CASE REPORT article
Front. Endocrinol.
Sec. Neuroendocrine Science
Shift in Secretory Profile of a pNET: From Indolent Glucagonoma to Aggressive Insulinoma – A Case Report
Provisionally accepted
- Portuguese Oncology Institute, Porto, Portugal
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Pancreatic neuroendocrine tumors (pNETs) can change their hormonal profile over time, leading to new clinical syndromes that significantly impact prognosis and management. We report the case of a patient with a metastatic glucagon-secreting pNET who, after 14 years of disease and multiple treatment lines, developed insulin hypersecretion and severe, treatment-refractory hypoglycemia. Despite several strategies, including diazoxide, somatostatin analogues, glucocorticoids, everolimus, peptide receptor radionuclide therapy, and continuous glucose and glucagon infusions, glycemic control was not achieved, and the patient ultimately died from treatment complications. This case highlights the clinical challenges of managing metachronous hormonal syndromes and the importance of long-term endocrine follow-up in pNET patients. It also emphasizes the limitations of current therapeutic strategies and the urgent need for new treatment options, including alpha-emitting radiopharmaceuticals, which may offer improved disease and symptom control in advanced, insulin-secreting pNETs.
Keywords: case report, Pancreatic neuroendocrine tumor, Insulinoma, Glucagonoma, Hypoglycemia
Received: 21 Oct 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Gil dos Santos, Calheiros, Oliveira, Santos and Souteiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sara Gil dos Santos
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