Endocrine oncology (Bristol, England)最新文献

{"title":"NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.","authors":"Po Hien Ear, Ilaria Marinoni, Talya Dayton, Rachael Guenter, Dawn E Quelle, Anna Battistella, Floryne O Buishand, Suganthi Chittaranjan, Yi-Cheih Nancy Du, Ines Marques, Natalia S Pellegata, Samira M Sadowski, Amit Tirosh, Simon April-Monn, Cinzia Aurilia, Renata Jaskula-Sztul, Maria Jesús Baena Moreno, Simone Donati, Katherine A English, Maria Almudena Hernandez Llorens, Harry Hodgetts, Francesca Marini, Maria Martins, Gaia Palmini, Beatriz Soldevilla, Jörg Schrader, Rajesh V Thakker, Kate E Lines","doi":"10.1530/EO-24-0055","DOIUrl":"10.1530/EO-24-0055","url":null,"abstract":"<p><p>Current models for the study of neuroendocrine tumours (NETs) are severely limited. While <i>in vitro</i> (e.g. cell lines), <i>ex vivo</i> (e.g. organoids) and <i>in vivo</i> (e.g. mice) models all exist, each has limitations. To address these limitations and collectively identify strategies to move the NET models field forward, we held an inaugural NET models meeting, hosted by our founding group: Dr Lines (Oxford), Prof. Quelle (Iowa), Dr Dayton (Barcelona), Dr Ear (Iowa), Dr Marinoni (Bern) and Dr Guenter (Alabama). This two-day meeting in Oxford (UK) was organised and supported by Bioscientifica Ltd and was solely dedicated to the discussion of NET models. The meeting was attended by ∼30 international researchers (from the UK, EU, Israel, USA and Canada). Plenary talks were given by Prof. Thakker, who summarised NET research over the past few decades, and Dr Schrader, who described the process and pitfalls of generating new cell lines. Eight researchers also presented their work on topics ranging from human cell 3D bioprinting to zebrafish models and included novel ideas and improvements on current concepts. This was followed by an interactive workshop, where discussion topics included a summary of currently available NET models, limitations of these models, barriers to developing new models, and how we can address these issues going forward. This white paper summarises the key points raised in these discussions and the future aspirations of the NET Models Consortium. The next meeting will take place in Oxford (UK) in 2025; contact contact@netcancerfoundation.com for more information.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240055"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017444","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":"Everything you ever wanted to know about cancer stem cells in neuroendocrine neoplasms but were afraid to ask.","authors":"Ignacio Ruz-Caracuel, Sergio Pedraza-Arevalo, Teresa Alonso-Gordoa, Javier Molina-Cerrillo, Julie Earl, Bruno Sainz","doi":"10.1530/EO-24-0006","DOIUrl":"10.1530/EO-24-0006","url":null,"abstract":"<p><p>While the role of cancer stem cells (CSCs) in tumorigenesis, chemoresistance, metastasis, and relapse has been extensively studied in solid tumors, such as adenocarcinomas or sarcomas, the same cannot be said for neuroendocrine neoplasms (NENs). While lagging, CSCs have been described in numerous NENs, including gastrointestinal and pancreatic NENs (PanNENs), and they have been found to play critical roles in tumor initiation, progression, and treatment resistance. However, it seems that there is still skepticism regarding the role of CSCs in NENs, even in light of studies that support the CSC model in these tumors and the therapeutic benefits of targeting them. For example, in lung neuroendocrine carcinoids, a high percentage of CSCs have been found in atypical carcinoids, suggesting the presence of CSCs in these cancers. In PanNENs, CSCs marked by aldehyde dehydrogenases or CD90 have been identified, and targeting CSCs with inhibitors of molecular pathways has shown therapeutic potential. Overall, while evidence exists for the presence of CSCs in NENs, either the CSC field has neglected NENs or the NEN field has not fully embraced the CSC model. Both might apply and/or may be a consequence of the fact that NENs are a relatively rare and heterogeneous tumor entity, with confusing histology and nomenclature to match. Regardless, this review intends to summarize our current knowledge of CSCs in NENs and highlight the importance of understanding the role of CSCs in the biology of these rare tumors, with a special focus on developing targeted therapies to improve patients' outcomes.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240006"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017442","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":"Alternative splicing generates isoform diversity in <i>MEN1</i>.","authors":"Anassuya Ramachandran, Polona Le Quesne Stabej, Veronica Boyle, Marianne S Elston, Sharon Pattison, Ben Lawrence, Cris Print","doi":"10.1530/EO-24-0014","DOIUrl":"10.1530/EO-24-0014","url":null,"abstract":"<p><p>Although the gene <i>MEN1</i> has a long-standing association with cancer, its mechanisms of action remain incompletely understood, acting both as a tumour suppressor in neuroendocrine tumours and as an oncogene in leukaemia. The best-characterised isoform of the encoded protein, MENIN, is the 610-amino acid MENIN isoform 2. We hypothesise that some of the complexity of <i>MEN1</i> biology can be attributed to a currently unappreciated contribution of different MENIN isoforms. Through <i>in silico</i> data mining, we show alternative splicing along the entire length of <i>MEN1</i>. Splice junction data suggest that the transcript encoding MENIN isoform 2 is the most abundant in all tissues examined, making a strong argument for this to be the reference transcript/protein isoform of <i>MEN1</i>. We also report novel splicing events, including a novel exon from within intron 7 that is relatively highly expressed in many tissues. These splicing events are predicted to contribute to MENIN diversity by generating isoforms with in-frame insertions, deletions or unique amino termini that, in turn, could have altered interactions with partner proteins. Finally, we have compiled 2574 unique genomic variants reported in <i>MEN1</i> within somatic and germline databases and have identified several variants that could impact individual MENIN isoforms. We have also collated studies pertinent to MENIN function in the literature and summarised the impact of <i>MEN1</i> variants on 74 biological variables. We propose a set of four <i>MEN1</i> variants, MENIN^L22R, MENIN^H139D, MENIN^A242V and MENIN^W436R, that represent a cohort with different biological properties, which should be investigated concurrently to better dissect MENIN function.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240014"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796671","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":"Predictors of hypocalcaemia and hypoparathyroidism in patients undergoing thyroidectomy for benign and malignant pathologies.","authors":"Jino Johns Lalitha, Natarajan Ramalingam, Remya Rajan, Jeyashanth Riju, Antony Abraham Paulose, Rajiv Charles Michael, Amit Jiwan Tirkey, Twisha Adhikari, Shalini Sahu, R Nagayazhini","doi":"10.1530/EO-24-0022","DOIUrl":"10.1530/EO-24-0022","url":null,"abstract":"<p><strong>Objective: </strong>To analyse the risk factors of hypoparathyroidism and hypocalcaemia after total thyroidectomy.</p><p><strong>Methods: </strong>Clinical data of patients who underwent total thyroidectomy at a tertiary care hospital in southern part of India were collected retrospectively from January 2021 to May 2023. Multivariate logistic regression was used to analyse the risk factors associated with transient hypoparathyroidism and hypocalcaemia separately.</p><p><strong>Results: </strong>A total of 300 patients who underwent total thyroidectomy were enroled. The median age of the study population was 41 years, and 70% were females. Histopathological examination showed that 80.3% had thyroid cancer. The incidence of postoperative transient hypoparathyroidism was 26.7%, while postoperative transient hypocalcaemia was 12.3%. Multivariate analysis showed that the presence of hypothyroidism before surgery (OR = 3.230, 95% CI: 1.368-7.624, <i>P</i> = 0.007), performing central compartment neck dissection (CCND) (OR = 2.196, 95% CI: 1.133-4.257, <i>P</i> = 0.02) and parathyroid gland in the surgical specimen (OR = 5.547, 95% CI: 3.065-10.036, <i>P</i> < 0.0001) were independent predictors of postoperative transient hypoparathyroidism. Female gender (OR = 2.689, 95% CI: 1.049-6.895, <i>P</i> = 0.039), presence of parathyroid in the surgical specimen (OR = 1.067, 95% CI: 0.367-8.438, <i>P</i> = 0.004) and performing CCND (OR = 2.192, 95% CI: 0.990-4.850, <i>P</i> = 0.05) were independent predictors of postoperative transient hypocalcaemia.</p><p><strong>Conclusion: </strong>Hypoparathyroidism and hypocalcaemia after thyroid surgery are common, and most of them are transient. The independent predictors of hypoparathyroidism and hypocalcaemia differ. Hypoparathyroidism appears to be a better predictor for patients who will develop postoperative hypocalcaemia.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240022"},"PeriodicalIF":0.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795873","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":"Time toxicity of lutetium 177 in gastroenteropancreatic neuroendocrine tumours.","authors":"Marcos Daniel Bortz, Andres Rodriguez, Maria Romina Luca, Federico Waisberg, Diego Enrico, Berenice Freile, Greta Catani, Federico Esteso, Martina Musumeci, Eliana Vazquez, Matías Chacón, Juan Manuel O'Connor, Silvina Racioppi","doi":"10.1530/EO-24-0028","DOIUrl":"10.1530/EO-24-0028","url":null,"abstract":"<p><strong>Objectives: </strong>We aim to investigate the time toxicity of patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate in a single institution.</p><p><strong>Design: </strong>This is a retrospective cohort study.</p><p><strong>Methods: </strong>All patients with gastroenteropancreatic neuroendocrine tumours treated with Lutetium-177 Dotatate at the Alexander Fleming Institute were included. Our primary endpoint was to evaluate time toxicity, which accounted for every day that the patient had contact with any department of any healthcare institution.</p><p><strong>Results: </strong>Our cohort included 21 patients with metastatic disease, female sex 86%, and a median age of 55 (IQR 44-63). The primary tumour site was the small intestine in 47.6% of the cases. The median number of previous systemic treatments for advanced disease was two (IQR 2-3). The overall response rate was 19%, and 66.6% had clinical benefit. The median calculated 'time toxicity' was 11 days (IQR 8-18), representing 5.7% of the total treatment duration. The main contributors to time toxicity included infusion days, blood draws, radiological scans, and hospitalisations (median of 4 days for each).</p><p><strong>Conclusion: </strong>Lutetium-177 Dotatate treatment for gastroenteropancreatic neuroendocrine tumours was associated with low time toxicity, excellent tolerability, a good response and prolonged PFS, of which the median was not reached in the short follow-up we present. Newer treatments with different mechanisms of action provide longer survival and widen the landscape of choices. Understanding new clinical endpoints is important for the transition into a more modern clinical practice, strengthening personalised and patient-oriented strategies.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240028"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796263","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":"Multifaceted modeling of small intestinal neuroendocrine tumors.","authors":"Stephen Gabriel Andrews, Steven D Forsythe, James P Madigan, Samira Mercedes Sadowski","doi":"10.1530/EO-24-0038","DOIUrl":"10.1530/EO-24-0038","url":null,"abstract":"<p><p>Small intestinal neuroendocrine tumors, siNETs, are a group of rare cancers that arise from neuroendocrine cells in the lining of the jejunum and ileum, which are either classified as tumors, siNETs, or small intestinal neuroendocrine carcinomas, siNECs. Current treatment strategies for low-grade tumors include surgical resection, peptide radionucleotide receptor therapy, and somatostatin analogues, while high-grade and recurrent tumors may receive cytotoxic chemotherapy. These limited treatment options are linked to the lack of representative models that can both reflect the biology of the tumor and are amenable to mid-to-high throughput experimentation. Cell line generation is challenging considering the indolent nature of primary lesions, although some attempts have been successful using a variety of methods and include the primary P-STS line and those derived from metastatic lesions, including GOT1, CNDT2.5, and HC45. Patient-derived modeling, including organoids and xenografting, have allowed for multicellular and 3D representations of the original tumor. These specific models allow for multicellular populations derived from the tumor, providing better tumor representation for use in drug screening and <i>in vitro</i> assays. Currently, there are limited, although increasing, published models of siNETs implanted as xenografts in mice and zebrafish. As these cellular and animal models provide insights into siNET biology, theragnostic modeling has provided key information on the clinical progression and treatment of this disease. Significant strides toward more representative models have been made throughout the last decade. In this review, details of these attempts as well as future directions and strategies for more robust models will be addressed.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240038"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795683","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":"Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.","authors":"Emma Boehm, Terry Hung, Tim Akhurst, Ramin Alipour, Cherie Chiang, Rodney J Hicks, Michael S Hofman, Aravind S Ravi Kumar, Nirupa Sachithanandan, Javad Saghebi, Michael Michael, Grace Kong","doi":"10.1530/EO-24-0013","DOIUrl":"10.1530/EO-24-0013","url":null,"abstract":"<p><strong>Background: </strong>Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes. Peptide receptor radionuclide therapy (PRRT) is a rational option for hormone and disease control in ECS caused by NEN with high somatostatin receptor (SSTR) expression.</p><p><strong>Aim: </strong>To describe the characteristics and outcomes of patients with ECS treated with PRRT.</p><p><strong>Methods: </strong>Single-centre, retrospective analysis of imaging, biochemistry and outcomes of seven consecutive patients with ECS caused by metastatic GEPNEN treated with PRRT from 2006 to 2023.</p><p><strong>Results: </strong>Patients were aged 17-75 (female <i>n</i> = 6). The primary site was the pancreas (5/7) and rectum (2/7). Six patients were on medical therapy for ECS at baseline (one had a previous BA). A median of 34.4 GBq of [¹⁷⁷Lu]Lu-DOTA-octreotate was given. [⁹⁰Y]Y-DOTA-octreotate (one patient) and [¹¹¹In]In-octreotide (one patient) were also used. Five patients had radiosensitising chemotherapy. Five patients had a flare of ECS within 1 week of PRRT cycle 1 (PRRT-C1). Following PRRT-C1, 5/7 patients had complete biochemical resolution of ECS at 1.5-6 months (four ongoing; one recurred after 12 months and had elective BA at 18 months). Best metabolic response on [¹⁸F]F-FDG PET/CT: Four patients had a complete metabolic response (CMR), and one had a partial metabolic response. PFS was 3-208 months. Two patients progressed at the first follow-up. The longest ECS remission and CMR continues at >17 years.</p><p><strong>Conclusion: </strong>PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240013"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795692","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":"Less frequent radiological exams to avoid futile response assessments from 177-LuDOTATE therapy for patients with advanced neuroendocrine tumors.","authors":"Carolina C Marques, Angelo B Brito, Eduardo N Lima, Mauro D Donadio, Rachel P Riechelmann","doi":"10.1530/EO-24-0021","DOIUrl":"10.1530/EO-24-0021","url":null,"abstract":"<p><strong>Background: </strong>177-LuDOTATE is an effective but expensive treatment for neuroendocrine tumors (NETs). Reducing treatment-related costs, such as the number of images, could improve access to 177-LuDOTATE. We evaluated early radiological tumor progression and prognostic factors in patients with NETs treated with 177-LuDOTATE.</p><p><strong>Methods: </strong>We retrospectively included all patients with NETs who received at least one cycle of 177-LuDOTATE. The primary endpoint was the rate of early radiological progression between cycles 2 and 3 (in 10-16 weeks). Secondary endpoints were progression-free survival (PFS) and overall survival (OS) according to prognostic factors (tumor grade, primary site, functioning syndrome, 177-LuDOTATE treatment line) in Cox proportional hazards models.</p><p><strong>Results: </strong>The median number of 177-LuDOTATE cycles was 3 (range 1-6) among 59 patients included. Ten (17%) patients had early progression. Among 14 patients who received ≤2 cycles of 177-LuDOTATE, ten (72%) stopped treatment due to disease progression, with five patients having a G2 (ki67: 5-25%) and 4, a G3 (ki67: 25-90%) NET. In the Cox multivariable analysis, higher grade (G2 or G3 vs G1) were significantly associated with inferior PFS and OS. The median PFS of G1, G2 and G3 NET patients were: 34.1, 11.7 and 6.1 months (<i>P</i> = 0.015), respectively.</p><p><strong>Conclusions: </strong>It is feasible to perform imaging tests after 177-LuDOTATE completion for patients with indolent NETs with the intent to avoid futile assessments. For patients with more aggressive diseases, such as G3 NETs and G2 tumors with high tumor burden, we advise to perform more frequent images during 177-LuDOTATE therapy.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240021"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634022","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":"Hereditary and clinical insights into paraganglioma and pheochromocytoma.","authors":"Caitlin B Mauer Hall, Elise M Watson, Tanushree Prasad, Chandler L Myers, Jacqueline A Mersch","doi":"10.1530/EO-24-0029","DOIUrl":"10.1530/EO-24-0029","url":null,"abstract":"<p><strong>Background: </strong>Approximately 30-40% of paragangliomas (PGLs) and pheochromocytomas (PCCs) harbor an underlying hereditary cause. Early identification of at-risk individuals is imperative given the early onset, aggressiveness of tumors, and other tumor/cancer risks associated with hereditary PGLs/PCCs. This study analyzes the clinical presentations and genetic histories of patients with PGL/PCC and/or hereditary risk to contribute to the expanding knowledge in this rare population.</p><p><strong>Methods: </strong>A retrospective chart review identified two cohorts of patients seen in cancer genetics clinics at an academic medical center and a safety-net hospital between August 2016 and December 2022. Cohort 1 consisted of patients with likely pathogenic variants (LPVs)/pathogenic variants (PVs) in hereditary PGL/PCC predisposition genes. Cohort 2 consisted of patients with a personal history of a PGL/PCC. Demographics, personal/family history, and genetic testing outcomes were analyzed.</p><p><strong>Results: </strong>A total of 560 patients met the study criteria (Cohort 1, <i>n</i> = 364; Cohort 2, <i>n</i> = 269). In Cohort 1, 77 (21.1%) patients had an incidental LPV/PV in a PGL/PCC gene. Nearly half (<i>n</i> = 36, 46.8%) were in <i>SDHx</i> genes, with a majority in <i>SDHA</i> (<i>n</i> = 21). In Cohort 2, 86 patients tested positive for 87 LPV/PV in a hereditary cancer predisposition gene. The <i>SDHx</i> genes were most likely to have an LPV/PV identified (<i>SDHB n</i> = 24, <i>SDHD n</i> = 23).</p><p><strong>Conclusions: </strong>Multigene panels identify patients at risk for hereditary PGL/PCC, many of whom are incidentally found. While <i>SDHA</i> LPV/PVs were the most frequent incidental finding, they were less common in patients with PGL/PCC, indicating the need for longitudinal studies to better understand the prevalence and penetrance of these tumors.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240029"},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633926","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":"Pituitary gigantism due to a novel <i>AIP</i> germline splice-site variant.","authors":"Elisa Lamback, Renan Lyra Miranda, Leila Chimelli, Felipe Andreiuolo, Leandro Kasuki, Luiz Eduardo Wildemberg, Mônica R Gadelha","doi":"10.1530/EO-24-0003","DOIUrl":"10.1530/EO-24-0003","url":null,"abstract":"<p><p>Pituitary gigantism is a rare pediatric disorder caused by excess growth hormone (GH) secretion. In almost 50% of cases, a genetic cause can be identified, with pathogenic variants in the aryl hydrocarbon receptor-interacting protein (<i>AIP</i>) gene being the most common. We present a case of an 11-year-old boy who exhibited progressive vision loss, associated with accelerated linear growth, and weight gain. On physical examination, he had enlarged hands, right eye amaurosis, and was already above his target height. Increased GH and IGF-I concentrations confirmed the diagnosis of pituitary gigantism. Magnetic resonance imaging showed a giant sellar lesion with supra- and para-sellar extensions. He underwent two surgeries which did not achieve a cure or visual improvement. Histopathological analysis revealed a sparsely granulated tumor, negative for somatostatin receptor type 2 (SST2) and an immunoreactivity score of 6 for somatostatin receptor type 5 (SST5). Our published artificial intelligence prediction model predicted an 83% chance of not responding to first-generation somatostatin receptor ligands. Pasireotide was therefore prescribed, and afterward cabergoline was added on. IGF-I concentrations decreased but did not normalize. We discovered a novel germline single nucleotide variant in the splicing donor region of intron 2 of the <i>AIP</i> gene (NM_003977.4:c.279+1 G>A), classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines.</p>","PeriodicalId":72907,"journal":{"name":"Endocrine oncology (Bristol, England)","volume":"4 1","pages":"e240003"},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402211","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}