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

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.