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Peer-reviewedCC BY-NC-NDESMO gastrointestinal oncology

Prevention and management of hormonal crisis in neuroendocrine tumors undergoing PRRT (peptide receptor radionuclide therapy): a systematic review.

  • G Arrivi1
  • M Pagnanelli2,3
  • G Puliani4
  • A Zerbi2,3
  • S Partelli5
  • F Panzuto6,7
7 affiliations
  1. 1Oncology Unit, Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, ENETS Center of Excellence, Rome, Italy.
  2. 2Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  3. 3Pancreatic Surgery Unit, Department of Biomedical Sciences, IRCCS Humanitas Research Hospital, Milan, Italy.
  4. 4Oncological Endocrinology Unit, Department of Clinical and Oncological Research, Regina Elena National Cancer Institute IRCCS, Rome, Italy.
  5. 5Pancreatic and Transplant Surgery Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  6. 6Digestive Disease Unit, Department of Medical and Surgical Sciences and Translational Medicine, Sant' Andrea University Hospital, ENETS Center of Excellence, Rome, Italy.
  7. 7Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy.
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Abstract

Peptide receptor radionuclide therapy (PRRT) is an established treatment of advanced well-differentiated neuroendocrine tumors (NETs) expressing somatostatin receptors. Although generally well tolerated, PRRT may precipitate or exacerbate pre-existing hormonal syndromes in patients with functioning NETs, leading to acute endocrine decompensation requiring urgent management. Current recommendations from the most important NET societies for prevention and treatment remain inconsistent, and available evidence is still fragmented. To address this gap, we conducted a comprehensive systematic review of the literature in PubMed, Scopus, and Embase up to May 2025, with the aim of identifying, organizing, and critically appraising the existing evidence on prevention and therapeutic strategies for managing hormonal crises in patients undergoing PRRT. Twenty-eight studies were included, comprising 18 case reports/series, 7 retrospective studies, and 3 prospective studies. Reported events included carcinoid crisis, insulinoma-related hypoglycemia, VIPoma-related secretory crisis, ectopic Cushing syndrome exacerbation, and catecholaminergic crisis in pheochromocytoma/paraganglioma. Carcinoid crisis was the most frequently reported endocrine emergency, with available cohort studies suggesting an incidence ∼1% during PRRT, although definitions and reporting remain heterogeneous. Hypoglycemic crises occurred mainly during the first PRRT cycle in patients with insulinoma, supporting the role of inpatient monitoring and preventive glucose-stabilizing strategies. Evidence for rarer syndromes was limited to small series and case reports but consistently emphasized pretreatment endocrine optimization, syndrome-specific prophylaxis, early recognition, and multidisciplinary management. Overall, available data remain insufficient to support firm recommendations but suggest that structured risk assessment, periprocedural monitoring, and harmonized management algorithms are essential to improve PRRT safety in functioning NETs.

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Cite

BibTeXRIS
BibTeX
@article{arrivi2026prevention,
  title = {{Prevention and management of hormonal crisis in neuroendocrine tumors undergoing PRRT (peptide receptor radionuclide therapy): a systematic review.}},
  author = {G Arrivi and M Pagnanelli and G Puliani and A Zerbi and S Partelli and F Panzuto},
  journal = {ESMO gastrointestinal oncology},
  year = {2026},
  month = oct,
  doi = {10.1016/j.esmogo.2026.100428},
  url = {https://europepmc.org/article/MED/42927326},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Prevention and management of hormonal crisis in neuroendocrine tumors undergoing PRRT (peptide receptor radionuclide therapy): a systematic review.
AU  - G Arrivi
AU  - M Pagnanelli
AU  - G Puliani
AU  - A Zerbi
AU  - S Partelli
AU  - F Panzuto
PY  - 2026
DA  - 2026/10/17
JO  - ESMO gastrointestinal oncology
DO  - 10.1016/j.esmogo.2026.100428
UR  - https://europepmc.org/article/MED/42927326
AB  - Peptide receptor radionuclide therapy (PRRT) is an established treatment of advanced well-differentiated neuroendocrine tumors (NETs) expressing somatostatin receptors. Although generally well tolerated, PRRT may precipitate or exacerbate pre-existing hormonal syndromes in patients with functioning NETs, leading to acute endocrine decompensation requiring urgent management. Current recommendations from the most important NET societies for prevention and treatment remain inconsistent, and available evidence is still fragmented. To address this gap, we conducted a comprehensive systematic review of the literature in PubMed, Scopus, and Embase up to May 2025, with the aim of identifying, organizing, and critically appraising the existing evidence on prevention and therapeutic strategies for managing hormonal crises in patients undergoing PRRT. Twenty-eight studies were included, comprising 18 case reports/series, 7 retrospective studies, and 3 prospective studies. Reported events included carcinoid crisis, insulinoma-related hypoglycemia, VIPoma-related secretory crisis, ectopic Cushing syndrome exacerbation, and catecholaminergic crisis in pheochromocytoma/paraganglioma. Carcinoid crisis was the most frequently reported endocrine emergency, with available cohort studies suggesting an incidence ∼1% during PRRT, although definitions and reporting remain heterogeneous. Hypoglycemic crises occurred mainly during the first PRRT cycle in patients with insulinoma, supporting the role of inpatient monitoring and preventive glucose-stabilizing strategies. Evidence for rarer syndromes was limited to small series and case reports but consistently emphasized pretreatment endocrine optimization, syndrome-specific prophylaxis, early recognition, and multidisciplinary management. Overall, available data remain insufficient to support firm recommendations but suggest that structured risk assessment, periprocedural monitoring, and harmonized management algorithms are essential to improve PRRT safety in functioning NETs.
SN  - 2949-8198
ER  -