Endocrine oncology (Bristol, England)最新文献

{"title":"Differential expression of POMC-processing genes in corticotroph tumors.","authors":"Elisa Lamback, Renan L Miranda, Laryssa Mendonça, Camila S de Figueiredo, Kaio C R Salum, Rômulo S Dezonne, Luiz Eduardo Wildemberg, Mônica R Gadelha","doi":"10.1530/EO-26-0003","DOIUrl":"https://doi.org/10.1530/EO-26-0003","url":null,"abstract":"<p><strong>Objective: </strong>Corticotroph tumors (CTs) derive from the <i>TBX19</i> lineage and are functioning (FCTs) or nonfunctioning (NFCTs). In FCTs, the main pathogenic variants are found in <i>USP8,</i> enhancing proopiomelanocortin (<i>POMC</i>) transcription through epidermal growth factor receptor (EGFR) signaling, resulting in a higher secretion index compared with wild type (WT). POMC is cleaved by prohormone convertase 1/3, encoded by proprotein convertase subtilisin/kexin type 1 gene (<i>PCSK1</i>), into ACTH. <i>PCSK1</i> is inhibited by <i>PCSK1N,</i> which in turn is inhibited by transcription factor paired box 6 (<i>PAX6</i>). We aimed to compare gene expressions involved in POMC processing among NFCTs, <i>USP8</i>+ FCTs, and WT FCTs.</p><p><strong>Methods: </strong>Fresh CTs were collected to quantify <i>TBX19</i>, <i>POMC</i>, <i>EGFR</i>, <i>PCSK1</i>, <i>PCSK1N,</i> and <i>PAX6</i> by polymerase chain reaction. Sanger sequencing was performed to detect <i>USP8</i> variants. ACTH levels were normalized to tumor diameter to calculate the secretion index.</p><p><strong>Results: </strong>We included 42 NFCTs, 13 WT FCTs, and 11 <i>USP8</i>+ FCTs. NFCTs had lower <i>TBX19</i>, <i>POMC</i>, and <i>PAX6</i> compared with both FCT groups, but similar <i>PCSK1N</i>. <i>TBX19</i> correlated positively with <i>POMC</i> (<i>R</i> = +0.460; <i>P</i> = 0.002) and <i>PAX6</i> (<i>R</i> = +0.327; <i>P</i> = 0.030). <i>USP8+</i> FCTs had a higher secretion index (<i>P</i> = 0.019), higher <i>PCSK1</i> (<i>P</i> = 0.037), and also lower <i>PCSK1N</i> (<i>P</i> = 0.041), compared with WT, despite similar <i>TBX19</i> and <i>POMC</i>. Secretion index only correlated with <i>PCSK1N</i> (<i>R</i> = -0.469; <i>P</i> = 0.021).</p><p><strong>Conclusions: </strong>In NFCTs, low <i>TBX19</i> may contribute to their nonfunctioning phenotype. In FCTs, <i>USP8</i>+ and WT displayed similar <i>POMC</i> levels, but downstream <i>POMC</i>, <i>USP8</i>+ had a higher <i>PCSK1</i> and lower <i>PCSK1N</i>, which may account for their comparatively increased secretory activity.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260003"},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824097","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":"Evaluating the clinical utility of iodine-123 scans in follow-up for differentiated thyroid cancer: a single-centre study.","authors":"Robert Smith-Baker, Richard Meades, Arunansu Kar","doi":"10.1530/EO-25-0105","DOIUrl":"https://doi.org/10.1530/EO-25-0105","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the impact of iodine-123 (I-123) diagnostic scintigraphy on management outcomes in patients undergoing follow-up for differentiated thyroid carcinoma (DTC), and to assess whether multidisciplinary team (MDT) discussion influences subsequent clinical pathways.</p><p><strong>Methods: </strong>A retrospective analysis was conducted of patients with DTC who underwent I-123 scintigraphy at an NHS trust. Demographic data, scan findings, and subsequent clinical actions were collected. Scans were categorised as MDT endorsed or requested by individual clinicians. Outcomes were assessed by distinguishing initial diagnostic actions prompted by I-123 imaging from definitive management outcomes following completion of downstream investigations.</p><p><strong>Results: </strong>A total of 55 I-123 scans from 51 patients were included. New or abnormal findings were identified in 21 scans (38.2%). Initial diagnostic actions followed 23 scans (41.8%), most commonly further imaging. When management outcomes were reassessed after completion of downstream investigations, no definitive change in management occurred in 40 scans (72.7%), while 13 scans (23.6%) resulted in a definitive management change; in 2 scans (3.6%), outcomes were unclear. MDT-endorsed scans more frequently prompted initial diagnostic actions, although this difference was not statistically significant. Outcomes for MDT-requested scans and individually requested scans were near-identical (definitive change in management in 20% vs 20.7).</p><p><strong>Conclusions: </strong>I-123 scintigraphy can influence clinical decision-making during follow-up of patients with differentiated thyroid cancer, most commonly by prompting further diagnostic investigation. However, definitive changes in management occur in a minority of cases. These findings support a selective rather than routine role for I-123 imaging in follow-up.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250105"},"PeriodicalIF":0.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13087875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724922","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":"Therapy-related myeloid neoplasms following peptide receptor radionuclide therapy for neuroendocrine neoplasms: case series reporting characteristics and outcomes from single-centre experience.","authors":"Wallace Chow, Ivy Wen, Claire Mok, Kathryn Huang, William Stevenson, Paul J Roach, Dale L Bailey, Connie I Diakos, Stephen J Clarke, Nick Pavlakis, David L Chan","doi":"10.1530/EO-25-0107","DOIUrl":"https://doi.org/10.1530/EO-25-0107","url":null,"abstract":"<p><strong>Objective: </strong>Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTATATE is increasingly used in the treatment of metastatic neuroendocrine neoplasms (NENs). Marrow toxicity resulting in therapy-related myeloid neoplasms (t-MNs) remains a rare but fatal complication of PRRT, with a limited understanding of prognostic or predictive factors.</p><p><strong>Methods: </strong>We conducted a single-centre retrospective review of all patients with metastatic NEN who received at least one cycle of PRRT and subsequently developed t-MN confirmed on bone marrow biopsy.</p><p><strong>Results: </strong>Thirteen out of 306 patients (4.2%) developed t-MN during follow-up, confirmed on bone marrow biopsy. The median time from cycle 1 of PRRT to diagnosis of t-MN was 48.3 months (range: 5.4-110.1 months). The median number of PRRT cycles was 4 (range: 3-8). Nine (69%) patients received concomitant radiosensitising chemotherapy with capecitabine, and one (7.7%) had the combination of capecitabine and temozolomide. The median overall survival from cycle 1 of PRRT was 61.9 months (range: 18.5-112.2 months). The median overall survival from diagnosis of t-MN was 10.4 months (range: 1.9-89.3 months). An unfavourable karyotype, a higher degree of cytopaenia and a higher blast percentage in bone marrow were associated with worse survival outcomes of t-MN.</p><p><strong>Conclusions: </strong>t-MN following PRRT is an uncommon but serious complication that can occur several years after treatment. This case series highlights the poor prognosis following t-MN diagnosis, particularly if untreated. PRRT is an effective treatment modality for NEN, but prospective studies are needed to explore factors predictive of t-MN development.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250107"},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635352","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 clinical impact of androgens in endometrial cancer: cancer promoter or suppressor?","authors":"Xirong Wu, Wenyan Tian, Yingmei Wang","doi":"10.1530/EO-25-0040","DOIUrl":"https://doi.org/10.1530/EO-25-0040","url":null,"abstract":"<p><strong>Purpose: </strong>Androgens are associated with the risk of endometrial carcinoma (EC). However, their roles as prognostic factors are less clear. This study aims to investigate the prognostic impact of different androgens.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of patients who had previous endometrial sampling that showed EC between August 19, 2003, and November 4, 2015. This study included 465 patients with an average follow-up of 37 months. We examined associations between endogenous testosterone levels (total, bioavailable and free testosterone) and the clinical outcomes in patients with EC. Serum levels of bioavailable testosterone were calculated using the total testosterone level and the sex hormone-binding globulin concentration (measured by chemiluminescent and radioimmunoassays, respectively).</p><p><strong>Results: </strong>Higher circulating concentrations of total and bioavailable testosterone were associated with a higher risk of type I endometrial cancer (OR = 1.015, 95% CI: 1.008-1.022; OR = 1.395, 95% CI: 1.266-1.536, respectively), but the similar association was not found in type II patients (OR = 1.009, 95% CI: 0.998-1.020; OR = 1.208, 95% CI: 0.998-1.461, respectively). However, higher levels of testosterone in EC patients correlated with favorable clinicopathological features, especially bioavailable and free testosterone. Furthermore, Kaplan-Meier survival analysis indicated that elevated bioavailable and free testosterone levels were associated a longer overall survival (<i>P</i> = 0.048, <i>P</i> = 0.036, respectively), but this trend was not statistically significant after adjustment for other prognostic factors (<i>P</i> = 0.312, <i>P</i> = 0.272, respectively).</p><p><strong>Conclusion: </strong>Elevated serum testosterone levels were associated with an increased risk of type I cancers. Although androgens showed certain prognostic values, they were not independent prognostic factors. Different androgenic indexes showed different clinical implications. The risk estimates could refer to total and/or bioavailable testosterone. Bioavailable and/or free indexes may be better markers for the probable prognostic effects.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250040"},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596448","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":"Mesenteric paraganglioma mimicking nodal metastasis of an occult small intestinal neuroendocrine tumor.","authors":"Anna Battistella, Marco Schiavo Lena, Valentina Andreasi, Stefano Partelli, Massimo Falconi","doi":"10.1530/EO-25-0117","DOIUrl":"10.1530/EO-25-0117","url":null,"abstract":"<p><p>Paragangliomas (PGLs) are rare neuroendocrine neoplasms of neural-crest origin, with primary mesenteric localization representing an exceptionally uncommon entity that is rarely considered in the preoperative differential diagnosis of mesenteric masses. We report the case of a 51-year-old woman who was referred to our institute following the incidental detection of a 12 × 9 mm hypervascular nodule within the pelvic small bowel mesentery on contrast-enhanced computed tomography (CT). Subsequent ⁶⁸Ga-DOTATOC positron emission tomography/CT showed intense somatostatin receptor uptake confined to the mesenteric nodule, with no other lesions. Dedicated pan-colonoscopy was unremarkable and 24-h urinary 5-hydroxyindoleacetic acid was within normal limits. Preoperative diagnosis of nodal metastasis from an occult ileal neuroendocrine tumor was made, and laparoscopic surgery was undertaken. Meticulous bimanual palpation of the small bowel with transillumination did not reveal any primary lesions, while a 1 cm mesenteric mass was identified and excised. Histology revealed a solid tumor with Zellballen architecture with tumor cells positive for chromogranin A and GATA3, and negative stains for cytokeratin, CDX2, and serotonin, establishing the diagnosis of paraganglioma. This case highlights the importance of recognizing paraganglioma as a potential diagnostic mimic in solitary somatostatin receptor-avid mesenteric nodules to prevent unnecessary investigations and guide appropriate surgical management.</p><p><strong>Learning points: </strong>Primary mesenteric paragangliomas should be considered in the differential diagnosis of solitary, hypervascularized mesenteric masses.A solitary SSTR-avid mesenteric nodule in an asymptomatic, biochemically silent patient does not necessarily imply nodal metastasis from an occult small intestinal neuroendocrine tumor.Considering alternative diagnoses may avoid unnecessary endoscopic, radiological, and surgical investigations for an intestinal primary lesion.Definitive diagnosis and risk stratification rely on histopathology and immunohistochemistry, including epithelial markers, GATA3, and SDHB.Awareness of mesenteric paraganglioma as a diagnostic mimic can prevent overtreatment and guide appropriate surgical management.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250117"},"PeriodicalIF":0.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596405","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":"Vitamin D receptor expression in germinal centre type diffuse large B-cell lymphoma cells is associated with vitamin D insensitivity.","authors":"Elizabeth J Soilleux, Amanda Anderson, Emma Roberts, Linden Lyne, Kah Keng Wong, Hayley Spearman, Stefano Casola, Alison H Banham, Duncan M Gascoyne","doi":"10.1530/EO-25-0057","DOIUrl":"10.1530/EO-25-0057","url":null,"abstract":"<p><strong>Objective: </strong>Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of non-Hodgkin lymphomas (NHLs) often sub-classified into major germinal centre (GC) and activated B-cell (ABC) cell-of-origin types. We have previously shown vitamin D receptor (VDR) expression in plasmablastic ABC-DLBCL cells and demonstrated inhibition of their growth by exogenous vitamin D (VitD3); however, the vitamin D biology of GC-DLBCL cells remained unclear.</p><p><strong>Design/methods: </strong>Study of VDR and related molecule expression and vitamin D response across a panel of DLBCL and myeloma cell lines by western blot, qPCR, flow cytometry and cell counting techniques. Analysis of gene expression and ChIP-seq in published cell line and/or primary DLBCL datasets.</p><p><strong>Results: </strong>We show that some BCL6^hi GC-DLBCL cell lines express low levels of VDR, but appear resistant to VitD3, and associate VDR positivity in both GC- and ABC-DLBCL cell lines with the poor prognosis plasmacytic/activation marker CD38. ChIP-seq data suggest that <i>VDR</i> may be a direct BCL6 target. Functionally, VitD3 and the EB-1089 analogue can reduce growth, inhibit MYC expression and increase CD38 expression by 50-400% on ABC-DLBCL and myeloma but not GC-DLBCL cells. <i>CD38</i> is also activated by VitD3 treatment of human peripheral B cell lines, where VDR can bind to the <i>CD38</i> locus, suggesting direct regulation.</p><p><strong>Conclusions: </strong>Combined VDR and cell-of-origin assessment may contribute to a greater understanding of vitamin D's role in mature B-cell lymphoma and its interplay with BCL6 and MYC.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250057"},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517298","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":"MRI and ¹⁸F-fluorothymidine PET-MR for the early evaluation of renal and bone marrow effects in ¹⁷⁷Lu-DOTATATE therapy.","authors":"Angeliki Dimopoulou Creusen, Edvin Johansson, Per Hagmar, Håkan Ahlström, Dan Granberg","doi":"10.1530/EO-25-0036","DOIUrl":"https://doi.org/10.1530/EO-25-0036","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate whether early renal and bone marrow effects - previously identified through laboratory tests - can be detected using MRI and ¹⁸F-FLT PET-MR in neuroendocrine tumor patients treated with ¹⁷⁷Lu-DOTATATE. Despite known early changes, precise clinical tools to monitor these effects remain limited.</p><p><strong>Methods: </strong>Ten patients with metastatic NETs, scheduled to initiate at least four treatment cycles of ¹⁷⁷Lu-DOTATATE, were included. MRI was performed at all designated treatment time points, whereas F-FLT PET was acquired only at baseline and on day 2 following treatment initiation. Bone marrow (BM) fat conversion, proliferative activity, and renal effects were studied with MRI and ¹⁸F-FLT PET-MR. Laboratory tests for hematology and kidney and liver function were taken.</p><p><strong>Results: </strong>Six patients completed the full imaging protocol with MRI, of whom ¹⁸F-FLT PET-MR examinations were performed in two patients. All subjects demonstrated increased BM fat content during the study interval, with a mean of +12.8%. The magnitude of the increase varied substantially, from +3.8% to +23.5%. There was a strong correlation between increased BM fat content and reduced peripheral blood cell counts. Decreased FLT uptake was found on day 2 after treatment. An increase in renal arterial flow and parenchymal volume was detected during the first week after treatment. No sustained renal effects were observed.</p><p><strong>Conclusions: </strong>The hematological effects observed with laboratory tests after ¹⁷⁷Lu-DOTATATE treatment in neuroendocrine tumor patients can be detected by MRI as an increase in bone marrow fat content. This finding was supported by decreased FLT uptake on ¹⁸F-FLT PET-MR, indicating decreased bone marrow cell proliferation. MRI can also identify renal effects associated with this therapy.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250036"},"PeriodicalIF":0.0,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446139","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":"Physical activity and systemic treatment outcomes in advanced thyroid cancer.","authors":"Carla Colombo, Daniele Ceruti, Fabrizio Cervellini, Massimiliano Succi, Simone De Leo, Matteo Trevisan, Claudia Moneta, Marina Lugaresi, Gianlorenzo Dionigi, Giacomo Gazzano, Luca Persani, Laura Fugazzola","doi":"10.1530/EO-25-0095","DOIUrl":"https://doi.org/10.1530/EO-25-0095","url":null,"abstract":"<p><strong>Introduction: </strong>Physical activity interventions could play a critical role in tolerance and outcome during anti-neoplastic therapy.</p><p><strong>Aim: </strong>This study aims to evaluate the role of physical activity and its maintenance on treatment safety and efficacy in patients with advanced thyroid cancer.</p><p><strong>Methods: </strong>We enrolled 28 patients with advanced thyroid cancer, treated with kinase inhibitor therapy for a median follow-up of 26 months. Three modified long-form International Physical Activity Questionnaires were administered before treatment, at an intermediate follow-up point and at the last follow-up point. Metabolic equivalents were calculated at each time point. Tumour response was evaluated according to RECIST, version 1.1.</p><p><strong>Results: </strong>Patients inactive at baseline experienced more treatment interruptions during both the first (85 vs 30%, <i>P</i> = 0.01) and second half of the follow-up period (85 vs 47%, <i>P</i> = 0.08) and had more frequently a progressive disease (42 vs 14%, <i>P</i> = 0.15), compared to those who were mildly or highly active. Patients who declined their physical activity during treatment had more treatment interruptions (100 vs 31%, <i>P</i> = 0.006), more adverse events considering both the number (>5) and the grade (≥3) (100 vs 31%, <i>P</i> = 0.006 and 100 vs 38%, <i>P</i> = 0.01), more hospitalization due to toxicities (66 vs 8%, <i>P</i> = 0.008) and a more progressive disease (40 vs 8%, <i>P</i> = 0.09). The number of toxicities was inversely correlated with metabolic equivalents lost (<i>r</i> = -0.15, <i>P</i> = 0.04).</p><p><strong>Conclusion: </strong>This is the first study showing that maintaining adequate physical activity levels is associated with better treatment tolerance and outcomes in advanced thyroid cancer patients on kinase inhibitor therapy, supporting the need for prospective prehabilitation trials.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250095"},"PeriodicalIF":0.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12974739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437987","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":"Multimodal management of hormonal and oncological progression in PTHrP-secreting pancreatic neuroendocrine tumours.","authors":"Alexandra Zueva, Ee Wen Loh, Shamiso Masuka, Jonathan Wadsley, John Newell-Price, Alia Munir","doi":"10.1530/EO-25-0085","DOIUrl":"https://doi.org/10.1530/EO-25-0085","url":null,"abstract":"<p><strong>Summary: </strong>Parathyroid hormone-related peptide (PTHrP)-secreting pancreatic neuroendocrine tumours (Pan-NETs) are a rare cause of humoural hypercalcaemia of malignancy (HCM). We report two contrasting cases of metastatic well-differentiated PTHrP-secreting Pan-NETs (WHO grade 2; Ki-67: 7 and 8%, respectively), highlighting the variability in disease progression, response to multiple treatment modalities, and long-term outcomes. The first patient, a 55-year-old woman with mild hypercalcaemia who was largely asymptomatic except for a persistent dry cough at presentation, achieved stable disease control following eight years of treatment with somatostatin analogues (SSAs), peptide receptor radionuclide therapy (PRRT), and chemotherapy. During a prolonged period of uncontrolled hypercalcaemia prior to chemotherapy, she developed rapid bilateral hip osteoarthrosis and tumour calcification, a rare complication from long-standing calcium elevation. The second patient, a 34-year-old woman, had a more aggressive disease course, requiring multiple hospital admissions for refractory moderate-to-severe hypercalcaemia and variceal bleeding. Despite initial tumour stabilisation following PRRT, she developed refractory hypercalcaemia, demonstrating only partial response to zoledronate, high-dose denosumab, and maximal somatostatin analogue therapy, and ultimately succumbed to progressive disease and metabolic deterioration. These cases underscore the heterogeneity of PTHrP-secreting Pan-NETs and the challenges in optimising treatment strategies, given the lack of data on the optimal sequencing of therapies. Notably, calcium can serve as a reliable tumour marker for disease control, with persistent severe hypercalcaemia being a potential prognostic factor of poor outcome in patients with PTHrP-related hypercalcaemia. International collaboration and knowledge exchange are needed to ascertain the most effective management of this rare functional syndrome.</p><p><strong>Learning points: </strong>Consider PTHrP secretion in the context of hypercalcaemia in Pan-NETs.Calcium level can serve as a tumour marker in patients with PTHrP-related hypercalcaemia for assessing treatment response, disease progression, and tumour aggressiveness, with persistent hypercalcaemia being a prognostic factor for poor outcome.Hypercalcaemia may be resistant to standard treatments, and higher doses of denosumab may be necessary to achieve adequate control.An individualised multimodal treatment approach, including SSAs, PRRT, targeted therapy, chemotherapy, or a combination thereof, should be utilised to control PTHrP-secreting Pan-NETs.Although the optimal sequencing of these therapies remains unclear, multidisciplinary team discussions and shared decision-making are essential in managing such complex cases.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250085"},"PeriodicalIF":0.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215070","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":"Primary tumor size as a prognostic factor in duodenal neuroendocrine neoplasms ≤20 mm: a population-based SEER analysis.","authors":"Giuseppe Lamberti, Francesco Panzuto, Maria Rinzivillo, Flaminia Benedetta Zoboli, Irene Zannini, Elisa Andrini, Elisabetta Dell'Unto, Riccardo Di Pangrazio, Davide Campana","doi":"10.1530/EO-25-0108","DOIUrl":"10.1530/EO-25-0108","url":null,"abstract":"<p><strong>Objective: </strong>The prognostic value of primary tumor size in duodenal neuroendocrine neoplasms (dNENs) ≤20 mm remains uncertain. Although size is used to guide management, its independent effect on survival is unclear.</p><p><strong>Design and methods: </strong>We performed a population-based study using the US SEER database (1975-2021), including adults with histologically confirmed dNENs ≤20 mm. Disease-specific survival (DSS) was the primary endpoint. Associations between tumor size, stage, lymph-node involvement, and DSS were evaluated using chi-squared tests, logistic regression, Kaplan-Meier curves, and Cox models. Receiver operating characteristic (ROC) analysis identified the optimal size cutoff. Mediation analysis assessed whether stage or grade mediated the size-DSS relationship.</p><p><strong>Results: </strong>Among 3,515 eligible cases, median age was 65 years, 51% were male, and 89% had well-differentiated NETs. Most tumors were localized (85.2%) and ≤10 mm (74.4%). Median follow-up was 56 months, with 160 disease-specific deaths (4.6%). In univariable analysis, size >10 mm was associated with worse DSS, but the association disappeared after adjustment for grade, stage, and surgery. Grade G3 and advanced stage independently predicted poorer survival, while radical surgery was protective. Larger tumors were more frequently high grade and advanced stage (<i>P</i> < 0.001), and each 1 mm increase raised the odds of nodal metastasis by 12% (OR 1.12). ROC analysis identified a size threshold of 10.5 mm (AUC = 0.74). Stage mediated only ∼2% of the size-DSS association.</p><p><strong>Conclusions: </strong>In duodenal NENs ≤ 20 mm, tumor size >10 mm correlates with disease extent but does not independently affect DSS, supporting its role as a stratification marker rather than a prognostic factor.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250108"},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204056","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}