Hormones-International Journal of Endocrinology and Metabolism最新文献

Aims: Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that can trigger the metabolic syndrome. Early prevention and treatment of NAFLD is still a huge challenge for patients and clinicians. The aim of this study was to develop and validate machine learning (ML)-based predictive models. The model with optimal performance would be developed as a set of simple arithmetic tools for predicting the risk of NAFLD individually.

Methods: Statistical analyses were performed in 2428 individuals extracted from the National Health and Nutrition Examination Survey (NHANES, cycle 2017-2020.3) database. Feature variables were selected by the least absolute shrinkage and selection operator (LASSO) regression. Seven ML algorithms, including logistic regression (LR), decision tree (DT), random forest (RF), extreme gradient boosting (XGB), K-nearest neighbor (KNN), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to construct models based on the feature variables and evaluate their performance. The model with the best performance was transformed into a diagnostic predictive nomogram (DPN). The DPN was developed into an online calculator and an Excel algorithm tool. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and subgroup analyses were used to compare and assess the predictive abilities of the DPN and six existing NAFLD predictive models, including the ZJU index, the hepatic steatosis index (HSI), the triglyceride-glucose index (TyG), the Framingham steatosis index (FSI), the fatty liver index (FLI), and the visceral adiposity index (VAI).

Results: Among the 2428 participants, the prevalence of NAFLD was 47.45%. LASSO regression identified eight variables from 39 variables, including body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), triglyceride (TG), diabetes, hypertension, uric acid (UA), and race. Among the models constructed by the seven algorithms mentioned above, the LR-based model performed the best, demonstrating outstanding performance in terms of area under the curve (AUC, 0.823), accuracy (0.754), precision (0.768), specificity (0.804), and positive predictive value (0.768). It was then transformed into the DPN, which was successfully developed as an online calculator and an Excel algorithm tool. The diagnostic accuracy (AUC 0.856, 95% confidence interval (CI) 0.839-0.874, and AUC 0.823, 95% CI 0.793-0.854, respectively) and net clinical benefit of DPN in the training and validation sets were superior to those of the ZJU, HSI, TyG, FSI, FLI, and VAI. The results were maintained in subgroup analyses.

Conclusions: The LR model based on ML was developed, exhibiting good performance. DPN can be used as an individualized tool for rapid detection of NAFLD.

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.

Background: Sulfonylureas constitute the standard therapy for patients with HNF1A-MODY (maturity-onset diabetes of the young) but are characterized by an increased risk of hypoglycemia. While SGLT2 inhibitors (SGLT2i) may potentially represent a useful therapeutic option, data from the literature are scant.

Case presentation: We report the case of a young woman affected by HNF1A-MODY who was successfully and safely treated with an SGLT2i in addition to sulfonylurea. After SGLT2i initiation, an improvement in the patient's glycemic control was observed and was maintained over time. No adverse effects were noted and, in particular, no increase in ketonemia or ketonuria occurred.

Conclusions: The use of SGLT2i under controlled circumstances may represent a useful therapeutic option in patients with HNF1A-MODY.

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.

The endocannabinoid system (ECS), regulating such processes as energy homeostasis, inflammation, and muscle function, centers around cannabinoid receptors, including CB1. These receptors are mainly located in the central nervous system and skeletal muscles. Hyperactivity of CB1 receptors is linked to metabolic disorders and chronic inflammation, highlighting their potential as therapeutic targets for muscle hypertrophy and metabolic health. This systematic review, registered with PROSPERO (CRD42023462735), follows PRISMA-P guidelines and uses the PICO framework. It evaluates the effects of CB1 receptor antagonism on muscle hypertrophy in animal models and cell lines. Interventions include pharmacological antagonists, genetic modifications, and exercise-induced antagonism. A comprehensive search of databases such as PubMed, EMBASE, CINAHL, and SPORTDiscus, supplemented by gray literature and reference lists, yielded 571 references. From these, ten studies were selected, involving 338 rodents, using CB1 antagonists like rimonabant and AM251. The findings suggest that CB1 receptor antagonism enhances insulin sensitivity and glucose tolerance, reduces body fat, and promotes muscle growth through pathways such as PI3K/Akt and mTOR, as well as by improving autophagy and mitochondrial function. This review proposes CB1 receptor antagonism as a promising approach for enhancing muscle hypertrophy and improving metabolic health, with potential applications in treating such conditions as obesity, type 2 diabetes, and sarcopenia. Future research should aim to standardize intervention protocols and explore integrated therapies to fully harness the benefits of CB1 modulation.

Giant parathyroid adenoma (GPA) is an extremely rare cause of primary hyperparathyroidism (PHPT) and may sometimes mimic parathyroid carcinoma (PC). Parathyroid carcinoma is also a very rare entity. Both preoperative and postoperative diagnosis of the two conditions remains a challenge. The purpose of this article is to present the diagnostic and therapeutic approach used for a 76-year-old female patient with a GPA measuring 5.4 × 2.3 cm, mimicking PC. The patient was referred to our clinic for the management of severe hypercalcemia revealed during the neurological evaluation of psychiatric and cognitive symptoms, confusion, weakness, and bone pain. PHPT was confirmed based on the patient's biochemical profile, which showed extremely high levels of serum calcium and parathyroid hormone (PTH). Wholebody computed tomography revealed a large nodule below the inferior pole of the right lobe of the thyroid gland and no further pathology in other organs. En bloc resection of the tumor with removal of the ipsilateral hemithyroid and other involved tissues was performed. Histopathological evaluation was diagnostic for a GPA. Post-surgery hungry bone syndrome (HBS) developed and was treated. However, the patient succumbed 3 weeks later due to septic shock. GPA is an exceptionally rare endocrine tumor that should be suspected along with PC in patients with significantly elevated levels of PTH and calcium, and/or palpable neck mass. In our case, diagnosis was based principally on histopathological examination together with clinical presentation, biochemical profile, and imaging studies. Resection of the tumor remains the treatment of choice.

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: Canada has experienced a ten-fold increase in referrals for gender-affirming care. Clinical guidelines emphasize the importance of a comprehensive and systematic approach to outcome measurement for gender-affirming hormonal care. However, research is lacking on the investigation of outcomes of Canadian gender-affirming hormonal treatments.

Methods: In total, five databases were searched, as follows: MEDLINE, Embase, PsycINFO, Scopus, and CINAHL on December 26, 2023. To meet inclusion criteria, each study needed to be an original article including patients identifying as transgender or gender diverse (TGD) who were receiving gender-affirming hormonal care in Canada. The Critical Appraisal Skills Programme (CASP) and Joanna Briggs Institute (JBI) tools were used to assess the methodological quality of the study. Descriptive frequencies were calculated for demographic information and a narrative synthesis was conducted to summarize outcomes organized for different treatments.

Results: A total of 3315 articles were identified, with 34 articles being included, representing 3990 patients. Physiologic parameters were reported in 62% of the studies and patient-reported outcomes (PROs) in 50%, although only 32% utilized standardized patient-reported outcome measures (PROMs). In studies reporting quantitative results, testosterone treatments showed 80% effectiveness in achieving desired physical changes, while several studies demonstrated that estrogen and antiandrogen treatments improved mental health in 85% of patients. The narrative synthesis of the results reveals positive outcomes and limited adverse effects of gender-affirming hormone therapy; however, it also underscores the need for standardized, consistent outcome measurement tools, particularly PROMs.

Conclusion: The present systematic review highlights the need for standardized outcome reporting in gender-affirming hormone therapy, underscoring the need for measurement of the patient's perspective through PROMs. Resolving these issues can improve evidence-based practices and support high-quality, patient-centered gender-affirming hormone care.

Michael Somogyi (Somogyi Mihály, 1883-1971) was a Hungarian biochemist who developed his scientific career in Europe and, primarily, the United States. He gave the name to the eponymous Somogyi effect or Somogyi hypothesis (in short, rebound hyperglycemia after insulin-induced hypoglycemia, particularly nocturnal), which was an axiom in the treatment of diabetes for decades. Although it is currently debated whether the Somogyi hypothesis is a real or relevant phenomenon in patients with diabetes, Somogyi's other significant career achievements are often overlooked. The aim of this historical note is to compile and highlight Michael Somogyi's scientific achievements. Michael Somogyi was a pioneer in the administration of insulin to patients with diabetes in the United States and in devising a method for insulin production. In addition, he highlighted the relevance of diet in patients with diabetes and was one of the first chemists to be integrated into clinical laboratories. There, Somogyi standardized long-lasting biological determinations, such as that of amylase, and he was one of the first scientists to combine basic research (from his training as a biochemist) with clinical research in close collaboration with physicians caring for patients, which is what we know today as translational research. Notably, the trajectory of his scientific career resembles the rebound effect of Somogyi's hypothesis: after reaching a low point of work activity well below his professional qualifications, his effort and tenacity led to the aforementioned achievements, and he became part of the history of hypoglycemia and diabetes.