Journal of Endocrinological Investigation最新文献

Purpose: Patients with adamantinomatous craniopharyngiomas (aCP) often present hypothalamic involvement (HI) either by the tumor or therapeutic interventions, resulting in hypothalamic obesity (HyOb). This study aims to investigate how appetite sensations and orexigenic and anorexigenic hormones response may contribute to the HyOb pathogenesis in these subjects.

Subjects and methods: Fifteen patients with aCP submitted to surgical resection (31,1 ± 12 years; 9 women) and 15 controls (31 ± 11,7 years) paired by sex, age and BMI were included in this cross-sectional study. Leptin and adiponectin were measured in basal conditions (T0'). Glucose, insulin, ghrelin, GLP-1, and PYY levels were assessed at T0', T30', T60', T120', and T180' minutes after a standard meal test. Sensations of hunger, fullness and prospective food consumption were measured using a visual analogic scale at the same time points.

Results: Intergroup differences on appetite sensations and biochemical variables were not significant between patients with aCP and controls. Intragroup analyses revealed distinct post-meal dynamics: compared to matching controls, patients with aCP showed earlier increase in hunger, and decrease in fullness (both P = 0.005) and prospective food consumption (P = 0.06) ratings from T0' to T180'. There was a tendency towards higher fasting leptin concentrations (P = 0.06), while adiponectinemia was significantly lower (P = 0.002). Insulin and HOMA-IR (both P < 0.01) were higher at T180', whereas the anorexigenic hormones GLP-1 (P = 0.03) and PYY (P = 0.02) were higher at T120'. PYY and ghrelin showed earlier postprandial rise and fall, respectively, in patients with aCP.

Conclusions: Although intergroup differences were limited, our intragroup analyses revealed reduced satiety persistence and earlier appetite rebound, particularly in patients with HyOb and severe HI, providing new insights into the complex, multifactorial pathophysiology of HyOb associated with aCP.

Purpose: To evaluate the efficacy and safety of osilodrostat in patients with Ectopic Cushing syndrome (ECS).

Methods: A retrospective, multicenter, real-world study of patients with ECS treated with osilodrostat. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal [ULN] or adrenal insufficiency development).

Results: A total of 17 patients with ECS were identified. Most of the cases (88.2%, n = 15) were classified as severe Cushing´s syndrome (UFC > 5 ULN). Two patients received osilodrostat as first-line therapy, 9 as second line and 6 as a third line. Fourteen patients were treated with osilodrostat in monotherapy and 3 in combination with other treatments. The initial doses of osilodrostat ranged between 4 and 30 mg/day and the maximum doses between 4 and 60 mg/day. Response to osilodrostat was evaluated in 16 patients because one patient died few days (< 30) after the initiation of the treatment. We found that 88% (n = 14/16) were complete responders while 2 patients had partial response (UFC reduction > 50% but with no normalization). The median time to achieve hypercortisolism control was 4.5 weeks (range 1–12), and 40% of the cases had normal UFC after 1 month of treatment. Six patients developed adverse events associated with the use of osilodrostat: 3 had adrenal insufficiency, 1 QT prolongation and 1 deterioration of blood pressure control.

Conclusion: Overall, osilodrostat controls hypercortisolism in approximately 90% of the patients with ECS and severe hypercortisolism and with normalization of UFC in 40% of cases after just 4 weeks of treatment. Therefore, osilodrostat should be considered as first-line treatment in patients with ECS, especially in patients with severe hypercortisolism.

Background: Cancer survivors have been considered individuals who have completed anti-tumor treatment and are in "remission". However, the definition is increasingly seen as insufficient due to a significant number of patients living with chronic or stable disease, as a result of advanced therapies, and according to a recent definition, "survivors" are all people living with and beyond cancer. Breast, prostate, lung and colorectal cancers are the most frequent tumors diagnosed in Europe with an increasing population of survivors. The longer life expectancy has made it necessary to assess the health status, comorbidities, and complications in cancer patients, mainly in the age range of 20-50 years. In particular, the long-lasting hormonal therapies in hormone-sensitive tumors and the immunotherapies, that are changing the cancer clinical scenario, have opened a broad landscape of late endocrine/metabolic toxicities.

Purpose: The aim of the present manuscript is to evaluate the late endocrine-metabolic complications in survivors of young adult or adult-onset cancers in the most prevalent tumors, analyzing risk factors for endocrine/metabolic disease, attempting to provide a indications for long-term surveillance and treatment strategies.

Conclusions: This paper highlights the importance of recognizing endocrine and metabolic complications, as well as identifying key risk factors that can suggest a more effective surveillance and management.

Introduction: Unilateral adrenalectomy is a definitive treatment for patients with primary aldosteronism (PA), yet its long-term renal and metabolic consequences remain insufficiently characterized. This study aimed to evaluate the incidence, risk, and cumulative burden of chronic kidney disease (CKD)/renal impairment, hyperuricemia, and gout in patients undergoing adrenalectomy compared to matched controls.

Methods: We used the Longitudinal Generation Tracking Database (LGTD) from the Health and Welfare Data Science Center, Taiwan, which includes data from 2 million individuals insured since 2000. We identified 1,110 primary aldosteronism (PA) patients diagnosed between 2000 and 2019, excluding those with adrenal insufficiency or pre-existing hyperuricemia, gout, CKD, or plasma cell dyscrasia. The final cohort included 537 PA patients who underwent unilateral adrenalectomy, with a control group matched 4:1 using propensity scores based on age, gender, and comorbidities. Outcomes included new-onset CKD/renal impairment, hyperuricemia, and gout. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models, and cumulative incidence was visualized via Kaplan-Meier plots.

Results: A total of 537 adrenalectomized PA patients and 2148 matched controls were analyzed. Compared with controls, the adrenalectomy group exhibited a significantly increased risk of CKD/renal impairment (aHR 2.07; 95% CI, 1.58-2.72; p < 0.0001) and gout (aHR 1.54; 95% CI, 1.02-2.32; p = 0.048), while the elevated risk of hyperuricemia did not reach statistical significance (aHR 1.92; 95% CI, 0.82-4.52; p = 0.424). Kaplan-Meier curves demonstrated a higher cumulative incidence of CKD and gout over a 20-year period in the adrenalectomy group, whereas the divergence in hyperuricemia incidence was less pronounced. Stratified analyses revealed age- and sex-specific risk variations, and antihypertensive medication adjustment post-adrenalectomy was associated with differential risk. Among adrenalectomized patients, metabolic comorbidities and aging were key predictors of adverse outcomes.

Conclusion: Patients with PA who undergo unilateral adrenalectomy are at increased long-term risk of CKD and gout. These findings underscore the need for vigilant renal and metabolic monitoring postoperatively, particularly in older patients and those with predisposing comorbidities.

Background: Pasireotide long-acting release (PasiLAR), a somatostatin multireceptor ligand, is effective in achieving biochemical control but can increase the risk of hyperglycemia in acromegaly. However, the impact of PasiLAR on lipid and glucose metabolism in patients with acromegaly has not been systematically studied. This systematic review aimed at synthesizing evidence on PasiLAR effects (as monotherapy or combination therapy with pegvisomant) on lipid and glucose metabolism in patients with acromegaly.

Methods: MEDLINE, Embase, Cochrane Library, and Web of Science were searched for studies published between 2000 and 2024. Prospective and retrospective studies reporting metabolic outcomes before and under PasiLAR treatment for a minimum follow-up of 6 months. Two reviewers screened eligible publications (3441), extracted outcomes, and assessed risk of bias.

Results: Nineteen studies (896 patients) were included in the meta-analysis. PasiLAR was associated with increased fasting plasma glucose (FPG) (mean difference [MD] 23.4 mg/dL, 95% confidence interval [95%CI] 18.8-28.1]) and glycated hemoglobin (HbA_1c) (MD 0.5%, 95%CI 0.4-0.7). A higher frequency of diabetes mellitus (DM) was observed after treatment (odds ratio 3.7, 95%CI 2.9-4.7). No significant changes in triglycerides, total cholesterol, or low-density lipoprotein cholesterol (LDL-C), and a modest but significant increase in high-density lipoprotein cholesterol (HDL-C) were recorded (MD 6.2 mg/dL, 95%CI 1.4-10.9]).

Conclusions: In this large meta-analysis, PasiLAR was associated with increased HDL-C, FPG, HbA1c, and frequency of DM in patients with acromegaly. There was no effect on triglycerides, total cholesterol, and LDL-C.

Prospero registration number: CRD42024544686.

Objective: Obesity is a biologically complex and heterogeneous disease that requires individualized, phenotype- and complication-oriented therapeutic strategies. The introduction of advanced pharmacotherapies, including GLP-1 receptor agonists (GLP-1 RA), dual Glucose-dependent Insulinotropic Polypeptide/Glucagon-like Peptide-1 (GIP/GLP-1) agonists, and emerging triple agonists, has facilitated a shift from weight-centric goals to precision-based obesity care. This review provides a clinical framework for pharmacologic treatment, organized by phenotype, obesity-related complications, age, and behavioral traits.

Design: Narrative review of randomized trials, meta-analyses, real-world evidence, and international guidelines through May 2025. Evidence was synthesized across key obesity phenotypes, cardiometabolic, hepatic, renal, mechanical, behavioral, and stratified by life stage, including pediatric, reproductive-age, and older adults, with attention to safety, cost-effectiveness, and special populations.

Results: In established Atherosclerotic Cardiovascular Disease, semaglutide significantly reduces major adverse cardiovascular events. Tirzepatide offers cardiometabolic benefits for high-risk people without overt disease. Both agents improve symptoms and function in Heart Failure with Preserved Ejection Fraction, irrespective of glycemia or weight loss. In Chronic Kidney Disease, they decrease albuminuria and eGFR decline. In Metabolic Dysfunction-Associated Steatotic Liver Disease, GLP-1 RAs and GIP/GLP-1 RAs demonstrate marked histological improvements. Mechanical complications such as osteoarthritis and sleep apnea are improved by anti-obesity medications-induced weight loss. GLP-1 RAs and naltrexone/bupropion prove effective against binge and emotional eating. In youths, liraglutide and semaglutide are both approved and effective. Liraglutide and orlistat preserve lean mass alongside resistance training and adequate protein intake in older and sarcopenic people.

Conclusions: An anti-obesity treatment framework focused on both phenotype and complication burden improves the personalization of obesity care and supports clinical decision-making throughout a person's lifespan.

Purpose: To analyse the effect on fasting glucose levels after one month of PTH 1-34 treatment in postmenopausal women with osteoporosis.

Methods: Twenty-six postmenopausal women treated with PTH 1-34 were enrolled. Patients with glucose ≥ 110 mg/dl and/or glycosylated hemoglobin > 48 mmol/mol were excluded. At baseline and after one month treatment, we measured fasting serum glucose, calcium, creatinine, PTH, 25(OH)vitamin D, OPG, RANKL, and BALP. Standardized questionnaires were administered to assess dietary caloric intake and physical activity.

Results: After one month, patients were divided according to the increase (group A) or decrease of glucose (group B). We found no difference between these two groups as regards anthropometric, biochemical evaluation, DXA measurements, dietary caloric intake, physical activity and fractures at baseline. There was no difference between groups in the number of patients treated before with bisphosphonates. Dietary caloric intake and physical activity after one month of therapy were not different in both groups. The mean delta glucose decrease after one month was 7%±4% in group B while the delta increase was 8%±5% in group A, p = 0.001. The only statistically significant difference between these groups, after one month, was an increase in mean delta BALP in group B compared to group A (group B:19 ± 23% vs. group A -0.7 ± 7, p = 0.04). Mean delta vitamin D and OPG increased, while mean delta PTH and RANKL decreased in both groups, without statistically significant differences between groups.

Conclusion: PTH 1-34 decreases mean serum glucose levels when bone formation is increased, as suggested by a significant increase in BALP in this group.

Purpose: The study aimed to estimate the prevalence of hypogonadism and erectile dysfunction (ED) in male living with the human immunodeficiency virus (HIV), MLWH, and to explore associations between HIV-related variables and gonadal/sexual function.

Methods: From 2019 to 2024, gonadal and sexual function were evaluated in consecutively enrolled MLWH through hormonal assessments and IIEF-15 questionnaire. Anthropometrics and HIV-related parameters, including type of Highly Active Anti-Retroviral Therapy, HAART, were also evaluated.

Results: Among 60 MLWH, 70.0% presented with ED. Hypogonadism was observed in 18.3%, primarily hypogonadotropic (72.7%). Although both eu- and hypogonadal MLWH presented pathological IIEF-15 scores, no differences in the five domains of IIEF-15 were found. Hypogonadal MLWH had significantly higher BMI (p = 0.046) and greater smoking prevalence (p = 0.002), and lower 17β-estradiol levels (p = 0.017). In the whole cohort, total testosterone was negatively correlated to BMI (r=-0.595, p = 0.001) and waist circumference (r=-0.656, p = 0.011), and positively to 17β-estradiol (r = 0.457, p = 0.006) and SHBG (r = 0.325, p = 0.033). Calculated free testosterone also negatively correlated with BMI (r=-0.519, p = 0.023) and WC (r=-0.719, p = 0.019). Considering HAART, ED was more prevalent among those using Integrase Strand Transfer Inhibitor (p = 0.017). Conversely, MLWH treated with Proteinase Inhibitors showed higher total testosterone, SHBG and 17β-estradiol levels (respectively, p = 0.018, p = 0.015 and p = 0.020), despite no differences in calculated free testosterone or prevalence of ED.

Conclusion: ED is highly prevalent multifactorial disorder in MLWH. Decreased serum testosterone levels, which are also related to increased visceral fat accumulation, are not the only driver of its onset. HIV-related factors, such as HAART, also appear to have an impact on gonadal and sexual function. A multidisciplinary approach, integrating infectious disease and sexual medicine expertise, is essential for optimal care.