Endocrine oncology (Bristol, England)最新文献

{"title":"Comprehensive Somatic Profiling of Gastroenteropancreatic Neuroendocrine Neoplasms.","authors":"Chirayu Mohindroo, Parul Agarwal, Valerie Lee, Jin He, Robert Anders, Katherine Bever, Daniel Laheru, Ana De Jesus-Acosta","doi":"10.1530/EO-26-0044","DOIUrl":"10.1530/EO-26-0044","url":null,"abstract":"<p><strong>Background: </strong>The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is rising, yet their biological heterogeneity and variable response to treatments remain poorly understood. Comprehensive genomic characterization may uncover somatic drivers and inform biomarker-driven therapeutic strategies.</p><p><strong>Methods: </strong>We retrospectively analyzed clinically ordered next-generation sequencing (NGS) results from tumor samples of 111 patients with confirmed GEP-NENs treated at Johns Hopkins Hospital between 2020 and 2022. Pathogenic and likely pathogenic mutations were identified using OncoKB, CHASMplus, and COSMIC databases. Mutational patterns were correlated with clinical characteristics and overall survival using univariate and multivariate analyses.</p><p><strong>Results: </strong>In this retrospective study of 111 patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), somatic pathogenic or likely pathogenic mutations were identified in 79% of cases. The most frequent alterations involved TP53 (19%), MEN1 (17%), and chromatin remodeling genes such as DAXX (9%) and ATRX (6%). Notably, we also identified a subset of patients (9%) patients with mutations typically associated with hematologic malignancies. Distinct co-mutation and mutual exclusivity patterns were observed between pancreatic and non-pancreatic NENs. Poorly differentiated or high-grade tumors correlated with mutations in TP53, KRAS, and CDKN2A. Mutations in KRAS, DAXX/ATRX, and hematologic malignancy-associated genes were independently associated with worse overall survival.</p><p><strong>Conclusions: </strong>This study reveals distinct somatic mutation patterns in GEP-NENs associated with tumor differentiation, grade, primary site, and survival. The identification of hematologic malignancy-associated mutations in a subset of GEP-NENs suggests possible shared molecular phenotypes with poor prognostic implications. The presence of KRAS mutations supports exploring pan-RAS inhibitors as potential therapies in select patients. These findings highlight the clinical utility of genomic profiling in GEP-NENs.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond mitotane: next-generation therapeutic landscapes in adrenocortical carcinoma.","authors":"Keya Kotecha, Katia Mariniello, Leonardo Guasti","doi":"10.1530/EO-26-0040","DOIUrl":"10.1530/EO-26-0040","url":null,"abstract":"<p><p>The clinical management of adrenocortical carcinoma (ACC) has long been defined by its resistance to conventional therapies. Since the FIRM-ACT trial established the combination of etoposide, doxorubicin, and cisplatin plus mitotane (EDP-M) as the frontline standard, overall survival for metastatic patients has remained stubbornly low. This plateau in efficacy with cytotoxic regimes has necessitated a shift towards precision oncology and immunotherapy. However, translating the success of immune checkpoint inhibitors seen in other malignancies to ACC has proven exceptionally difficult. The primary challenge in the present therapeutic landscape of immunotherapy is the unique biology of the adrenal cortex, which creates an intrinsic immunologically privileged site. This review will address these current immunological hurdles but also explore novel strategies designed to bypass this barrier entirely. By shifting focus towards mechanisms that do not solely rely on the traditional engagement of adaptive immune system - such as the targeted delivery of cytotoxic payloads via antibody-drug conjugates (ADCs) or the androgen-mediated activation of myeloid cells to clear pro-tumoural populations - the field is moving towards a future where the 'cold' nature of the tumour microenvironment may no longer dictate the limits of therapeutic success.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260040"},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytological biomarkers and risk of malignancy in indeterminate thyroid nodules: a systematic review and meta-analysis.","authors":"Trille Moberg Fagerhaug, Mathilde Hvidtfelt Kjeldsen, Mathias Maagaard, Preben Homøe, Gitte Bjørn Hvilsom","doi":"10.1530/EO-25-0097","DOIUrl":"10.1530/EO-25-0097","url":null,"abstract":"<p><strong>Purpose: </strong>Thyroid nodules with indeterminate cytology are often referred for diagnostic surgery. This systematic review evaluated diagnostic markers in fine-needle aspiration cytology samples of indeterminate nodules to improve differentiation between benign and malignant nodules.</p><p><strong>Methods: </strong>We searched MEDLINE, Embase, and the Cochrane Library from 1995 to 2025. The literature was screened, and data were extracted from the included studies. The quality of studies was assessed with QUADAS-2. We performed split component meta-analysis of diagnostic accuracy using R-studios and the SCS meta-function (split component synthesis).</p><p><strong>Results: </strong>Forty-one relevant studies were identified, of which 23 eligible studies were included in the meta-analysis. Data on Galectin-3, HBME-1, and BRAF mutation from 1,564 patients were evaluated. Galectin-3 and HBME-1 demonstrated promising diagnostic accuracy, with diagnostic odds ratios (DORs) of 20.3 (95% CI: 9.7-42.5) and 15.0 (95% CI: 7.3-31.0), sensitivities of 0.74 (95% CI: 0.64-0.82) and 0.77 (95% CI: 0.67-0.84), and specificities of 0.88 (95% CI: 0.80-0.93) and 0.82 (95% CI: 0.73-0.89), respectively. Combined positivity yielded the highest DOR of 45.8 (95% CI: 17.7-118.6), sensitivity of 0.90 (95% CI: 0.81-0.95), and specificity of 0.84 (95% CI: 0.73-0.91). BRAF mutation had the lowest DOR of 6.6 (95% CI: 2.1-20.4) and sensitivity of 0.17 (95% CI: 0.09-0.29) but the highest specificity of 0.97 (95% CI: 0.93-0.99).</p><p><strong>Conclusion: </strong>Our meta-analysis indicates that Galectin-3 and HBME-1, particularly when combined, may improve differentiation between benign and malignant nodules. BRAF mutation is highly specific but lacks sensitivity. These biomarkers show potential, but none warrant stand-alone clinical use, emphasizing the need for large-scale validation and potentially a multi-marker approach to improve diagnostic accuracy.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250097"},"PeriodicalIF":0.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticotroph Tumour Progression 37 Years After Bilateral Adrenalectomy with Temozolomide-Naive Response to Pembrolizumab.","authors":"Edward Mignone, Luke Ephraums, Ian Chapman, Esther Quick, Sunita M C De Sousa, Jui Ho","doi":"10.1530/EO-26-0064","DOIUrl":"10.1530/EO-26-0064","url":null,"abstract":"<p><strong>Summary: </strong>Corticotroph tumour progression (CTP) following bilateral adrenalectomy for Cushing's disease usually emerges within the first decade; substantially delayed presentations are uncommon and longer term surveillance recommendations remain imprecise. We report a patient presenting with CTP 37 years after adrenalectomy, representing one of the latest onset cases in the literature. Tumour profiling demonstrated an aggressive molecular phenotype including ATRX loss, MEN1 inactivation and CDK4 amplification, with a Ki-67 index of 10% and absent PD-L1 expression. Pembrolizumab, administered for a concurrent metastatic melanoma, was associated with a rapid and sustained biochemical and radiological response, making this the fifth reported case of CTP post-adrenalectomy responding to immune checkpoint inhibitor (ICI) therapy and notably the first without prior temozolomide exposure. This case illustrates three clinically relevant points: 1. lifelong post-adrenalectomy surveillance requires a structured long-term framework; 2. comprehensive molecular profiling of aggressive corticotroph tumours may inform prognosis and facilitate access to targeted therapies; and 3. ICI response in corticotrophinomas may occur despite PD-L1 negativity and without temozolomide-induced hypermutation, supporting the rationale for evaluating earlier immunotherapy in this biologically distinct subtype.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SDHB and CDK1 protein expression in metastatic pheochromocytoma and paraganglioma.","authors":"Lisa Gunnesson, Sinan Karakaya, Sofie Mohlin, Andreas Muth, Erik Elias","doi":"10.1530/EO-26-0035","DOIUrl":"10.1530/EO-26-0035","url":null,"abstract":"<p><strong>Background: </strong>Pheochromocytomas and paragangliomas (PPGLs) are rare and mostly non-metastatic tumors originating from adrenal medulla and paraganglia. Metastatic PGLs have a worse prognosis, but currently, there are no established criteria to determine PPGL metastatic potential.</p><p><strong>Aim: </strong>The aim of this study was to investigate whether SDHB and CDK1 expression is associated with metastatic capacity in PPGL.</p><p><strong>Material and methods: </strong>A tissue microarray (TMA) was constructed from 175 tumors from a total of 149 unique PPGL patients treated at Sahlgrenska University Hospital. SDHB, CDK1, and proliferation index Ki-67 were assessed and correlated to metastatic capacity defined as a confirmed metastatic event.</p><p><strong>Results: </strong>Negative SDHB expression was more common in patients with metastatic PPGL and displayed a trend toward lower overall survival and correlation with higher Ki-67%. High CDK1 expression was not associated with any of the parameters mentioned above.</p><p><strong>Conclusion: </strong>Negative SDHB expression but not high CDK1 expression is associated with metastatic capacity in PPGL.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260035"},"PeriodicalIF":0.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematological neoplasms after PRRT: experience from long term follow-up of 173 patients in a tertiary center.","authors":"Joao Pedro Thimotheo Batista, Michael De La Iglesia, Hyun Kim, Vikas Prasad, Ravindra Shubha, Rama Suresh, Shuang Wu, Jingxia Liu, Meagan Jacoby, Samuel Urrutia, Nikolaos A Trikalinos","doi":"10.1530/EO-26-0038","DOIUrl":"10.1530/EO-26-0038","url":null,"abstract":"<p><strong>Objective: </strong>Peptide receptor radionuclide therapy (PRRT) with lutetium-177 DOTATATE (¹⁷⁷Lu-DOTATATE) is widely adopted as a later-line treatment (second-line or subsequent therapy) for patients with somatostatin receptor-positive neuroendocrine neoplasm. The registration NETTER-1 trial reported a late-onset adverse event of therapy-related myeloid neoplasms (tMNs), including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) in approximately 1% of patients. In this retrospective study, we sought to investigate the frequency of tMN in patients treated with ¹⁷⁷Lu-DOTATATE at our institution over the last 8 years and determine the treatment characteristics of patients developing tMN.</p><p><strong>Methods: </strong>We accessed the treatment files of patients with neuroendocrine neoplasms treated at our institution between January 2017 and January 2025 for pathology reports of myelodysplasia, leukemia, aplastic anemia and similar hematological disorders.</p><p><strong>Results: </strong>A total of 173 patients received ¹⁷⁷Lu-DOTATATE. A vast majority (77.5%) of them were treated with four therapy cycles. A total of 10/173 (5.8%) patients (4 males, 6 females) were diagnosed with tMN at a median of 23 months (5.63) after first cycle. One patient developed severe thrombocytopenia, stopped all treatments and was lost to follow-up. Two patients developed acute myelogenous leukemia (AML), six developed myelodysplastic syndrome (MDS), one developed aplastic anemia, and one developed multilineage dyspoiesis (the latter two also deemed to have MDS). Eight out of ten (80%) died after a median duration of 8 months (4.23) from tMN diagnosis. Two patients were diagnosed with AML after 2 and 4 years from the start of first cycle, while 40% of MDS cases were diagnosed by 1 year after cycle 1 of ¹⁷⁷Lu-DOTATATE. Additionally, multilineage dyspoiesis was observed at around 5 years.</p><p><strong>Conclusions: </strong>The prevalence of tMN was 5.8% in our patient population. We have noted a higher than previously reported percentage of myelodysplasia post-PRRT, especially with additional treatments and longer follow-ups.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260038"},"PeriodicalIF":0.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parathyroid carcinoma: epidemiology and genetics.","authors":"Daniela Betea, Patrick Petrossians","doi":"10.1530/EO-25-0104","DOIUrl":"10.1530/EO-25-0104","url":null,"abstract":"<p><p>Primary hyperparathyroidism (PHPT), considered a rare disease almost a century ago, has shown a notable increase in incidence over the past five decades, driven largely by improved diagnostic screening and greater clinical awareness. Following the same trend, the incidence of parathyroid carcinoma (PC), a very rare but aggressive malignancy accounting for approximately 1% of PHPT cases, appears to be rising. This increase parallels the overall rise in PHPT detection, suggesting that enhanced surveillance contributes to identifying more PC cases. PC is mostly characterized by severe hypercalcaemia, due to tumoral parathyroid hormone (PTH) over-secretion and a high rate of local recurrence and metastasis, making early diagnosis and surgical treatment crucial. Recent advances in genetics and epigenetics have profoundly expanded our understanding of PC pathogenesis. Germline and somatic mutations in the tumour suppressor gene <i>CDC73</i> (encoding parafibromin) are implicated in up to 75% of familial and sporadic PC cases. Additional recurrent mutations in genes such as <i>MEN1</i> and <i>PRUNE2</i>, alterations in cell cycle regulators such as <i>CCND1</i> and <i>EZH2</i>, and disruptions in signalling pathways including PI3K/AKT/mTOR have been identified. Epigenetic modifications, including microRNA expression changes and promoter hypermethylation, also play a significant role in tumour development and progression. This mini review synthesizes epidemiological trends demonstrating an increasing incidence of PC following the rise of PHPT and highlights pivotal genetic and epigenetic findings contributing to tumourigenesis. Integrating new molecular insights with advances in clinical surveillance offers promise for improved diagnosis, prognostic stratification, and the development of future targeted therapies for parathyroid carcinoma.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250104"},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CHEK2</i> germline gene variant in a patient with a somatotrophinoma and primary hyperparathyroidism: a novel MEN1-like syndrome?","authors":"Durairaj Arjunan, Mohammad Hayat Bhat, Ashutosh Rai, Vaishali Kaur, Sayka Barry, Md Ejaz Alam, Mohammad Salem Baba, Ajay Gulati, Debajyoti Chatterjee, Manzoor Ahmad Latoo, Márta Korbonits, Ashley B Grossman, Pinaki Dutta","doi":"10.1530/EO-25-0100","DOIUrl":"10.1530/EO-25-0100","url":null,"abstract":"<p><strong>Context: </strong>Somatotrophinomas can occasionally occur in familial settings and may be associated with known germline mutations, such as <i>MEN1, AIP, CDKN1B, PRKAR1A, SDHx,</i> and <i>MAX</i>. Recently, the <i>CHEK2</i> gene has emerged as a potential pituitary tumour predisposition gene.</p><p><strong>Objective: </strong>To present a rare case of a patient with a pituitary somatotrophinoma and primary hyperparathyroidism (PHPT) associated with a likely pathogenic <i>CHEK2</i> germline mutation, suggesting a novel MEN1-like phenotype.</p><p><strong>Methods: </strong>We conducted a detailed clinical, biochemical, radiological, and genetic evaluation of a 38-year-old woman presenting with features of acromegaly and PHPT. Genetic testing for known MEN1 syndrome-associated genes and broader pituitary tumour predisposition genes was performed.</p><p><strong>Results: </strong>The patient presented with features of acromegaly of 3 years duration and a collagenoma. Laboratory evaluation revealed an elevated IGF-1. Biochemical and imaging studies also revealed PTH-dependent hypercalcaemia and bilateral inferior parathyroid adenomas. Genetic testing for a panel of genes causing hypercalcaemia - including <i>MEN1</i> and <i>CDKN1B</i> - was negative; however, a pathogenic nonsense variant in <i>CHEK2</i> (c.232C>T; p.(Gln78Ter); gnomAD frequency: 0.0006%) was detected with exome sequencing. The patient underwent transsphenoidal resection of the pituitary tumour followed by gamma-knife radiosurgery and received long-acting octreotide every four weeks. Parathyroidectomy was performed 1.5 years later.</p><p><strong>Conclusion: </strong>This is the first reported case of a <i>CHEK2</i> germline mutation associated with somatotrophinoma, PHPT, and collagenoma, mimicking the clinical MEN1 syndrome. These findings expand the spectrum of possible <i>CHEK2</i>-associated neoplasia and highlight the need to consider <i>CHEK2</i> as a possible candidate gene in patients with MEN1-like syndromes when common mutations have been excluded.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250100"},"PeriodicalIF":0.0,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin modifies hormone changes associated with androgen deprivation therapy for prostate cancer.","authors":"Mathew Gorman, Nawaid Usmani, Michael N Pollak, Sunita Ghosh, Arun Elangovan, Julian Kim, John Thoms, Myriam Bouchard, Michael Peacock, Ye Wang, Neil E Fleshner, Holly Campbell, Eric Vigneault, Francois Vincent, Alan So, Fabio L Cury, Harvey C Quon, Ryan G Carlson, Carole Lambert, Laurence Klotz, Kim Chi, Michael Brundage, Kerry S Courneya, Bernhard J Eigl","doi":"10.1530/EO-25-0114","DOIUrl":"10.1530/EO-25-0114","url":null,"abstract":"<p><p>Androgen deprivation therapy (ADT) is regularly used to treat locally advanced and metastatic prostate cancer (PCa) with toxicities, including metabolic syndrome (MS) and associated adverse hormonal changes. This study evaluated whether metformin mitigates changes in laboratory biomarkers associated with MS and type II diabetes mellitus (T2DM) in PCa patients receiving ADT. PRIME is a phase III double-blind, randomized controlled trial in which 166 normoglycemic patients with PCa receiving ADT were randomized to receive metformin or placebo. For this study, 47 patients from the metformin arm and 32 patients from the placebo arm underwent serum collection and analysis of the following analytes at baseline, 9, and 12 months: IGF-1, IGFBP1, IGFBP2, IGFBP3, IGFBP7, leptin, adiponectin, GDF15, insulin, C-peptide, GIP, GLP-1, and IL-6. Independent <i>t</i>-tests were used to determine whether significant changes in analytes were evident in patients receiving metformin vs placebo and to evaluate analyte changes from baseline for the metformin and placebo groups separately. Mean leptin values increased markedly in the placebo group and significantly less in the metformin group across all time points. Significant improvements were also observed in IGFBP1, IL-6, C-peptide, and GLP-1 with metformin compared with placebo. GDF15 and IGFBP3 significantly increased compared with baseline with ADT alone. This study demonstrates that metformin can mitigate biomarker changes induced by ADT associated with an increased risk of T2DM and MS. In addition, the attenuated increase in leptin signals a potential for improved PCa outcomes, as high leptin values have been correlated with aggressive disease and worse prognosis.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250114"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional and behavioral outcomes in pediatric adrenal carcinoma under mitotane therapy: a caregiver-reported pilot study.","authors":"Heidi Frey, Maria Riedmeier, Johanna Krüger, Carl Friedrich Classen, Nerea Domínguez-Pinilla, Maria Fragoso, Steffen Fuchs, Dominika Janus, Mouna Mezoued, Andrea Mocna, Jessica Munarin, Soraya Puglisi, Hilal Susam Sen, Gerdi Tuli, Justyna Walenciak, Bilgehan Yalcin, Martin Fassnacht, Verena Wiegering","doi":"10.1530/EO-26-0010","DOIUrl":"10.1530/EO-26-0010","url":null,"abstract":"<p><strong>Objective: </strong>Mitotane is the standard therapy for advanced pediatric adrenocortical carcinoma (pACC). With improving survival, treatment-related long-term side effects and their impact on everyday functioning are becoming increasingly relevant. This multicenter pilot study provides first insights into this underexplored topic and lays the groundwork for future prospective investigations.</p><p><strong>Design and methods: </strong>Caregivers of children with pACC treated with mitotane completed an online questionnaire. Based on these retrospective caregiver-reported data, treatment-related side effects and growth parameters were assessed. Using two validated instruments - Child and Adolescent Scale of Participation (CASP) and Strengths and Difficulties Questionnaire (SDQ) - caregivers rated functional participation and behavioral outcomes. We classified patients according to ongoing versus completed mitotane therapy and compared them with a sibling control group.</p><p><strong>Results: </strong>The cohort included 24 children with pACC from eight countries, predominantly with advanced tumors (stage III-IV: 66.7%, median age: 7.4 years, 41.7% females). Half had completed mitotane therapy, and half were still receiving it. Most patients experienced relevant side effects, with adrenal insufficiency being the most frequent ongoing limitation. Patients on ongoing mitotane therapy showed reduced functional participation and more pronounced behavioral difficulties, whereas those who had completed therapy had outcomes comparable to their siblings.</p><p><strong>Conclusion: </strong>The findings of this pilot study suggest temporary impairments in functional participation and psychosocial behavior during mitotane treatment, with improvement after therapy completion. In contrast, endocrine sequelae, particularly adrenal insufficiency, may persist beyond treatment. These observations underscore the need for standardized long-term endocrine follow-up and support the feasibility of larger, prospective studies to evaluate long-term neuropsychological outcome, especially in younger children.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260010"},"PeriodicalIF":0.0,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}