Reviews in Endocrine & Metabolic Disorders最新文献

Neuroendocrine tumors (NET) are frequently associated with glycemic disorders, such as prediabetes or diabetes, which may result from either surgical or medical treatments or hormonal hypersecretion by the tumor itself. Moreover, pre-existing diabetes is a known risk factor for NET development, with metabolic control and antidiabetic therapies potentially influencing tumor progression. The complex interplay between diabetes and NET, which share several molecular pathways, has spurred interest in the anti-cancer effects of antidiabetic medications. This is particularly relevant as new antidiabetic drugs continue to emerge, including sodium-glucose cotransporter-2 (SGLT2) inhibitors and incretin-based therapies, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists and dual GIP/GLP- 1 R agonists. This review explores the impact of these novel pharmacological options on NET development and progression through a comprehensive analysis of pre-clinical and clinical studies, with the purpose to evaluate safety and feasibility of introducing these drugs in the treatment of NETs patients. We conducted a comprehensive search of online databases, including PubMed, ISI Web of Science, and Scopus, for studies assessing the therapeutic effects and potential mechanisms of action of incretins and SGLT2 inhibitors in patients with NET. These novel antidiabetic drugs exhibit promising anticancer properties, potentially inhibiting tumor cell proliferation and inducing apoptosis, though concerns about certain cancer risks remain. Based on current evidence, the benefits of incretin-based therapies outweigh any potential cancer risks, leading to the proposal of tailored management algorithms for diabetes in NET patients, factoring in the diabetes aetiology, comorbidities, and life expectancy.

The purpose of our study was to evaluate the efficacy and safety of partial adrenalectomy (PA) in the management of pheochromocytomas. A systematic review and metanalyses of all randomized controlled trials and observational studies (comparative and non-comparative studies), including case series with at least 5 cases, reporting efficacy and safety outcomes of PA in the treatment of bilateral and/or inherited pheochromocytomas was performed. A total of 33 articles were included in this systematic review, including 22 observational comparative and 11 single-arm studies. The pooled rates of biochemical and clinical cure after PA were 99.7% (95%CI: 98.7-100) and 99.8% (95%CI: 98.8-100), respectively. The pooled complication rate was 5.9% (95%CI: 0.8-10.9). Tumor recurrence and metastatic rates were 4% (95%CI: 0-1.6) and 0% (95%CI: 0.00-0.6), respectively. Steroid supplementation was required in 7.6% (95%CI: 2.8-12.5) of patients. No significant difference was detected in acute adrenal crisis (odds ratio [OR] 0.44, 95%CI: 0.16-1.22), biochemical (OR 0.42, 95%CI: 0.05-3.85) and clinical cure (OR 0.42, 95%CI: 0.05-3.85), complication (OR 1.59, 95%CI: 0.28-9.13) and metastatic rate (OR 1.56, 95%CI: 0.59-4.15) between the group of partial and total adrenalectomy. Nevertheless, recurrence rate (OR 2.55, 95%CI: 1.24-5.23) was higher with PA, while the need for supplementation rate (OR 0.01, 95%CI: 0.00-0.01) was significantly lower than in the total adrenalectomy group. The conclusion of the study is that the probability of biochemical cure and the rate of complications is similar between the group of patients who underwent total and partial adrenalectomy, but PA is associated with a lower rate of adrenal insufficiency and a higher recurrence rate than total adrenalectomy.

Thyroid inflammation during pregnancy, particularly Hashimoto's thyroiditis (HT) and postpartum thyroiditis (PPT), has a strong genetic and epigenetic basis. Susceptibility to these conditions is associated with specific HLA haplotypes (HLA-DR3, DR4, DR5) and immune-regulatory genes, including CTLA-4, PTPN22, FOXP3, as well as thyroid-specific genes such as TSHR, TG, and TPO. CTLA-4 polymorphism (CT60) is linked to increased thyroid autoantibody production, while PTPN22 R620W variant disrupts immune tolerance, exacerbating autoreactive lymphocyte activation.Epigenetic modifications play a crucial role in HT and PPT pathogenesis. Dysregulation of microRNAs (miRNAs), including miR-146a, miR-142, miR-301, and miR-155, affects immune pathways by modulating T-cell responses and inflammatory cytokine production. Aberrant DNA methylation in genes regulating immune function, such as FOXP3 and CTLA-4, contributes to altered immune tolerance and disease progression.Oxidative stress further modulates disease severity by inducing DNA damage and enhancing inflammatory responses, particularly in pregnancy. Reactive oxygen species (ROS) promote thyroid autoimmunity by affecting placental function and fetal neurodevelopment. Understanding the interplay between genetic susceptibility, epigenetic regulation, and oxidative stress is essential for developing personalized management strategies. This review highlights the molecular mechanisms underlying HT and PPT and the potential of epigenetic biomarkers for early diagnosis and targeted therapies.

Insulin icodec is a novel once-weekly basal insulin analog subcutaneous injection seeking approval by the United States Food and Drug Administration (FDA) for use in both type 1 and type 2 diabetes mellitus. The mission of this manuscript is to provide a thorough overview of insulin icodec's clinical trials that were involved in its approval as well as review its pharmacology, pharmacokinetics, adverse effects, drug interactions, dosage recommendations, and regulatory issues. This article includes a thorough review of insulin icodec's safety and efficacy in type 1 and type 2 diabetes mellitus including its pharmacokinetic and pharmacodynamic profile. A systematic search of the electronic database of PubMed from inception until December 2024 using MeSH keywords was completed. Keywords used were icodec, insulin, type 1 diabetes, and type 2 diabetes. Overall, 14 clinical trials were identified and reviewed. The majority of the trials reviewed showed decreases in A1C as primary endpoints and non-inferiority and superiority with insulin icodec versus the comparator. In select studies, mild hypoglycemia was more evident in subjects taking insulin icodec versus the comparator but no other concerns were identified. The reviewed literature showed similar and sometimes improved glycemic control when insulin icodec was compared to other long-acting insulins both in insulin-naive and previously insulin-treated patients. Hypoglycemia was similar or slightly increased with insulin icodec when compared to other long acting insulins. Overall, icodec is a useful, new formulation of basal insulin that allows for less injections, improved compliance, and potentially improved glycemic control providing a new tool to practitioners managing patients with diabetes who need to be on insulin.

Despite bioelectrical impedance analysis (BIA)-derived phase angle (PhA) being recognized as a global marker of health, reflecting both cellular integrity and fluid distribution, its biological determinants still need to be described in youth. This narrative review provides a comprehensive framework examining to what extent dielectric properties shaping PhA are influenced by qualitative and quantitative determinants at multiple levels of body composition in healthy and clinical pediatric populations. At the atomic-molecular level, water content, glycogen, lipids, and ionic concentrations are expected to influence PhA by affecting electrical conductivity and/or capacitance. While the increase in the absolute values of intracellular (ICW) and extracellular water (ECW) enhances electric conductivity, an increase in the relative portion of ECW is expected to reflect hydration imbalances with an impact on electrical pathways. At the cellular level, body cell mass is a key determinant of PhA, mainly due to the presence of skeletal muscle cells favoring conductive and capacitive properties. At the tissue level, skeletal muscle architecture and orientation strongly influence conductivity, while increases in skeletal muscle mass positively impact PhA by enhancing electric conductivity and capacitance. Beyond the theoretical insights presented in this review, careful interpretation of dielectric data remains crucial due to the lack of methodological standardization. Future research should prioritize validated reference methods, investigate longitudinal changes, integrate localized BIA, and explore additional BIA models to refine the interpretation of PhA.

Cardiovascular diseases (CVD) are major lethal diseases worldwide. Imbalance of gut microbiota (GM) homeostasis affects the development and progression of CVD. Exercise can remodel GM and improve GM disorders in CVD patients. By combing the research progress of GM-mediated exercise intervention for CVD, it was found that 1) Streptococcus, Lactococcus, Enterobacter, Klebsiella, and Turicibacter are pathogenic bacteria in CVD patients; 2) Response to exercise to modulate the microbiota of CVD includes increasing the abundance of beneficial bacteria such as Bifidobacteria, Lactobacillus, Bacteroides, Faecalobacteria, and Roseburia, decreasing the proportion of Streptococcus, Enterobacter, and other pathogenic bacteria, and regulating metabolite-producing bacteria such as Prevotella and Ruminococcus; 3) Exercise can improve the CVD process via GM, by remodeling physiological mechanisms such as vascular function, cardiac function, autonomic function and hemodynamics, and molecular mechanisms such as regulation of DNA methylation, histone modification, non-coding RNAs; 4) Most of the existing studies have focused on aerobic exercise. The specific mechanisms, individualized intervention programs and long-term effects of different types of exercise on GM in CVD patients need to be further explored.

Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes, with limited treatment options. This systematic review consolidates longitudinal studies on the development of DPN, identifying key predictors to inform clinical interventions for DPN prevention. PubMed, Embase, and Cochrane databases were searched for peer-reviewed studies on DPN published before March 2024. Longitudinal studies involving populations with diabetes and investigating sociodemographic, lifestyle, anthropometric, and clinical predictors of DPN were included. Studies with missing data or high risk of bias were excluded. Predictors of DPN were extracted from included studies and recorded in an Excel file. Weighted mean differences (continuous variables) and relative risks (dichotomous variables) were calculated to assess predictors' significance. Twenty-seven studies analyzing 21 predictors were included. The median sample size and follow-up time were 985 and 72 months respectively. Age, HbA1c, BMI, diabetes duration, and systolic blood pressure were strong positive predictors of incident DPN, highlighting the role of glycemic control, weight management, and blood pressure optimization in reducing DPN risk. Modest associations were found for fasting plasma glucose, smoking, height, weight, waist circumference, sex, use of antihyperlipidemia drugs, and retinopathy. A subgroup analysis demonstrated that these findings were relevant to both Type 1 and Type 2 diabetes. Despite the heterogeneity observed in DPN diagnostic criteria and measurements of predictors across studies, several potentially modifiable risk factors for DPN were identified. These findings can help healthcare providers identify high-risk individuals and implement appropriate preventive measures targeting these factors for reducing the risk of DPN development.

Growth Hormone-Releasing Hormone (GHRH) is a hypothalamic hormone that stimulates GH secretion by the anterior pituitary gland. Ectopic production of GHRH by neuroendocrine tumors (NETs) is a rare cause of acromegaly, with some clinical and biochemical features indistinguishable from pituitary adenoma origin. Some clues for this diagnosis include pituitary MRI harboring hyperplasia, increased serum GHRH and extra-pituitary tumor detected in whole body scans. The preferable treatment, when possible, should be surgical resection of the NET. In cases with residual tumor, somatostatin analogs could be used as an alternative for adjuvant therapy for both tumoral and biochemical control of IGF-1. Life-long follow-up is needed as some patients may develop persistent pituitary hyperplasia or GH-adenomas due to prolonged GHRH exposure, with elevated IGF-1 levels even without NET recurrence. In such scenarios, medical therapy should be provided for hyperplasia cases and transsphenoidal surgery to patients with pituitary adenoma. If available, genetic test for MEN1 mutations should always be performed.

Acromegaly is a rare condition, and often diagnosis is delayed by several years, for most patients. Acromegaly is characterized by short and long-term respiratory, cardiovascular and metabolic comorbidities, with possible impact on mortality. In the last two decades, life expectancy has progressively increased in part due to a reduction in biochemically active disease, multidisciplinary treatment approaches and a reduction in complications, and the availability of new drugs. Of note, a leading cause of mortality, cardiovascular comorbidity, has been replaced by cancer(s). As such, neoplasms more frequently observed (colon, thyroid, breast, prostate, and stomach) in patients with acromegaly are receiving increased attention. Chronic exposure to increased growth hormone serum levels may contribute to an increase in the occurrence and progression of cancers. Various efforts have been made to determine the pathogenetic mechanisms involved. However, there are no clear medical-related societal agreement(s) in relation to screening methods or timing regarding neoplasm(s) diagnosis in patients with acromegaly. Additionally, independent and dependent risk factor data in patients with acromegaly is lacking. International/national registries could help lay the groundwork to better study the impact of cancer(s) in patients with acromegaly and subsequently lead to and validate the most appropriate diagnostic and therapeutic path forward.

The existing evidence on pituitary function impairment in non-neuroendocrine pituitary tumors (non-PitNETs) is limited and scattered. We performed a systematic review using PubMed, Embase, Scopus, and Cochrane of all reported studies that evaluated pituitary function in craniopharyngiomas, meningiomas, germinomas, pituitary lymphomas, pituicytomas, granular cell tumors, spindle cell oncocytomas, and pituitary metastases over the past 35 years. A total of 5,614 patients from 114 studies were analyzed. The weighted mean age was 35.01 ± 2.7 years (95% CI: 34.9-35.1) and 47.5 ± 14.1% (95% CI: 47.1-47.8) were women. The overall weighted proportion of hypopituitarism was 49.1 ± 24.2% (95% CI: 48.4-49.7) and arginine vasopressin deficiency (AVD) was 18.43 ± 16.6% (95% CI: 17.9-18.9). According to tumor type, prevalence of hypopituitarism was 67.3 ± 8.1% (95% CI: 66.5-68.9) for germinomas, 61.4 ± 20.8% (95% CI: 58.8-64.1) for metastases, 58.7 ± 22.2% (95% CI: 46.2-71.3) for lymphomas, 54.4 ± 30.8% (95% CI: 45.6-63.3) for pituicytomas, 53.8 ± 12.3% (95% CI: 47.5-59.8) for oncocytomas, 49.1 ± 17.2% (95% CI: 48.6-49.6) for craniopharyngiomas, 29.7 ± 16.6% (95% CI: 22.4-36.9) for granular cell tumors, and 11.5 ± 9.1% (95% CI: 10.8-12.3) for meningiomas. When comparing the most prevalent non-PitNETs, the weighted prevalence of hypopituitarism was higher in metastases compared to craniopharyngiomas (χ2 = 696.8, df = 1), p < 0.0001. Similarly, the weighted prevalence of hypopituitarism in craniopharyngiomas was higher compared to meningiomas (χ2 = 16,278.13, df = 1), p < 0.0001. In conclusion, non-PitNETs result in hypopituitarism in approximately half of the cases and AVD in nearly one-fifth. Pituitary metastases and craniopharyngiomas demonstrate greater local aggressiveness and a higher likelihood of disrupting hypothalamic-pituitary function compared to meningiomas.