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Bondarenko D, Thelmo FL, Shirodkar MK. Metastatic Insulinoma Managed With Continuous Glucose Monitoring in a Young Female Patient. JCEM CASE REPORTS 2025; 3:luaf005. [PMID: 39866917 PMCID: PMC11758144 DOI: 10.1210/jcemcr/luaf005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Indexed: 01/28/2025]
Abstract
Insulinomas are rare neuroendocrine neoplasms and causes of hypoglycemia. They present with neuroglycopenic symptoms, including confusion and seizures. Suspected diagnosis must be confirmed through bloodwork and imaging. The majority of insulinomas are benign and cured surgically; less than 10% of insulinomas are malignant. Malignant insulinomas present a unique and rare challenge in managing persistent hypoglycemia and tumor burden. We present a case of a young woman who presented with Whipple triad and high-grade masses in her pancreas, liver, and distant lymph node metastases on imaging. Insulinoma was diagnosed. Hypoglycemia was managed with continuous dextrose infusion, diazoxide, and lanreotide. She was discharged on medical management and a continuous glucose monitor. Her metastatic disease is being treated with a capecitabine and temozolomide (CAPTEM) regimen showing 30% reduction in tumor burden. In conjunction with the National Institutes of Health, she is undergoing evaluation with numerous neuroendocrine tumor surgeons for cytoreductive surgery.
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Affiliation(s)
- Darya Bondarenko
- Department of Medicine, Jefferson Abington Hospital, Abington, PA 19001, USA
| | - Franklin L Thelmo
- ChristianaCare Endocrinology Specialists, ChristianaCare Health System, Newark, DE 19713, USA
| | - Monika K Shirodkar
- Division of Endocrinology, Diabetes & Metabolic Diseases, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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Popa SG, Golli AL, Matei CF, Sonei AN, Vere C, Cimpeanu R, Munteanu M, Munteanu A. Pancreatic Neuroendocrine Tumors-Diagnostic Pitfalls of Non-Diabetic Severe Hypoglycemia: Literature Review and Case Report. Diagnostics (Basel) 2025; 15:337. [PMID: 39941267 PMCID: PMC11816404 DOI: 10.3390/diagnostics15030337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/23/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Hypoglycemia in the case of persons without diabetes is a rare event, being usually, initially misinterpreted based on the symptoms that can mimic various diseases, especially of a neuro-psychiatric nature. In the case of the identification of insulin-mediated hypoglycemia, the evaluation of pancreatic neuroendocrine tumors, which represent the most common and worrisome causes of non-diabetic insulin-mediated hypoglycemia, must be considered. Case Report: We present the case of a 57-year-old patient, hospitalized for a history of approximately one month of recurrent episodes of symptoms suggestive for severe hypoglycemia. The biological evaluation performed during an episode of hypoglycemia showed a plasma glucose value of 44 mg/dL, insulinemia 16.3 µU/mL, C peptide 3.72 ng/mL, HbA1c 4.99%, absence of urinary ketone bodies and anti-insulin antibodies <0.03 U/mL. The CT and MRI examination showed a 15.3/15 mm rounded tumor in the pancreatic corporeo-caudal region. The pancreatic tumor formation was enucleated and the histopathological and immunohistochemical analysis confirmed the diagnosis of the pancreatic neuroendocrine tumor with a positive reaction for chromogranin A, synaptophysin and insulin, without malignancy features (Ki 67 positive in 1% of the tumor cells). The postoperative evolution was favorable, without episodes of hypoglycemia, the fasting insulinemia one day after surgery being 4.1 µU/mL and HbA1c at three weeks postoperatively being 5.51%. Conclusions: The management of patients with hyperinsulinemic hypoglycemia secondary to insulinoma involves multidisciplinary collaboration with an important role in recognizing symptoms suggestive of hypoglycemia in a person without diabetes, initiating biological and imaging evaluation, establishing the optimal therapeutic option and histopathological confirmation.
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Affiliation(s)
- Simona Georgiana Popa
- Department of Diabetes, Nutrition and Metabolic Diseases, University of Medicine and Pharmacy, 200349 Craiova, Romania;
| | - Andreea Loredana Golli
- Department of Public Health and Healthcare Management, University of Medicine and Pharmacy, 200349 Craiova, Romania
| | - Cristina Florentina Matei
- Department of Diabetes, Nutrition and Metabolic Diseases, Emergency County Hospital, 200642 Craiova, Romania; (C.F.M.); (A.N.S.)
| | - Alexandra Nicoleta Sonei
- Department of Diabetes, Nutrition and Metabolic Diseases, Emergency County Hospital, 200642 Craiova, Romania; (C.F.M.); (A.N.S.)
| | - Cristin Vere
- Department of Gastroenterology, University of Medicine and Pharmacy, 200349 Craiova, Romania; (C.V.); (R.C.)
| | - Radu Cimpeanu
- Department of Gastroenterology, University of Medicine and Pharmacy, 200349 Craiova, Romania; (C.V.); (R.C.)
| | - Marian Munteanu
- Department of Surgery, University of Medicine and Pharmacy, 200349 Craiova, Romania; (M.M.); (A.M.)
| | - Alexandru Munteanu
- Department of Surgery, University of Medicine and Pharmacy, 200349 Craiova, Romania; (M.M.); (A.M.)
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Cidade-Rodrigues C, Santos AP, Calheiros R, Santos S, Matos C, Moreira AP, Inácio I, Souteiro P, Oliveira J, Jácome M, Pereira SS, Henrique R, Torres I, Monteiro MP. Non-functional alpha-cell hyperplasia with glucagon-producing NET: a case report. Front Endocrinol (Lausanne) 2024; 15:1405835. [PMID: 39309109 PMCID: PMC11412808 DOI: 10.3389/fendo.2024.1405835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 08/08/2024] [Indexed: 09/25/2024] Open
Abstract
Introduction Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented. Case report A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient's past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (<209), and 68Ga-SSTR PET/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative 68Ga-SSTR PET/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis. Discussion and conclusion This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome.
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Affiliation(s)
| | - Ana Paula Santos
- Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
- Research Center of IPO Porto (CI-IPOP), RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), Porto, Portugal
| | - Raquel Calheiros
- Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Sara Santos
- Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Catarina Matos
- Hospital de Braga, Unidade Local de Saúde de Braga, Braga, Portugal
| | - Ana Paula Moreira
- Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal
| | - Isabel Inácio
- Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Pedro Souteiro
- Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Joana Oliveira
- Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Manuel Jácome
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Sofia S. Pereira
- Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
- Laboratory of Integrative and Translocation Research in Population Health (ITR), Porto, Portugal
| | - Rui Henrique
- Research Center of IPO Porto (CI-IPOP), RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), Porto, Portugal
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
- Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
| | - Isabel Torres
- Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Mariana P. Monteiro
- Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
- Laboratory of Integrative and Translocation Research in Population Health (ITR), Porto, Portugal
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Giri S, Sahoo J. Advancements in medical treatment for pancreatic neuroendocrine tumors: A beacon of hope. World J Gastroenterol 2024; 30:1670-1675. [PMID: 38617746 PMCID: PMC11008371 DOI: 10.3748/wjg.v30.i12.1670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/29/2024] [Accepted: 03/07/2024] [Indexed: 03/28/2024] Open
Abstract
This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors (pan-NETs), emphasizing tailored approaches for specific subtypes. Cytoreductive surgery and somatostatin analogs (SSAs) play pivotal roles in managing tumors, while palliative options such as molecular targeted therapy, peptide receptor radionuclide therapy, and chemotherapy are reserved for SSA-refractory patients. Gastrinomas, insulinomas, glucagonomas, carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies. Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research. This review underscores the evolving landscape of pan-NET treatment, offering renewed hope and improved outcomes for patients facing this complex disease.
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Affiliation(s)
- Somdatta Giri
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006, India
| | - Jayaprakash Sahoo
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006, India
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Melhorn P, Mazal P, Wolff L, Kretschmer-Chott E, Raderer M, Kiesewetter B. From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms. Ther Adv Med Oncol 2024; 16:17588359241240316. [PMID: 38529270 PMCID: PMC10962050 DOI: 10.1177/17588359241240316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 02/27/2024] [Indexed: 03/27/2024] Open
Abstract
Somatostatin analogs (SSA), specifically octreotide and lanreotide, have demonstrated antiproliferative effects in patients with neuroendocrine tumors (NET), a group of rare malignancies of diverse origin and presentation. A prominent feature of NET cells is the expression of G protein-coupled receptors called somatostatin receptors (SSTR). Although these SSTR are not uniformly present in NET, they can be instrumental in the diagnosis and treatment of NET. Apart from their application in nuclear imaging and radionuclide therapy, SSA have proven invaluable in the treatment of hormonal syndromes associated with certain NET (antisecretory effects of SSA), but it took more than two decades to convincingly demonstrate the antiproliferative effects of SSA in metastatic NET with the two pivotal studies PROMID and CLARINET. The current review summarizes three decades of SSA treatment and provides an overview of the clinical trial landscape for SSA monotherapy and combination therapy, including clinical implications and quality of life aspects, as well as ongoing fields of research.
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Affiliation(s)
- Philipp Melhorn
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Peter Mazal
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Ladislaia Wolff
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Elisabeth Kretschmer-Chott
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Markus Raderer
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria
| | - Barbara Kiesewetter
- Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
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Hofland J, Refardt JC, Feelders RA, Christ E, de Herder WW. Approach to the Patient: Insulinoma. J Clin Endocrinol Metab 2024; 109:1109-1118. [PMID: 37925662 PMCID: PMC10940262 DOI: 10.1210/clinem/dgad641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/02/2023] [Accepted: 10/27/2023] [Indexed: 11/07/2023]
Abstract
Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with the Whipple triad: (1) symptoms, signs, or both consistent with hypoglycemia; (2) a low plasma glucose measured at the time of the symptoms and signs; and (3) relief of symptoms and signs when the glucose is raised to normal. Nonmetastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive." The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options.
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Affiliation(s)
- Johannes Hofland
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
| | - Julie C Refardt
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
- ENETS Center of Excellence, Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland
| | - Richard A Feelders
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
| | - Emanuel Christ
- ENETS Center of Excellence, Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland
| | - Wouter W de Herder
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
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