Gastroenteropancreatic neuroendocrine tumors in 2025: From molecular profiling to artificial intelligence-driven therapy

Table 1 Clinical manifestations and diagnostic considerations of gastroenteropancreatic neuroendocrine tumors

Tumor type/syndrome	Hormone secreted	Key clinical manifestations	Diagnostic pearls and challenges	Ref.
Insulinoma	Insulin	Fasting hypoglycemia, neuroglycopenic symptoms (confusion, seizures), autonomic symptoms (tremor, diaphoresis), weight gain	Symptoms relieved by glucose intake; tumors often small; diagnosis frequently delayed	[40,43]
Glucagonoma	Glucagon	Weight loss, diabetes mellitus, necrolytic migratory erythema, diarrhea, stomatitis	Dermatologic findings may precede diagnosis; often metastatic at presentation	[42,45,46]
Somatostatinoma	Somatostatin	Diabetes mellitus, steatorrhea, cholelithiasis, hypochlorhydria, weight loss	Subtle or incomplete syndrome; diagnosis commonly incidental	[43,44]
PPoma	Pancreatic polypeptide	Nonspecific symptoms, abdominal discomfort, weight loss; mass-effect manifestations	Lacks a distinctive hormonal syndrome; frequently associated with MEN1	[45,49]
Carcinoid syndrome	Serotonin	Episodic flushing, secretory diarrhea, bronchospasm, right-sided heart disease, pellagra	Typically requires hepatic metastases; cardiac involvement impacts prognosis	[58-60]
Zollinger-Ellison syndrome	Gastrin	Refractory peptic ulcers, severe GERD, chronic diarrhea	MEN1 association; hypergastrinemia-driven acid hypersecretion	[59-62]
Nonfunctional NETs	None	Abdominal pain, jaundice, obstruction, constitutional symptoms	Frequently advanced at diagnosis; symptoms reflect tumor burden	[40,63-65]
Bone metastases		Localized bone pain, pathological fractures	Marker of advanced systemic disease	[67-71]

NET: Neuroendocrine tumor; GERD: Gastroesophageal reflux disease; MEN1: Multiple endocrine neoplasia type 1.