{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:21:23Z","timestamp":1760059283806,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are an extremely rare malignant form of these tumors, carrying a significantly worse prognosis. Case Presentation: A 49-year-old woman, a patient in the University Hospital in Wroclaw in the Department of Endocrinology, Diabetes and Isotope Therapy, first presented with abdominal pain in 2009, when ultrasound and further examination led to the diagnosis of a tumor in the pancreas (a solid pseudopapillary tumor of the pancreas\u2014meta NET G2), and the patient underwent distal pancreatectomy with splenectomy. For ten years, she was under observation, and her symptoms, such as abdominal pain, nausea, weight loss, and general weakness, reappeared in 2019. Then, magnetic resonance imaging (MRI) showed a lesion in the liver, and further histopathology revealed neuroendocrine tumor (NET) metastasis to the liver. In 2022, the patient presented with loss of consciousness and convulsion, loss of weight, and hypoglycemia after meals. In April 2022, the daily glycemic profile was recorded and a 72 h fasting test was performed; however, their results excluded insulinoma. Positron emission tomography\u2013computed tomography (PET-CT) with 18F-fluorodeoxyglucose (18F-FDG) and PET with gallium-68-DOTA-(Tyr3)-octreotate (68Ga-DOTA-TATE) showed a metastatic proliferative process in the liver. Persistent hypoglycemia led to another hospitalization in May 2022, and repeated tests allowed for the diagnosis of insulinoma. Treatment with somatostatin analogs and diazoxide was started. A CT scan in November 2022 and a PET scan in January 2023 showed new metastases to the liver, bones, and cervical lymph nodes, and it was decided to intensify the treatment. In May 2023, the patient was qualified for Lutathera treatment for insulinoma at the University Clinical Hospital in Pozna\u0144. In June 2023, another disturbing symptom was reported by the patient, a painful lump in the breast. During diagnostics, metastases with high proliferation markers were found in both breasts. Two months later, in August 2023, the patient received another dose of Lutathera. In October 2023, significant progression of liver lesions, metastases to bones of the spine, ribs, and pelvis, and periaortic and pelvic lymphadenopathy were found as well as elevated values of neuron-specific enolase and calcitonin. The patient was also referred to the Palliative Medicine Home Hospice. In consultation with the Lower Silesian Cancer Center, the decision was made to forgo further treatment with PRRT and initiate systemic chemotherapy. Despite the chosen treatment, the patient died on 27\/DEC\/2023. Conclusions: This case report can serve clinicians, as it presents a case of an extremely rare and insidious tumor, metastatic insulinoma.<\/jats:p>","DOI":"10.3390\/jcm14124028","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T11:08:31Z","timestamp":1749208111000},"page":"4028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["History of an Insidious Case of Metastatic Insulinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5026-0344","authenticated-orcid":false,"given":"Katarzyna","family":"Antosz-Popio\u0142ek","sequence":"first","affiliation":[{"name":"Student Scientific Group of Endocrinology, Wroclaw Medical University, Wybrze\u017ce Pasteura 4, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9185-038X","authenticated-orcid":false,"given":"Joanna","family":"Koga-Batko","sequence":"additional","affiliation":[{"name":"Student Scientific Group of Endocrinology, Wroclaw Medical University, Wybrze\u017ce Pasteura 4, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Suchecki","sequence":"additional","affiliation":[{"name":"Student Scientific Group of Endocrinology, Wroclaw Medical University, Wybrze\u017ce Pasteura 4, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3456-2891","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Stopa","sequence":"additional","affiliation":[{"name":"Student Scientific Group of Endocrinology, Wroclaw Medical University, Wybrze\u017ce Pasteura 4, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Zawadzka","sequence":"additional","affiliation":[{"name":"Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrze\u017ce Pasteura 4, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0141ukasz","family":"Hajac","sequence":"additional","affiliation":[{"name":"Neuroendocrine Cancer Unit, Lower Silesian Oncology, Pulmonology and Hematology Center, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2360-6596","authenticated-orcid":false,"given":"Marek","family":"Bolanowski","sequence":"additional","affiliation":[{"name":"Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrze\u017ce Pasteura 4, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Jawiarczyk-Przyby\u0142owska","sequence":"additional","affiliation":[{"name":"Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrze\u017ce Pasteura 4, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13318","DOI":"10.1111\/jne.13318","article-title":"European Neuroendocrine Tumor Society 2023 Guidance Paper for Functioning Pancreatic Neuroendocrine Tumour Syndromes","volume":"35","author":"Hofland","year":"2023","journal-title":"J. Neuroendocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1007\/s00268-020-05445-x","article-title":"Malignant Insulinoma: A Rare Form of Neuroendocrine Tumor","volume":"44","author":"Sada","year":"2020","journal-title":"World J. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s40618-019-01091-w","article-title":"The Functioning Side of the Pancreas: A Review on Insulinomas","volume":"43","author":"Maggio","year":"2020","journal-title":"J. Endocrinol. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1159\/000080735","article-title":"Insulinoma","volume":"80","year":"2004","journal-title":"Neuroendocrinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2217\/fon.09.165","article-title":"Insulinoma: Pathophysiology, Localization and Management","volume":"6","author":"Shin","year":"2010","journal-title":"Future Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1097\/MPA.0000000000000110","article-title":"A Systematic Review of Localization, Surgical Treatment Options, and Outcome of Insulinoma","volume":"43","author":"Mehrabi","year":"2014","journal-title":"Pancreas"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.soc.2015.12.003","article-title":"Clinical Presentation and Diagnosis of Pancreatic Neuroendocrine Tumors","volume":"25","author":"Anderson","year":"2016","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3748\/wjg.v19.i6.829","article-title":"Diagnosis and Management of Insulinoma","volume":"19","author":"Okabayashi","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1007\/s11605-016-3118-y","article-title":"Giant Malignant Insulinoma","volume":"20","year":"2016","journal-title":"J. Gastrointest. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"124078","DOI":"10.1155\/2011\/124078","article-title":"Metastatic Insulinoma in a Patient with Type 2 Diabetes Mellitus: Case Report and Review of the Literature","volume":"2011","author":"Abbasakoor","year":"2011","journal-title":"Int. J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.suc.2009.06.009","article-title":"Insulinoma","volume":"89","author":"Mathur","year":"2009","journal-title":"Surg. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/cncr.21179","article-title":"Malignant Insulinoma: Spectrum of Unusual Clinical Features","volume":"104","author":"Hirshberg","year":"2005","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.amjsurg.2020.08.003","article-title":"Comparison of Benign and Malignant Insulinoma","volume":"221","author":"Sada","year":"2021","journal-title":"Am. J. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1365-2265.2011.04145.x","article-title":"New Therapeutic Options for Metastatic Malignant Insulinomas","volume":"75","author":"Kwekkeboom","year":"2011","journal-title":"Clin. Endocrinol."},{"key":"ref_15","first-page":"1302","article-title":"Insulinomas: From Diagnosis to Treatment. A Review of the Literature","volume":"25","author":"Moris","year":"2020","journal-title":"JBUON"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/cen.13528","article-title":"Multidisciplinary Management of Refractory Insulinomas","volume":"88","author":"Brown","year":"2018","journal-title":"Clin. Endocrinol."},{"key":"ref_17","first-page":"129","article-title":"Solid Pseudopapillary Tumor of the Pancreas","volume":"41","author":"Gursan","year":"2009","journal-title":"Eurasian J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s13244-011-0102-7","article-title":"Part 1: CT Characterisation of Pancreatic Neoplasms: A Pictorial Essay","volume":"2","author":"Galvin","year":"2011","journal-title":"Insights Imaging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0025-6196(12)62083-7","article-title":"Functioning Insulinoma\u2014Incidence, Recurrence, and Long-Term Survival of Patients: A 60-Year Study","volume":"66","author":"Service","year":"1991","journal-title":"Mayo Clin. Proc."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, J., Jiang, R., Hong, X., Wu, H., Han, X., and Wu, W. (2023). Metastatic Insulinoma: Exploration from Clinicopathological Signatures and Genetic Characteristics. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1109330"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yu, J., Ping, F., Zhang, H., Li, W., Yuan, T., Fu, Y., Feng, K., Xia, W., Xu, L., and Li, Y. (2018). Clinical Management of Malignant Insulinoma: A Single Institution\u2019s Experience over Three Decades. BMC Endocr. Disord., 18.","DOI":"10.1186\/s12902-018-0321-8"},{"key":"ref_22","first-page":"65","article-title":"Insulinoma-Related Endogenous Hypoglycaemia with a Negative Fasting Test: A Case Report and Literature Review","volume":"9","year":"2022","journal-title":"Eur. J. Case Rep. Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1159\/000217786","article-title":"Serum Neuron-Specific Enolase in Diagnosis and Follow-Up of Gastrointestinal Neuroendocrine Tumors","volume":"13","author":"Mariani","year":"1992","journal-title":"Tumor Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/0016-5085(86)90625-6","article-title":"Immunohistochemical Study of Neuron-Specific Enolase and CA 19-9 in Pancreatic Disorders. The Value of Neuron-Specific Enolase as a Marker for Islet Cell and Nerve Tissue","volume":"91","author":"Iwase","year":"1986","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s11864-023-01085-0","article-title":"Management of Functional Pancreatic Neuroendocrine Neoplasms","volume":"24","author":"Magi","year":"2023","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.5604\/01.3001.0014.3056","article-title":"Somatostatin Analogues in the Therapy of Neuroendocrine Tumors: Indications, Contraindications, Side-Effects","volume":"74","author":"Polowczyk","year":"2020","journal-title":"Postep. Hig. Med. Dosw."},{"key":"ref_27","first-page":"73","article-title":"Polish Recommendation for Diagnosis and Treatment of Gastroenteropancreatic Tumors (GEP NET)","volume":"2","author":"Jeziorski","year":"2006","journal-title":"Oncol. Clin. Pract."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa1607427","article-title":"Phase 3 Trial of 177 Lu-Dotatate for Midgut Neuroendocrine Tumors","volume":"376","author":"Strosberg","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e330","DOI":"10.4158\/ACCR-2019-0086","article-title":"Long-Term Effect of 177Lu-Dotatate on Severe and Refractory Hypoglycemia Associated with Malignant Insulinoma","volume":"5","author":"Iglesias","year":"2019","journal-title":"AACE Clin. Case Rep."},{"key":"ref_30","first-page":"252159","article-title":"Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog","volume":"2013","author":"Costa","year":"2013","journal-title":"Case Rep. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/RLU.0000000000001023","article-title":"Metastatic Insulinoma Pancreatic Neuroendocrine Tumor Treated with 177Lu-DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy: A Suggested Protocol","volume":"41","author":"Makis","year":"2016","journal-title":"Clin. Nucl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E415","DOI":"10.1097\/RLU.0000000000002500","article-title":"Metastatic Insulinoma Controlled by Targeted Radionuclide Therapy with 177Lu-DOTATATE in a Patient with Solitary Kidney and MEN-1 Syndrome","volume":"44","author":"Novruzov","year":"2019","journal-title":"Clin. Nucl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13474","DOI":"10.1111\/jne.13474","article-title":"The Role of Combined FDG and SST PET\/CT in Neuroendocrine Tumors","volume":"37","author":"Fortunati","year":"2025","journal-title":"J. Neuroendocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41416-022-02061-5","article-title":"Dual [68Ga]DOTATATE and [18F]FDG PET\/CT in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicentre Validation of the NETPET Score","volume":"128","author":"Chan","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"585","DOI":"10.5603\/EP.a2020.0070","article-title":"Endoscopic Ultrasound-Guided Ethanol Ablation of Insulinoma","volume":"71","author":"Zalewska","year":"2020","journal-title":"Endokrynol. Pol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/cncy.22242","article-title":"Insulinoma-Associated Protein 1 (INSM1) Is a Robust Marker for Identifying and Grading Pancreatic Neuroendocrine Tumors","volume":"128","author":"Kim","year":"2020","journal-title":"Cancer Cytopathol."},{"key":"ref_37","first-page":"3500","article-title":"INSM1 Promotes Breast Carcinogenesis by Regulating C-MYC","volume":"13","author":"Guan","year":"2023","journal-title":"Am. J. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.pathol.2020.07.004","article-title":"INSM1 Is a Novel Prognostic Neuroendocrine Marker for Luminal B Breast Cancer","volume":"53","author":"Razvi","year":"2021","journal-title":"Pathology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/00000421-198912000-00008","article-title":"Aggressive Insulinoma with Bone Metastases","volume":"12","author":"Hesdorffer","year":"1989","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_40","first-page":"125","article-title":"Diagnosis and Management of Insulinoma: Current Best Practice and Ongoing Developments","volume":"5","author":"Libutti","year":"2015","journal-title":"Res. Rep. Endocr. Disord."},{"key":"ref_41","first-page":"EP144","article-title":"Insulinoma- from Diagnosis to Full Recovery. Case Study","volume":"49","author":"Lewicki","year":"2017","journal-title":"Endocr. Abstr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yu, Z., Wang, Y., Sun, Y., Wang, Y., Tian, Y., Ma, Q., and Fu, Y. (2021). Case Report: Insulinoma Presenting as Excessive Daytime Somnolence. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.712392"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Oziel-Taieb, S., Maniry-Quellier, J., Chanez, B., Poizat, F., Ewald, J., and Niccoli, P. (2022). Pasireotide for Refractory Hypoglycemia in Malignant Insulinoma- Case Report and Review of the Literature. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.860614"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1136\/bcr-2020-238238","article-title":"Case Report of a Pancreatic Insulinoma Misdiagnosed as Epilepsy","volume":"14","author":"Williams","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s13256-023-03963-5","article-title":"Insulinoma with Peripheral Neuropathy: A Case Report","volume":"17","author":"Reverdito","year":"2023","journal-title":"J. Med. Case Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108397","DOI":"10.1016\/j.ijscr.2023.108397","article-title":"A Rare Case of Insulinoma Presented with Neurological Manifestations: A Case Report","volume":"108","author":"AlKhamisy","year":"2023","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_47","first-page":"EP9","article-title":"Case Report: Management of a Patient with Malignant Insulinoma","volume":"56","author":"Topaloglu","year":"2018","journal-title":"Endocr. Abstr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"69","DOI":"10.11604\/pamj.2022.42.69.34839","article-title":"Varied Presentations of Pancreatic Insulinoma: A Case Report","volume":"42","author":"Nashidengo","year":"2022","journal-title":"Pan Afr. Med. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"377","DOI":"10.15761\/CCRR.1000412","article-title":"Pancreatic Insulinoma: Case Report and Review of the Literature","volume":"4","author":"Amiri","year":"2018","journal-title":"Clin. Case Rep. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tarris, G., Rouland, A., Guillen, K., Loffroy, R., Lariotte, A.C., Rat, P., Bouillet, B., Andrianiaina, H., Petit, J.M., and Martin, L. (2023). Case Report: Giant Insulinoma, a Very Rare Tumor Causing Hypoglycemia. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1125772"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4028\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:47:51Z","timestamp":1760032071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/12\/4028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14124028"],"URL":"https:\/\/doi.org\/10.3390\/jcm14124028","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,6,6]]}}}