Journal of Neuroendocrinology最新文献

{"title":"Changes in leptin and melanocortin peptides in cerebrospinal fluid after diet versus bariatric surgery","authors":"David M. Berger,&nbsp;Sunil K. Panigrahi,&nbsp;Jorge Arriaza Sagredo,&nbsp;Richard M. Smiley,&nbsp;Judith Korner,&nbsp;Sharon L. Wardlaw","doi":"10.1111/jne.70292","DOIUrl":"10.1111/jne.70292","url":null,"abstract":"<p>Peripheral metabolic signals elicit a host of neuronal responses that maintain energy balance and make it difficult to maintain diet-induced weight loss (WL). Why WL is sustained after bariatric surgery remains unclear but brain mechanisms have been implicated. The objective was to compare changes in leptin and the hypothalamic melanocortin system, consisting of proopiomelanocortin (POMC) and AgRP neurons, after WL from diet versus surgery to determine if diet-induced changes in melanocortin activity might be circumvented after surgery. Fourteen subjects (BMI 41.3) were studied before and 3.2-months after diet (WL 12.5%). Eighteen subjects (BMI 44.4) were studied before and 2.4-months after surgery (12-sleeve gastrectomy; 6-Roux-en-Y gastric bypass) (WL 15.0%); 11 were studied again 1-year after surgery (WL 29%). CSF measurements of POMC and POMC-derived ß-MSH were used as a surrogate of brain melanocortin activity. AgRP and leptin were measured in CSF and plasma. Leptin decreased in plasma and CSF at similar magnitudes after diet and surgery and there was a similar increase in the ratio of CSF/plasma leptin. Nonsignificant declines in CSF POMC but highly significant declines in CSF ß-MSH and ß-MSH/POMC ratio occurred after diet and surgery indicating a greater fall in processed peptide versus prohormone levels. CSF ß-MSH and ß-MSH/POMC remained suppressed by 31% and 29% 1-year after surgery (<i>p</i> &lt; .0001). Plasma AgRP increased after diet (<i>p</i> &lt; .001) and initially after surgery (<i>p</i> = .08) but not at 1-year. CSF AgRP was initially unchanged but increased 1-year after surgery (<i>p</i> &lt; .05); the ratio of ß-MSH/AgRP in plasma and CSF decreased by 29% and 40% reflecting an overall fall in melanocortin activity. In conclusion WL is maintained after bariatric surgery despite counterregulatory changes in leptin and melanocortin activity similar to diet that would be expected to stimulate weight regain.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural correlates of maternal empathy as a function of childhood emotional abuse history","authors":"James E. Swain,&nbsp;S. Shaun Ho,&nbsp;Katherine Guyon-Harris,&nbsp;Sarah Ahlfs-Dunn,&nbsp;Jerrica Pitzen,&nbsp;Jessica Riggs,&nbsp;Jason Amadio,&nbsp;Elle Eggers,&nbsp;Alissa Huth-Bocks","doi":"10.1111/jne.70295","DOIUrl":"10.1111/jne.70295","url":null,"abstract":"<p>Childhood emotional abuse (CEA) has enduring effects on health and close relationships, including parenting. Mothers with maltreatment histories often experience parenting difficulties, yet research has primarily focused on physical and sexual abuse. Far less is known about how CEA influences maternal brain responses during parenting. Prior studies suggest atypical neural activity among at-risk mothers when viewing or hearing their own children. This study examined associations between maternal CEA and neural responses during a Child Face Mirroring Task (CFMT), an fMRI paradigm assessing maternal empathy toward child emotions, a key component of sensitive parenting. Fourteen low-income mothers (mean age = 32 years) with self-reported trauma exposures from a longitudinal parenting study completed CFMT scanning when their children were age 5. Mothers viewed images of their own and unknown children expressing neutral, ambiguous, distressful, or joyful emotions. Before each block, mothers were instructed to either “join” (empathize and imitate) or “observe” (remain neutral). The Join-Own-Child &gt; Observe-Own-Child contrast was regressed against maternal CEA severity (Childhood Trauma Questionnaire). Whole-brain analyses were corrected for multiple comparisons. The Join-Own-Child &gt; Observe-Own-Child contrast activated the supplementary motor area (SMA) and right pericentral gyrus (pCG). Higher CEA scores were associated with greater activation in SMA, dorsomedial prefrontal cortex (dmPFC), periaqueductal gray (PAG), middle cingulate cortex (MCC), left temporal pole, and right inferior temporal gyrus—but not pCG. Meta-analytic mapping indicated these regions support belief-based mentalization (i.e., the consideration of others' emotional or mental states), pain, and autobiographical memory processes. Maternal CEA was linked to heightened engagement of brain regions involved in top-down mentalization rather than sensorimotor imitation. Such over-mentalization (i.e., explaining away intentions and feelings of another person), and memory-linked processing may influence mothers' interpretations of their children's emotions, potentially impairing sensitivity. Understanding these neural mechanisms may inform therapeutic strategies to improve parenting among mothers with emotional abuse histories.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute ayahuasca administration attenuates binge-like eating and anxiety-related behaviors in mice subjected to intermittent fasting","authors":"Cristian Ferreira Corona,&nbsp;Felipe Alves Alencar Lima,&nbsp;Jessica Sabrina Canedo da Silva Sumensse,&nbsp;Kevin Donansan Carvalho,&nbsp;Pedro Henrique Grignet,&nbsp;Heloisa Deola Confortim,&nbsp;Maria Claudia Gross,&nbsp;Fabiana Aidar Firmino,&nbsp;Fernanda Ferreira Evangelista,&nbsp;Francisney Pinto Nascimento,&nbsp;Jean Franciesco Vettorazzi","doi":"10.1111/jne.70290","DOIUrl":"https://doi.org/10.1111/jne.70290","url":null,"abstract":"<p>Human binge eating disorder is characterized by recurrent episodes of excessive food consumption accompanied by loss of control and is strongly associated with alterations in reward processing and emotional regulation. Ayahuasca, a psychoactive botanical preparation traditionally used in Amazonian medicine, has been shown to modulate serotonergic signaling and reward-related behaviors and has emerged as a potential therapeutic tool for mood and substance use disorders. However, its effects on binge-like eating behavior remain largely unexplored. In the present study, we evaluated the behavioral and metabolic consequences of a binge-like eating model in mice and investigated the effects of a single administration of ayahuasca on food intake, sucrose consumption, and anxiety-like behavior. Male C57BL/6 mice were subjected to an intermittent fasting protocol combined with restricted access to a standard diet and a sucrose solution for 10 days. On the eleventh day, a subgroup of binge-exposed mice received a single oral dose of ayahuasca (1.76 mg/kg of N, N-dimethyltryptamine). Food and sucrose intake were quantified during refeeding periods; anxiety-like behavior was assessed using the elevated plus maze; and the expression of hypothalamic genes POMC and CART was evaluated by RT-PCR. Mice exposed to the binge-like eating protocol exhibited increased food and sucrose intake during restricted access periods, reduced body weight, anxiogenic-like behavior, and reduced hypothalamic CART gene expression. Ayahuasca administration selectively reduced food and sucrose intake during the initial hour of refeeding without affecting later intake, reversed anxiety-like behavior, and increased hypothalamic CART expression. These findings support the notion that ayahuasca acutely attenuates binge-like eating and anxiety-related behaviors in mice, supporting its potential relevance for investigating psychedelic-based approaches targeting compulsive eating and associated emotional dysregulation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam: A tribute to Marie J. Gibson, PhD","authors":"Rae Silver,&nbsp;Eric Bittman,&nbsp;Michael Lehman,&nbsp;Sandra K. Masur,&nbsp;Kazue Semba,&nbsp;T. John Wu","doi":"10.1111/jne.70277","DOIUrl":"10.1111/jne.70277","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling identifies candidate biomarkers for small intestinal neuroendocrine tumours G1 and G2","authors":"Malin Grönberg,&nbsp;Dimitrios Papantoniou,&nbsp;Eva Tiensuu Janson","doi":"10.1111/jne.70289","DOIUrl":"https://doi.org/10.1111/jne.70289","url":null,"abstract":"<p>Although small intestinal neuroendocrine tumours (SI-NET) Grade 1 (G1) and 2 (G2) are often studied together, clinical course and response to treatment may differ. We hypothesized that these tumour groups express different markers in blood that may inform future treatment strategies. Blood from 107 SI-NET patients (G1 n = 64, G2 n = 43) and 50 healthy controls was analysed with proximity extension assay (Olink, Uppsala, Sweden). Two oncology protein panels were used. Outcomes were analysed with regression analysis and machine learning algorithms (Random Forest, Boruta). In age-adjusted analyses, 188 proteins differed between patients and healthy controls, with most being elevated in patients. Six proteins were elevated in G2 vs. G1 patients. After adjusting for age, Retbindin (RTBDN), Cryptic family protein 1 (CFC1), and Calbindin 1 (CALB1) remained significant, while adjusting for age and stage left only RTBDN significant. In a stage IV-restricted analysis, RTBDN was higher in G2 than in G1 (estimate 1.688; 95% CI 0.796–2.580; <i>p</i> &lt;0.001). RTBDN and Midkine (MDK) were associated with poor survival, whereas the opposite was seen for Integrin subunit alpha V (ITGAV). RTBDN emerged as the only candidate biomarker associated with tumour grade after adjustment for age and stage in the G1/G2 analysis. In the stage IV-restricted analysis, RTBDN remained the top-ranked protein and showed a similar direction of association without reaching the strict Bonferroni-adjusted significance threshold. Higher RTBDN levels were also associated with increased mortality risk. These findings are exploratory and require independent validation before clinical application.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cushing's syndrome is associated with an advanced chronotype","authors":"Hanna Nowotny,&nbsp;Adriana Albani,&nbsp;Mina Mazari,&nbsp;Stephanie Zopp,&nbsp;Martha Merrow,&nbsp;Nicole Reisch,&nbsp;Luis Gustavo Perez-Rivas,&nbsp;Marily Theodoropoulou","doi":"10.1111/jne.70286","DOIUrl":"10.1111/jne.70286","url":null,"abstract":"<p>Cushing's syndrome is characterised by chronic glucocorticoid excess that abolishes the physiological circadian cortisol rhythm. We investigated whether this circadian disruption alters chronotype. In a single-centre case–control study, chronotype was assessed using the Munich ChronoType Questionnaire (MCTQ; <i>n</i> = 119) and wrist actigraphy (<i>n</i> = 39) in patients with active Cushing's syndrome, patients in biochemical remission, and healthy controls. The primary outcome was mid-sleep on free days corrected for sleep debt (MSFsc). Multivariable analysis was performed to identify independent predictors of chronotype. Agreement between methods was assessed by Bland–Altman analysis. Patients with active Cushing's syndrome had a significantly earlier chronotype than patients in remission and controls (MSFsc by MCTQ: 2.38 h [IQR 1.22; 3.41] vs. 3.29 h [IQR 2.65; 4.32] vs. 3.73 h [IQR 3.16; 4.08]; <i>p</i> = .007 and <i>p</i> = .0003, respectively; actigraphy: 3.15 ± 0.90 h vs. 4.03 ± 0.96 h vs. 4.46 ± 0.75 h; <i>p</i> = .039 and <i>p</i> = .001, respectively). Chronotype did not differ significantly between patients in remission and controls. In a multivariable quantile regression model, active Cushing's syndrome was an independent predictor of chronotype (1.32 h earlier than controls; <i>p</i> = .049), while age, BMI, psychiatric symptoms and sleep disturbance had no significant influence. Actigraphy confirmed earlier sleep offset and acrophase in active Cushing's syndrome. MCTQ and actigraphy were significantly correlated (Pearson <i>r</i> = 0.619, <i>p</i> = .0003, <i>n</i> = 29); agreement analysis revealed no systematic bias, but a significant proportional bias, reflecting wider dispersion of MCTQ-derived values. Patients with active Cushing's syndrome have an earlier chronotype than patients in remission and healthy controls, as determined by both subjective and objective methods. Chronotype assessment, particularly with the MCTQ, may complement biochemical monitoring.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.70286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropeptides and their receptors in CNS cancer imaging/theranostics: Review of recent advances and increased interest with emphasis on the somatostatin/bombesin/substance P peptide receptor families","authors":"Terry W. Moody,&nbsp;Irene Ramos-Alvarez,&nbsp;Robert T. Jensen","doi":"10.1111/jne.70287","DOIUrl":"10.1111/jne.70287","url":null,"abstract":"<p>This paper includes a summary of the main points of our recent presentation at the 2025 RegPep meeting in Washington, DC. In the invitation to make this presentation by the meeting organizers, we were asked to include a discussion of peptide directed imaging and theranostics to areas that would be of interest to the attendees, which primarily includes studies related to the CNS. The interest in the possible application of peptide theranostics to oncology both generally and in the case of the CNS tumors has markedly increased over the last few years because of its successful application in both neuroendocrine tumors and prostate cancer, leading to FDA approved novel tumor approaches for both imaging these tumors as well as for its theranostic approach. In this paper we review the scientific basis for the successful application of peptide theranostics to neuroendocrine and prostate cancer, and the current status of its application to CNS tumors, particularly meningiomas, glioblastomas including glioblastoma multiforme, and medulloblastomas. We particularly concentrate on the possible use of the somatostatin, bombesin (Bn), and substance P (SP)/neurokinin (NK) family of receptors as targets, which have received the most attention and show the most promise in applying peptide receptor imaging/theranostics to CNS tumors. We also discuss the specific problems that the CNS presents in applying this approach to CNS tumors because of the blood–brain barrier in addition to the progress made. Clinical Trial Registry: NCT01578239 (NETTER-1)(NET), NCT03972488 (NETTER-2)(NET): VISION Trial (NCT03511664)[Lu-177-PSMA-617] (Pluvicto) in advanced prostate cancer.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In memoriam: Professor Robert P. (‘Bob’) Millar (1944–2026)","authors":"Wouter W. de Herder,&nbsp;Michael N. Lehman,&nbsp;Krystallenia I. Alexandraki,&nbsp;Robert L. Goodman,&nbsp;Ashley B. Grossman,&nbsp;Suzanne L. Dickson,&nbsp;Mike Ludwig,&nbsp;Julian G. Mercer,&nbsp;Claire L. Newton,&nbsp;Sue Thorn","doi":"10.1111/jne.70285","DOIUrl":"https://doi.org/10.1111/jne.70285","url":null,"abstract":"","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early neuroendocrine signatures of polyendocrine metabolic ovarian syndrome risk: Pubertal programming, social brain signals, and novel therapeutic targets","authors":"Seda Hanife Oğuz,&nbsp;Bülent Okan Yildiz","doi":"10.1111/jne.70284","DOIUrl":"10.1111/jne.70284","url":null,"abstract":"<p>Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is increasingly recognized as a disorder with developmental origins, yet its early neuroendocrine antecedents during puberty remain poorly understood. While most diagnostic frameworks apply post-menarche, growing evidence suggests that PMOS risk may be programmed well before clinical onset through alterations in central neuroendocrine pathways that emerge during the pubertal transition. In this review, we examine the concept of pubertal neuroendocrine programming in girls at risk for PMOS, with a particular focus on kisspeptin-GnRH dysregulation, central metabolic signaling, and the emerging role of oxytocin in modulating reproductive and behavioral outcomes. We propose that early disturbances in the integration of reproductive, metabolic, and social neuroendocrine circuits contribute to the trajectory toward PMOS. Special attention is given to the “social brain,” including oxytocinergic pathways, which may influence stress sensitivity, emotional eating, and pubertal tempo; underexplored but potentially modifiable dimensions of PMOS risk. By synthesizing data from basic science, translational models, and adolescent cohorts, we outline neuroendocrine signatures of early PMOS vulnerability and evaluate their potential as biomarkers and therapeutic targets. Finally, we discuss opportunities for intervention during the pubertal window, including lifestyle, behavioral, and central nervous system-targeted therapies. Understanding how the brain orchestrates puberty in at-risk individuals may unlock new strategies for preventing PMOS before it fully manifests, shifting the clinical focus from late diagnosis to early modulation.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy of standard-dose versus reduced-dose everolimus in patients with advanced neuroendocrine tumors: A multicenter retrospective cohort study","authors":"Oudai Sahwan,&nbsp;Amr Mohamed,&nbsp;Fares Jamal,&nbsp;Abdullah Alsulaiman,&nbsp;Jennah J. Bauernfeind,&nbsp;Katherine Myers,&nbsp;Patrick McGarrah,&nbsp;Timothy J. Hobday,&nbsp;Jason Starr,&nbsp;Thorvardur Halfdanarson,&nbsp;Mohamad Bassam Sonbol","doi":"10.1111/jne.70278","DOIUrl":"10.1111/jne.70278","url":null,"abstract":"<p>Everolimus 10 mg daily is the standard dose for advanced neuroendocrine tumors (NETs), but adverse events frequently necessitate dose reduction. As a result, oncologists often adopt a dose-escalation strategy starting at 5 mg and increasing the dose as tolerated. In this multicenter study, we evaluated the effect of reduced dose (RD) and standard dose (SD) everolimus on survival, progression, and toxicity in patients with advanced NETs. We conducted a multicenter retrospective cohort study of patients with advanced NETs treated with everolimus at Mayo Clinic and University Hospitals (Cleveland, OH). Patients were grouped by starting dose (5 mg vs. 10 mg). Primary endpoints were overall survival (OS), real-world progression-free survival (rwPFS), and adverse events. Multivariable Cox models, inverse probability of treatment weighting (IPTW), and time-varying dose sensitivity analysis were used to account for confounding and dose crossover. Among 170 patients (48 started on 5 mg; 122 on 10 mg), the 5 mg cohort was older, had worse ECOG PS, and was more heavily pretreated. Median OS was 43.7 months (5 mg) versus 81.5 months (10 mg; log-rank <i>p</i> = .02). However, after multivariable adjustment (<i>N</i> = 124 G1–G2 patients; 51 events), the association was no longer statistically significant (adjusted HR, 0.59; 95% CI, 0.31–1.12; <i>p</i> = .11). Median rwPFS was 7.0 versus 12.4 months (log-rank <i>p</i> = .05); the adjusted rwPFS difference was not statistically significant (HR, 0.95; 95% CI, 0.56–1.61; <i>p</i> = .84). Nearly half (46.7%) of 10 mg starters required dose reduction. Any-grade toxicity was more common with 10 mg (89% vs. 75%; <i>p</i> = .05). The apparent survival advantage of standard-dose everolimus was substantially attenuated after adjustment. These findings do not establish dose equivalence and should be interpreted in the context of limited statistical power. Given its more favorable observed tolerability profile, RD everolimus warrants prospective evaluation as a starting strategy for patients at increased risk of treatment-related toxicity who may not tolerate SD.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 10","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}