Endocrine oncology (Bristol, England)最新文献

{"title":"Circulating biomarkers in the diagnosis and management of neuroendocrine neoplasms.","authors":"Angie S Xiang, Emma Boehm, Sunita M C De Sousa, Roderick J Clifton-Bligh, Richard W Tothill","doi":"10.1530/EO-25-0115","DOIUrl":"https://doi.org/10.1530/EO-25-0115","url":null,"abstract":"<p><p>Neuroendocrine neoplasms (NENs) comprise a broad family of tumours arising from the diffuse neuroendocrine system and endocrine glands, and vary widely in clinical behaviour ranging from indolent to highly aggressive. Established monoanalyte biomarkers including chromogranin A and NEN-derived hormones have clinical utility but some major limitations including non-specificity for tumour origin, variable sensitivity between NEN subtypes, inconsistent correlation with prognostic factors including metastasis, and can be falsely elevated in common non-NEN pathologies. The expansion of investigative NEN biomarkers through advancing omics technologies and computational methods holds potential to improve diagnosis, prognostication and aid therapy selection or trial allocation. This review will outline established and evolving NEN circulating biomarkers, and their roles in clinical practice.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186172","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":"Circulating Extracellular Matrix Biomarkers in the Detection of Carcinoid Heart Disease.","authors":"Tobias Stemann Lau, Elisavet Angeli, Riina Karoliina Oksjoki, Vibeke Guldbrand Rasmussen, Federica Genovese, Linda Skibsted Kornerup, Henning Grønbæk, Gitte Dam","doi":"10.1530/EO-26-0059","DOIUrl":"https://doi.org/10.1530/EO-26-0059","url":null,"abstract":"<p><strong>Objective: </strong>Carcinoid heart disease (CHD) is a severe fibrotic complication affecting cardiac valves in patients with neuroendocrine neoplasms (NEN). Early detection is crucial to improve prognosis. The value of the recommended screening biomarker, NT-proBNP, is uncertain. Biomarkers reflecting extracellular matrix (ECM) remodeling may capture early fibrogenesis. We aimed to evaluate circulating ECM biomarkers for detection of CHD and to compare their performance with NT-proBNP.</p><p><strong>Design and methods: </strong>In this cross-sectional study, we prospectively included patients with disseminated small intestinal NEN (siNEN). We performed transthoracic echocardiography (TTE) for CHD diagnosis, and blood samples were analyzed for 10 ECM biomarkers. Biomarker levels were compared between patients with and without CHD, and diagnostic performance was assessed using the area under the receiver operating characteristics (AUROC).</p><p><strong>Results: </strong>Among 98 patients, 16 (16%) had CHD. PRO-C3 levels were significantly elevated in patients with CHD compared with patients without CHD (median 19.3 ng/ml (IQR: 15.6-24.0) vs 14.3 ng/ml (IQR: 12.4-17.5), p = 0.002). The AUROC of PRO-C3 for CHD detection was 0.77 (95% CI: 0.64-0.90). At a cut-off level of 15.4 ng/ml, the sensitivity was 85 %, the specificity 56 %, the positive predictive value 27 %, and the negative predictive value 95 %. In the direct comparison between PRO-C3 and NT-proBNP, PRO-C3 did not outperform NT-proBNP (p = 0.09).</p><p><strong>Conclusion: </strong>PRO-C3, reflecting collagen type III formation, demonstrated good performance in CHD detection and may represent a complementary or potentially earlier marker than NT-proBNP. However, the performance of PRO-C3 was insufficient as a stand-alone tool, and further evaluation and exploration of new biomarkers in larger cohorts is required.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169293","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":"Geographic Variation in Diagnosis, Treatment, and Outcomes of Adrenocortical Carcinoma in the Americas: A Narrative Review.","authors":"Hugo Tanaka, George I Karadimov, María Laura Iglesias, Mariano Dioca, Luis Eduardo C Pinto, Sonir R Antonini, Maria C B V Fragoso, Jaydira Del Rivero","doi":"10.1530/EO-26-0043","DOIUrl":"https://doi.org/10.1530/EO-26-0043","url":null,"abstract":"<p><strong>Objective: </strong>Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy of the adrenal cortex. Given the heterogeneity of healthcare systems across the Americas, this review examines regional differences in access to diagnosis, treatment availability, and clinical outcomes, as well as their association with structural and socioeconomic factors.</p><p><strong>Design: </strong>Narrative literature review of observational studies and relevant regional evidence.</p><p><strong>Methods: </strong>PubMed, Scopus, and Web of Science were investigated for studies published between 2010 and 2025 reporting on diagnostic resources, treatment availability, clinical outcomes, or ACC-related population-specific genetic epidemiology across the Americas and the Caribbean. Due to substantial heterogeneity in study design, populations, and outcome measures, results were synthesized narratively and organized by geographic region and thematic domain.</p><p><strong>Results: </strong>Available evidence, particularly from the United States, indicates greater representation of high-volume referral centers, specialized multidisciplinary care, and structured diagnostic and treatment pathways. Conversely, reports from selected settings in Central and South America and the Caribbean describe limitations related to healthcare funding, fragmented care networks, and access to specialized therapies. These differences may be associated with diagnostic delays and reduced access to specialized treatment; however, the strength, depth, and comparability of the available evidence vary substantially across regions.</p><p><strong>Conclusions: </strong>Available evidence indicates regional variation in ACC diagnosis, treatment access, and reported outcomes across the Americas. Structural, socioeconomic, and geographic factors may contribute to these differences. Potential priorities include strengthening referral pathways, expanding specialized care, and supporting multidisciplinary management. More representative data are needed to enable robust regional comparisons and guide context-specific strategies.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139389","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":"Reproductive Function in Thyroid Cancer Survivors: A Gender-Based Perspective on Outcomes.","authors":"Rossella Mazzilli, Francesco Felicetti, Virginia Zamponi, Alice Nervo, Elisa Vaccaro, Giuseppe Defeudis, Emanuela Arvat, Antongiulio Faggiano","doi":"10.1530/EO-26-0047","DOIUrl":"https://doi.org/10.1530/EO-26-0047","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer is one of the most common endocrine malignancies, with an excellent long-term survival rate. As survivorship increases, attention has shifted toward chronic endocrine sequelae, including disturbances of gonadal function and fertility. Thyroid cancer therapies, including thyroidectomy, long-term thyroid-stimulating hormone (TSH) suppressive therapy, radioiodine (RAI), and targeted systemic treatments, may interfere with reproductive health through complex endocrine and gonadal mechanisms.</p><p><strong>Objective: </strong>This narrative review aims to examine the pathophysiological pathways linking thyroid cancer and its treatments to reproductive health in both men and women.</p><p><strong>Results: </strong>Thyroidectomy and chronic TSH suppression may alter sex steroid bioavailability and gonadotropin regulation through changes in thyroid hormone signalling and sex hormone binding globulin synthesis. RAI therapy exerts dose-dependent gonadotoxic effects, particularly affecting ovarian reserve and spermatogenesis, often in a transient and reversible manner, but potentially accelerating reproductive aging and damage. Targeted therapies may also contribute to reproductive dysfunction, through indirect systemic and endocrine mechanisms; however, data on thyroid cancer patients are still limited.</p><p><strong>Conclusions: </strong>Thyroid cancer related reproductive dysfunction may arise from the interaction of endocrine, and treatment related mechanisms. Although often subclinical, these alterations are biologically relevant and may influence long-term fertility potential. An accurate counselling for fertility management in thyroid cancer survivors appears relevant and highlights areas for future research.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139356","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":"Pituitary metastases: a real-world single-center surgical cohort.","authors":"Luigi Demarchis, Sabrina Chiloiro, Antonella Giampietro, Marco Gessi, Ciro Mazzarella, Silvia Chiesa, Rosalinda Calandrelli, Pier Paolo Mattogno, Simona Gaudino, Laura De Marinis, Liverana Lauretti, Quintino Giorgio D'Alessandris, Guido Rindi, Francesco Doglietto, Antonio Bianchi, Alfredo Pontecorvi","doi":"10.1530/EO-26-0092","DOIUrl":"https://doi.org/10.1530/EO-26-0092","url":null,"abstract":"<p><strong>Background: </strong>The pituitary is a rare site for metastatic spread. Pituitary metastases (PMs) account for about 1% of lesions removed by pituitary surgery. Data on epidemiology, symptoms, pituitary hormone assessment, and radiological findings are limited. This paper aimed to describe our retrospective cohort of histologically diagnosed PMs.</p><p><strong>Methods: </strong>A single-center, retrospective, observational cohort study was conducted on patients diagnosed with PM who underwent surgical resection between 2000 to 2025. We analyzed epidemiological, clinical, radiological, and surgical data about these lesions.</p><p><strong>Results: </strong>Nineteen PMs were identified (9 males and 10 females). The mean age at diagnosis of PMs was 57.8 years. Most patients presented with symptoms at the first clinical evaluation, and the most frequent onset symptom was neuro-ophthalmological disorders (84.2%). Pituitary hormonal deficiencies were diagnosed in 12 patients: three patients were affected by pan-hypopituitarism (16.7%), one patient (5.5%) by anterior partial hypopituitarism, 6 patients with only an ACTH deficiency. AVD was diagnosed in 7 patients (36.8%). In 21% of patients, the pituitary gland was identified as the first site of metastasis of the primary neoplasm. Fourteen patients out of the 16 with available data (87.5%) carried residual/recurrent disease after surgery. The most frequently found neoplasms were lung cancer and breast cancer. Five patients underwent radiotherapy after surgery. Median overall survival from surgery was 23.5 months.</p><p><strong>Conclusion: </strong>PMs had an increasing incidence in recent years and should be considered in the etiological diagnosis of pituitary hormonal deficiencies and/or signs due to the impairment of anatomical structures of the sella turcica.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119485","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":"Functioning pancreatic neuroendocrine neoplasms: Diagnosis and current treatment.","authors":"Panagiota Konstantakou, Ariadni Spyroglou, Marina Tsoli, Anna Angelousi, Gregory Kaltsas, Krystallenia I Alexandraki","doi":"10.1530/EO-26-0005","DOIUrl":"https://doi.org/10.1530/EO-26-0005","url":null,"abstract":"<p><p>Pancreatic functioning neuroendocrine neoplasms (PanNENs) are rare and characterized by variable and heterogeneous clinical manifestations, comprising both symptoms and signs of tumor growth and systemic manifestations of hormonal hypersecretion. The diagnosis is challenging due to their rarity, neoplasm localization and diverse secretory profile. A subset of these neoplasms may develop in the context of inherited syndromes and harbor specific genetic alterations requiring genetic counseling of other family members. These particular features make the management of patients with a functioning PanNEN syndrome requiring a multidisciplinary approach. Surgical resection of local disease, antisecretory medical treatment, locoregional treatment and systemic treatments are employed on an individualized basis. The treatment landscape of advanced NENs progressing after systemic treatment or after exhibiting intolerance to sequential lines of treatment is rapidly evolving supporting the introduction of additional therapies with promising results.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066480","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":"Current evidence across the treatment spectrum of adrenocortical carcinoma: a comprehensive scoping review.","authors":"Angélica María González-Clavijo, Luis F Fierro-Maya, Diego F Ballen, Deyanira González-Devia, Andrés Arturo Cuéllar-Cuéllar, Mauricio García-Mora, Diego M González-Ramírez, Mireya Tapiero-García, Alejandro Román-González, Marino Cabrera, Jesús O Sánchez-Castillo, Sara Correa-Giraldo, Carlos E Builes-Montaño","doi":"10.1530/EO-26-0079","DOIUrl":"10.1530/EO-26-0079","url":null,"abstract":"<p><p>Adrenocortical carcinoma is a rare and aggressive malignancy for which high-quality evidence to guide clinical decision-making remains limited. This scoping review aimed to map and synthesize the extent, nature, and direction of evidence across five therapeutic domains in the management of adrenocortical carcinoma. Following the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidance, MEDLINE, Embase, and the Cochrane Library were searched without date restrictions. Eligible sources included clinical trials, observational studies, systematic reviews, and clinical guidelines addressing any treatment modality for adrenocortical carcinoma. Data were extracted using a standardized form and synthesized narratively across domains. Evidence visualizations and an intervention-by-domain matrix were developed to identify areas of consistency, uncertainty, and research gaps. Forty-nine studies met the inclusion criteria. Complete tumor resection with negative margins consistently emerged as the strongest prognostic factor. Minimally invasive adrenalectomy showed comparable outcomes only in carefully selected low-risk patients. Adjuvant mitotane demonstrated potential benefit in high-risk disease but not in low- to intermediate-risk patients. In metastatic disease, multimodal management incorporating etoposide, doxorubicin, cisplatin, and mitotane, together with metastasectomy and local therapies, was associated with improved outcomes in selected cases. Recurrence was frequent and often occurred early, particularly in large or invasive tumors. Cortisol-secreting tumors were associated with higher postoperative morbidity and earlier recurrence. Although the available evidence is predominantly retrospective and heterogeneous, consistent patterns emerge that can inform clinical management. This review provides a structured evidence base for future consensus development and highlights priorities for further research.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260079"},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066498","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>AGK::BRAF</i> fusion activates MAPK signaling, promotes genomic instability, and reduces NIS expression in thyroid cancer cells.","authors":"Luiza Sisdelli, Welbert Gomes Rocha, Débora Mota Dias Thomaz, Roxane Hatanaka, Renata Elen Costa da Silva, Guilherme Henrique, Caroline Serrano-Nascimento, Matheus Fabião, Aline Rangel-Pozzo, Sabine Mai, Janete Maria Cerutti","doi":"10.1530/EO-25-0096","DOIUrl":"10.1530/EO-25-0096","url":null,"abstract":"<p><p>The <i>AGK::BRAF</i> fusion is a recurrent oncogenic alteration in sporadic pediatric papillary thyroid carcinoma (PTC), frequently associated with multifocal disease and pulmonary metastasis. However, the molecular and cellular consequences of <i>AGK::BRAF</i> expression in thyroid follicular cells remain poorly defined. Here, we investigated the biological effects of <i>AGK::BRAF</i> in PCCL3 thyroid cells and compared them with those induced by clinically established pediatric PTC oncogenic drivers, including <i>RET/PTC1</i>, <i>RET/PTC3</i>, <i>ETV6::NTRK3</i>, <i>BRAF V600E</i>, and wild-type <i>BRAF</i>. <i>AGK::BRAF</i>-expressing cells exhibited the most robust MAPK/ERK activation, characterized by markedly enhanced ERK and MEK phosphorylation relative to all other oncogenic drivers analyzed. By contrast, STAT3 and AKT signaling remained comparatively modest and did not show consistent oncogene-specific activation patterns. Functionally, <i>AGK::BRAF</i> expression induced features of thyroid dedifferentiation, including reduced sodium-iodide symporter (NIS) expression and impaired iodide uptake. Concomitantly, <i>AGK::BRAF</i>-expressing cells exhibited increased frequencies of micronuclei and chromatin bridges, together with disruption of three-dimensional telomere architecture, including reduced telomere signal number and intensity, altered spatial organization, and increased nuclear volume. Three-dimensional structured illumination microscopy (3D-SIM) further demonstrated chromatin remodeling, characterized by increased chromatin condensation accompanied by enlarged interchromatin spaces. Collectively, these findings suggest that <i>AGK::BRAF</i> is a dominant oncogenic driver of sustained MAPK/ERK signaling coupled to thyroid dedifferentiation, nuclear architectural remodeling, telomere dysfunction, and genomic instability. These coordinated molecular and structural alterations provide a mechanistic basis for the aggressive clinical course observed in <i>AGK::BRAF</i>-driven pediatric PTC.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e250096"},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066547","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":"Clinical application of digital pathology in small intestinal neuroendocrine tumours: proposal of a new G0 category.","authors":"Nathalie Guedj, Guillaume Cléry, Anaïs Chassac, Nathalie Colnot, Vinciane Rebours, Jérôme Cros, Louis de Mestier, Anne Couvelard, Matthieu Tihy","doi":"10.1530/EO-26-0061","DOIUrl":"10.1530/EO-26-0061","url":null,"abstract":"<p><strong>Introduction: </strong>Small intestinal neuroendocrine tumours (siNETs) are usually indolent neoplasms, most of which are classified as grade 1 with very low proliferative activity. In practice, Ki-67 in G1 siNETs is often reported simply as '<3%', limiting prognostic discrimination. Digital pathology now enables reliable automated quantification of very low Ki-67 values. We investigated whether precise Ki-67 quantification could improve prognostic stratification in G1 siNETs.</p><p><strong>Methods: </strong>We retrospectively included 63 consecutive patients who underwent surgery for a G1 siNET at Beaujon Hospital between 2001 and 2017. Ki-67 was quantified on primary tumours (PTs) and, when available, lymph node and liver metastases, using QuPath automated image analysis. Ki-67 was assessed in the highest-proliferation hotspot (0.4 mm²; >2,000 tumour cells; Ki-67_max) and as the mean of five hotspots (Ki-67_mean). The primary endpoint was recurrence-free survival (RFS).</p><p><strong>Results: </strong>Among 63 patients, 33 underwent curative-intent surgery (median age: 56 years; 69% male). Median tumour size was 20 mm. At surgery, 87% were node-positive and 67% had synchronous metastases. Median Ki-67_max/Ki-67_mean in PTs was 0.99%/0.71%. In localised disease, Ki-67_max predicted RFS (AUROC = 0.84). Median follow-up was 60.2 months. Median RFS was 112 months in patients with Ki-67_max ≥1%, whereas no recurrences occurred in those with Ki-67_max <1% (<i>P</i> = 0.04). Ki-67_mean provided no additional prognostic value.</p><p><strong>Conclusion: </strong>Precise digital Ki-67 quantification refines prognostic stratification in G1 siNETs. Tumours with Ki-67 <1% may represent a biologically distinct 'G0' subgroup associated with extremely low recurrence risk after curative surgery.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260061"},"PeriodicalIF":0.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149066460","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":"Tumor risks and surveillance outcomes in <i>SDHA</i> variant carriers.","authors":"Kelsey Ellis, Daniel Christensen, Jacob Beiringer, Anne Naumer, Jennie Vagher, Richard Wiggins, Hilary McCrary, Luke Buchmann","doi":"10.1530/EO-26-0048","DOIUrl":"10.1530/EO-26-0048","url":null,"abstract":"<p><strong>Objective: </strong><i>SDHA</i> germline pathogenic variants confer a lower paraganglioma risk compared with other hereditary paraganglioma genes. Reduced screening for carriers without a personal or family history of <i>SDHA</i>-associated tumors has been proposed; however, supporting data remain limited. This single-institution cohort study addresses this by characterizing <i>SDHA</i> carrier tumor features and long-term screening outcomes.</p><p><strong>Design: </strong>This is a retrospective cohort study with longitudinal surveillance follow-up.</p><p><strong>Methods: </strong>Clinical records of patients with an <i>SDHA</i> likely pathogenic or pathogenic germline variant identified between July 2015 and July 2025 in the Family Cancer Assessment Clinic at the University of Utah Huntsman Cancer Institute were reviewed.</p><p><strong>Results: </strong>Among 106 <i>SDHA</i> carriers, 15% had a personal history of an <i>SDHA</i>-associated tumor. Of identified tumors, 47% were metastatic or demonstrated malignant behavior (3/3 extra-adrenal PPGLs, 4/5 GISTs, 0/7 head/neck PPGLs). No affected carriers had known family history of <i>SDHA</i>-associated tumors, and no cases of multiple related tumors were observed. Most carriers (63%) lacked a personal or family history of <i>SDHA</i>-associated tumors. Over 10 years of high-risk screening, zero previously unidentified <i>SDHA</i>-associated tumors were found.</p><p><strong>Conclusion: </strong>Our findings align with prior evidence that <i>SDHA</i> variants confer a lower tumor risk than other hereditary PPGL genes, lending support to an <i>SDHA</i>-specific screening approach. However, higher rates of malignant tumor behavior in affected carriers compared with sporadic disease suggest <i>SDHA</i> variants may be impactful in contexts like treatment decision-making. These contrasts highlight that while modifying or forgoing tumor screening may be reasonable for many carriers, a nuanced clinical approach remains essential for this population.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"6 1","pages":"e260048"},"PeriodicalIF":0.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009506","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}