Endocrine-related cancer最新文献

{"title":"The role of stem cells in pituitary tumour formation.","authors":"James Kaufman-Cook, Bence Kövér, Cynthia L Andoniadou","doi":"10.1530/ERC-26-0171","DOIUrl":"10.1530/ERC-26-0171","url":null,"abstract":"<p><p>Pituitary tumours are intracranial neoplasms that pose significant clinical challenges due to their potential for recurrence, therapeutic resistance and resultant endocrine dysfunction and mass effects. In the normal anterior pituitary, resident pituitary stem cells (PSCs) contribute to tissue homeostasis and cellular turnover. The extent to which PSCs contribute to tumourigenesis is not known, but an increasing number of studies have been aiming to address this. In this review, we summarise current evidence implicating PSCs and tumour stem-like populations in pituitary tumour biology, including potential roles in tumour initiation, maintenance and progression. We outline practical criteria for defining tumour stem cells and evaluate findings from functional studies of human tumours, emerging single-cell and spatial transcriptomic datasets and murine lineage-tracing models. We also provide a curated overview of published single-cell RNA sequencing studies of pituitary tumours, highlighting reported stem/progenitor populations and transcriptional signatures across tumour subtypes and propose a framework for future genomic analyses. Finally, we discuss the translational implications of these findings, including the potential for targeting stem-like populations and their associated signalling pathways.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145923","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":"Hormone secretion predicts poor prognosis in lung neuroendocrine neoplasms.","authors":"Ieva Lase, Eir Löfgren, Agnes Hegedus, Malin Grönberg, Staffan Welin, Eva Tiensuu Janson","doi":"10.1530/ERC-26-0142","DOIUrl":"10.1530/ERC-26-0142","url":null,"abstract":"<p><p>Ectopic hormone secretion from neuroendocrine neoplasms in the lung (lung-NENs) is rare and poorly explored. Emerging evidence indicates that hormone-secreting NENs carry a worse prognosis. We hypothesised that ectopic hormone production and secretion in lung-NENs is a negative prognostic marker. A retrospective cohort of 167 patients with lung-NENs (121 females, median age: 68 (min-max: 15-85) years), excluding small cell lung cancer, was analysed for clinical and biochemical data and outcome. Tumour tissue was evaluated for serotonin and calcitonin expression. Among 127 patients with hormone measurements, 52 had increased levels, with 5-hydroxyindoleacetic acid (5-HIAA) predominating (n = 38), followed by calcitonin (n = 20). There was no correlation between serotonin expression in tumour tissue and elevated levels of 5-HIAA, while high calcitonin levels were strongly correlated with calcitonin expression in tumour samples (OR: 21.86, P = 0.002). Furthermore, diffuse calcitonin staining was associated with a shorter overall survival (OS) (P = 0.036). Hormone-secreting tumours had a significantly shorter OS than non-secreting tumours (62 vs 124 months, P = 0.024), and multiple hormone secretion further worsened survival (33 vs 69 vs 124 months, P = 0.002). In multivariate analysis, multiple hormone secretion remained an independent negative prognostic factor (P = 0.042). In conclusion, hormone secretion in lung-NENs is associated with a shorter OS, particularly in patients with multiple hormone secretion. Diffuse calcitonin expression in tumour tissue is an additional negative prognostic marker. We recommend routine hormone testing at baseline and at disease progression in metastatic lung-NEN patients and suggest a more intensified therapeutic strategy in cases with detectable hormone secretion.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145903","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":"Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.","authors":"Rayzel C Fernandes, Kyle K Greenland, Moray J Campbell, Charlotte L Bevan","doi":"10.1530/ERC-25-0529","DOIUrl":"10.1530/ERC-25-0529","url":null,"abstract":"<p><p>The androgen receptor (AR) is a key transcription factor in prostate cancer (PCa), whose enhanced and altered functions are known drivers of cancer progression. A key aspect of this is reprogramming of the AR cistrome, which consists of genome-wide enhancer-binding sites through which AR regulates gene expression. The magnitude and biological impact of the AR cistrome are impacted by the AR itself, including the responses to ligand, as well as the organization of the associated DNA response elements, and availability of pioneer factors, cofactors, and noncoding RNAs, all of which contribute to a functional transcription complex. In this review, we will examine, in the context of PCa progression, the factors that affect the binding of AR and its interacting partners at enhancers, with a focus on AR cistrome reprogramming. We also discuss the clinical utility of targeting the AR-enhancer nucleoprotein complex and the potential of using the AR cistrome as a prognostic tool.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13266353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058925","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":"Adrenal-derived factors drive progression of sclerotic prostate cancer in bone.","authors":"Malin Hagberg Thulin, Lei Li, Sanna Abrahamsson, Andreas Landin, Karin Horkeby, Jianyao Wu, Marie K Lagerquist, Claes Ohlsson, Matti Poutanen","doi":"10.1530/ERC-25-0309","DOIUrl":"10.1530/ERC-25-0309","url":null,"abstract":"<p><p>Bone metastasis is a leading cause of death in prostate cancer (PC) patients. Although androgen deprivation therapy (ADT) combined with novel androgen-targeted agents constitutes the cornerstone of systemic treatment, its efficacy is limited. We investigated the adrenal contribution to promoting progression of castration-resistant PC (CRPC) within bone using a preclinical intratibial xenograft model (VCaP, 22Rv1, and LNCaP cells). Mice underwent orchiectomy (ORX) to mimic ADT, with or without adrenalectomy (ORX + ADX) to eliminate adrenal contribution. A significant increase in bone mineral density (BMD) was observed in tumor-grafted tibiae in ORX-treated mice compared with controls (P < 0.001), indicating a strong tumor-induced sclerotic response. In contrast, ORX + ADX reduced tumor take rate by approximately 50% and decreased tumor-induced BMD by over 80% (P < 0.001). Transcriptomic analysis revealed that ADX downregulated tumor-induced transcripts in bone by over 90%, including osteogenic (Lox, Sparcl1, Bmp2, Postn, and Col1a1) and pro-angiogenic (Bmper, Pecam-1, and Esam) signatures. In addition, BMP, PI3K/Akt, and ERK1/2 signaling pathways were associated with the tumor-induced bone response. Both high serum progesterone and intratumoral levels of dihydrotestosterone (DHT) were associated with the sclerotic bone phenotype. ADX markedly reduced intratumoral DHT and downregulated glycolytic genes (HK2, PFK2, and LDHA) and secretory proteins expressed by the tumor, including stanniocalcin 2, potentially mediating paracrine effects in the sclerotic bone response. Altogether, these findings highlight the critical role of adrenal-dependent androgen synthesis, particularly via progesterone, in driving the sclerotic CRPC in bone. Our findings suggest that a comprehensive blockade of adrenal contribution is essential to prevent the sclerotic bone response associated with CRPC.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13261362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966056","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":"The diagnostic value of 68Ga-pentixafor PET/CT in differentiating adrenal aldosterone-producing adenomas from non-functional adenomas.","authors":"Shu Cheng, Youlin Kuang, Xiangshuang Zhang, Wei Li, Ying Jing, Hang Shen, Jiayu Li, Junlong Li, Qi Zhang, Jinbo Hu, Linqiang Ma, Ying Song, Jing Chen, Hua Pang, Qifu Li, Shumin Yang","doi":"10.1530/ERC-25-0371","DOIUrl":"10.1530/ERC-25-0371","url":null,"abstract":"<p><p>Aldosterone-producing adenoma (APA) is one of the major causes of primary aldosteronism (PA). Although 68Ga-pentixafor PET/CT has emerged as a promising tool for subtyping diagnosis of PA, its diagnostic efficacy in distinguishing APA from non-functional adrenal adenoma (NFA) remains to be evaluated. To evaluate the value of 68Ga-pentixafor PET/CT in differentiating APA from NFA, this study prospectively included patients suspicious of APA and patients diagnosed with NFA to undergo 68Ga-pentixafor PET/CT. APA was further confirmed by post-surgery histopathology and biochemical results. The diagnostic efficacy of visual analysis, maximum standardized uptake value (SUVmax) of adrenal lesions, and lateralization index of SUVmax (LI) was analyzed by receiver operating characteristic (ROC) curve. The cohort included 75 patients with APA and 51 patients with NFA. Visual analysis achieved an area under the ROC curve (AUC) of 0.84, with a sensitivity and a specificity of 0.95 and 0.73, respectively. The AUC for SUVmax and LI was 0.96 and 0.93, respectively. At an LI cutoff of 1.65, the sensitivity and specificity were both 0.87. Using an SUVmax cutoff of 7.0, the sensitivity and specificity reached 0.88 and 0.85, respectively. Visual analysis revealed a higher false-positive rate (27.27%) compared to LI (12.73%) and SUVmax (14.55%). 68Ga-pentixafor PET/CT is useful in differentiating APA from NFA; however, false-positive results remain a concern, particularly with visual analysis.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell reveals age-dependent epithelial reprogramming and EMT vulnerability in THCA.","authors":"Qiankun Zhang, Wei Pan, Xiaohua Gong, Qi Zhou","doi":"10.1530/ERC-26-0021","DOIUrl":"10.1530/ERC-26-0021","url":null,"abstract":"<p><p>Thyroid cancer exhibits pronounced cellular heterogeneity, yet the mechanisms underlying epithelial-mesenchymal transition (EMT) and tumor microenvironment (TME) remodeling remain incompletely understood. In this study, single-cell RNA sequencing of 92,849 cells from 20 thyroid tissue samples derived from underage and adult patients was performed to systematically characterize immune and epithelial heterogeneity through cell type annotation, subclustering, and functional enrichment analyses. A total of 26 distinct cell clusters were identified, encompassing immune and stromal compartments, with notable age- and stage-specific differences in T cell, epithelial, and macrophage subsets. EMT-high tumors were characterized by stromal enrichment, immune suppression, and transcriptional activation of canonical EMT drivers, including TGFB1, SNAI1/2, TWIST1/2, and ZEB1/2. Functional validation demonstrated that shRNA-mediated knockdown of PHTF2 or SNAI1 in TPC-1 and KTC-1 cell lines significantly inhibited proliferation and clonogenic capacity, accompanied by upregulation of CDH1 and downregulation of multiple EMT-associated genes. Furthermore, EMT-high tumors exhibited distinct drug sensitivity profiles, including reduced responsiveness to conventional chemotherapeutics and increased sensitivity to agents such as camptothecin and dabrafenib. Collectively, these findings identify PHTF2 and SNAI1 as key regulators of EMT and tumor cell proliferation in thyroid cancer, and suggest that EMT-driven TME remodeling contributes to immune evasion and therapeutic resistance, thereby revealing EMT-associated vulnerabilities as potential targets for precision therapy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990614","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":"Orlistat combined with everolimus suppresses pancreatic neuroendocrine tumor progression via inhibiting PI3K/AKT/mTOR signaling mediated by SLFN5.","authors":"Lin Xu, Pengfei Liu, Fengjuan Chen, Ye Tian, Lijun Yan, Jianan Bai, Xu Han, Qin Long, Xiaoya Li, Min Liu, Mujie Ye, Qiyun Tang","doi":"10.1530/ERC-25-0422","DOIUrl":"10.1530/ERC-25-0422","url":null,"abstract":"<p><p>Pancreatic neuroendocrine tumors (PanNETs) are characterized by limited therapeutic options and frequent resistance to monotherapies such as everolimus. Targeting metabolic pathways alongside mTOR signaling may improve treatment efficacy. This study aimed to investigate the synergistic antitumor effects of orlistat, a fatty acid synthase inhibitor, combined with everolimus in PanNETs and to elucidate the underlying molecular mechanisms. In vitro assays, including CCK-8, colony formation, EdU incorporation, and western blotting, were performed on PanNET cell lines. In vivo efficacy and safety were evaluated using subcutaneous xenograft mouse models. Transcriptomic profiling and functional studies of SLFN5 were conducted to uncover its regulatory role in PI3K/AKT/mTOR signaling and drug response. Orlistat and everolimus exhibited a significant synergistic inhibitory effect on PanNET cell proliferation. The combination markedly suppressed tumor growth in vivo without evident toxicity. RNA sequencing revealed distinct transcriptomic changes and highlighted SLFN5 as a key downregulated gene in PanNETs. Functional assays demonstrated that SLFN5 overexpression inhibited tumor growth and enhanced drug sensitivity by negatively regulating the PI3K/AKT/mTOR pathway. Conversely, SLFN5 knockdown impaired the antitumor efficacy of the drug combination. In conclusion, the combination of orlistat and everolimus represents a promising therapeutic strategy for PanNETs, with SLFN5 serving as a critical mediator and potential biomarker for treatment efficacy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is preoperative adrenoceptor blockade necessary in patients with paraganglioma?","authors":"Anna Angelousi, Eleni Memi, George N Zografos, Eleftherios Chatzellis, Eva Kassi, Gregory Kaltsas","doi":"10.1530/ERC-26-0007","DOIUrl":"10.1530/ERC-26-0007","url":null,"abstract":"<p><strong>Abstract: </strong>Pheochromocytomas and paragangliomas, collectively known as paragangliomas (PGLs), are rare neuroendocrine tumors originating from chromaffin cells. Surgical resection is the treatment of choice, with preoperative α-adrenoceptor blockade being consistently used prior to any surgical intervention; however, this approach has recently been challenged. This comprehensive systematic review of the literature was conducted across PubMed, Embase, and the Cochrane Library up to December 2025 to address the necessity and potential indications of α-adrenoceptor blockade in the pre-, peri-, and postoperative phase of PGL management. Papers were categorized into guidelines/consensus, meta-analyses, and clinical studies. All international guidelines uniformly recommend preoperative α-adrenoceptor blockade for functional PGLs, albeit there is no substantial evidence to support abandoning this long-standing practice. Therefore, both for medicolegal considerations and for alignment with current clinical practice, the recommendation for preoperative α-adrenoceptor blockade is still widely utilized. However, recent meta-analyses and patient cohort studies indicate no significant benefits in terms of mortality, intraoperative, or postoperative outcomes using such agents in selective patient populations. The paucity of randomized controlled trials and the recent progress in clinical practice and surgical/anesthetic techniques underscore the need for a reevaluation of the routine use of α-adrenoceptor blockade during PGL surgical resections to resolve this issue.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The secreted protein SPARCL1 suppresses tumor progression in papillary thyroid carcinoma via SLC3A2-mediated ferroptosis.","authors":"Fengping Wu, Jinkang Zhang, Xiaoli Zhang, Dongkun Xu, Shuanghua Cheng, Qian Liu, Yuxin Gan, Lifang Ren, Haocheng Yang, Kun Zhang, Xuliang Xia, Zhiqiang Jiang, Yuhong Shi, Wenling Tu","doi":"10.1530/ERC-26-0018","DOIUrl":"10.1530/ERC-26-0018","url":null,"abstract":"<p><p>Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid malignancy, where invasive growth and distant metastasis contribute to a worsened patient prognosis. SPARCL1, a known tumor suppressor gene in various cancers, encodes a secreted glycoprotein. Preliminary research suggests that elevated expression of SPARCL1 is correlated with a better prognosis in PTC, highlighting its potential as an innovative restorative therapeutic agent, but its specific role and underlying mechanisms remain unclear. This study aimed to investigate the impact of SPARCL1 on the invasion and metastasis of PTC cells by constructing an overexpression model of SPARCL1 in PTC cells through viral transduction, collecting the supernatant proteins from the PTC cell model and adding them to PTC cells, and introducing recombinant SPARCL1 protein into PTC cells. In addition, we conducted animal experiments to detect the effects of SPARCL1 on the subcutaneous tumor formation and multi-organ metastasis of PTC cells in mice, as well as the inhibitory effect of recombinant SPARCL1 on tumors formed by PTC cells. The findings revealed that overexpression of the SPARCL1 gene, the secretory form of the SPARCL1 protein, and the recombinant SPARCL1 protein all significantly inhibited the malignant biological behaviors of PTC cells. Overexpression of SPARCL1 can inhibit the subcutaneous growth of tumor cells and their metastasis to the lungs, liver, and kidneys of mice, and recombinant SPARCL1 protein can also inhibit the growth of subcutaneous tumors. Mechanistically, SPARCL1 appears to mediate its anti-tumor effects through the SLC3A2-mediated ferroptosis pathway, suggesting a novel mechanism by which SPARCL1 influences PTC progression. In summary, SPARCL1 inhibits the proliferation, invasion, and metastasis of PTC, highlighting its potential as a candidate for innovative restorative therapies in PTC treatment.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984844","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":"Predictive model for the diagnosis of ectopic Cushing syndrome.","authors":"Wilfredo Antonio Rivera-Martínez, Carlos Esteban Builes-Montaño, Natalia Aristizábal Henao, Stefanía Cruz Calderón, Néstor Andrés Díaz Posada, María Johana Ramírez Castaño, Carlos Alfonso Builes Barrera, Claudia Marcela Gómez Serna, Alejandro Román-González, Alín Abreu Lomba, Andrés Felipe García Ramos, David Vernaza, Alfonso Soto Moreno, Ana Irigaray Echarri, María Dolores Ollero Garcia-Agullo, María Dolores Moure Rodríguez, Alejandro Pinzón-Tovar, Rogelio García-Centeno, Laura González Fernández, Andrés Cardona, Betina Biagetti, Fernando Guerrero-Pérez, Lucía Manzano Valero, Ana Castro Luna, Miguel Paja, Rosa Cámara, Johnayro Gutiérrez Restrepo, Pablo Alberto Castaño Ceballos, Néstor López Pompey, Pedro Iglesias, Victoria Alcazar, Edelmiro Menéndez Torre, Claudia Lozano Aida, Pol Candela, Felicia Alexandra Hanzu, Marta Araujo-Castro","doi":"10.1530/ERC-25-0348","DOIUrl":"10.1530/ERC-25-0348","url":null,"abstract":"<p><p>The purpose of our study was to develop and externally validate a multivariable diagnostic model to distinguish ectopic ACTH secretion (EAS) from Cushing's disease (CD) using routine clinical parameters. The model was derived from a Spanish multicenter retrospective cohort and externally validated in a Colombian cohort. Predictors were selected through a multivariable logistic regression model with penalized logistic regression (LASSO) using the Spanish cohort. Discriminative performance was assessed using the area under the ROC curve (AUC) and calibration using the slope, the origin, and the Brier score. The derivation cohort included 253 patients from Spain (199 with CD and 54 with EAS). The external validation cohort comprised 72 Colombian patients (53 with CD and 19 with EAS). In the derivation cohort, multivariable modeling identified four independent predictors: ACTH concentration, 24-h urinary free cortisol (UFC), serum potassium, and maximum pituitary tumor diameter. The final model demonstrated good discrimination in the derivation cohort (mean AUC of 0.987), with excellent calibration (calibration slope ranged from 0.998 to 5.22, intercept -0.2 to 0.99, Brier score 0.035). In external validation, model performance remained robust (AUC ranging from 0.9885 to 0.9890; Brier score 0.0381). The model achieved a sensitivity of 95.3%, specificity of 93.6%, positive predictive value of 82.3%, and negative predictive value of 98.7% for detecting EAS. Thus, the diagnostic model developed, based on routinely available clinical variables, shows high accuracy and calibration in differentiating between EAS and CD, supporting its potential use in diverse clinical settings and integration into diagnostic workflows.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}