hyperlipidemia, respectively. The factors that significantly increased the likelihood of non-adherence were the following: (a) lower age, female gender, no public health insurance, high perceived threat of illness, low satisfaction with physician consultations, shorter consultations, bad general health, fewer comorbidities, and type 2 diabetes; (b) male gender, not being married, low education, no public insurance, smoking, frequent drinking, shorter consultations, self-perceived inadequacy of knowledge, negative views of medication, presence of comorbidities, fewer medicines being used, and high blood pressure in hypertension; and (c) lower age, not being employed, smoking, frequent drinking, no public insurance, low satisfaction with consultations, negative views of medication, taking 3-4 medicines, high LDL, and low HDL and triglyceride levels in hyperlipidemia. Different curvilinear associations of adherence with BMI and exercise were also found.

Conclusion: Medication non-adherence is very common in diabetes, hypertension, and hyperlipidemia. Strategies to improve adherence should consider the different determinants of non-adherence among patient groups.

Purpose: Cyathula prostrata (C. prostrata) a medicinal plant from tropical Africa, is traditionally used in Western Cameroon to treat female infertility. This study investigated the hormone-like effects of the aqueous extract of C. prostrata (AECp) leaves and stems on the onset of puberty and various reproductive parameters in immature female Wistar rats.

Methods: Five groups of immature female rats received daily oral doses of AECp for 20 consecutive days. Post-treatment body, ovarian, and uterine weights were recorded, along with uterine and ovarian protein levels, ovarian cholesterol levels, and blood hormone concentrations (FSH, LH, estradiol, and progesterone).

Results: AECp increased the growth rate in all treated animals. It reduced the age at vaginal opening by 2 to 6 days compared to controls. Secondary and tertiary follicles increased by 32.7% and 37.7%, respectively, in AECp-treated rats (96 mg/kg and 64 mg/kg). AECp significantly reduced uterine and ovarian protein levels by 21.3% and 27.8% at 64 mg/kg dosage. Regardless of dose, AECp lowered ovarian cholesterol and serum FSH levels (p < 0.001). Serum progesterone, estradiol, and LH levels increased significantly at 64 mg/kg compared to controls.

Conclusion: This study demonstrates AECp's positive effects on the onset of puberty and ovarian folliculogenesis in immature female rats.