Gastroenteropancreatic neuroendocrine neoplasms: A clinical snapshot

Table 2 Clinical features, incidence, cancer risk, multiple endocrine neoplasia 1 association, and treatment of various functional pancreatic neuroendocrine neoplasms[29-32]

Name of f-pNENs	Proportion of f-NENs	Incidence million/year	Biomarker	Location of the NENs	Malignancy (proportion)	MEN1 association	Symptoms, signs, and laboratory testing features	Surgery: Indication and procedure
Insulinoma	30%-40%	1-32	Insulin	Pancreas: > 99%	< 10%	4%-5%	Hypoglycemia symptoms Whipple’s triad, weight gain. ↑Insulin, ↑proinsulin levels. ↑C-peptide on 72 h fast test	Always. Parenchymal sparing pancreatectomy
Gastrinoma ZES	16%-30%	0.5-21.5	Gastrin	Duodenum: 70%. Pancreas: 25%. Others: 5%	60%-90%	20%-25%	Complicated or difficult to treat PUD, GORD, profuse diarrhoea. ↑Gastrin levels, ↓Gastric pH. Secretin stimulation test	Yes, except < 2 cm MEN1/ZES. Standard pancreatectomy
VIPoma or WDHA Verner-Morrison syndrome. Pancreatic cholera	< 10%	0.05-0.2	VIP	Pancreas: 90% Neural, adrenal, preganglionic: 10%	40%-70%	6%	Profuse watery diarrhoea, hypokalaemia, metabolic acidosis, achlorhydria, and dehydration; ↑VIP levels	Yes. Standard pancreatectomy
Glucagonoma	< 10%	0.01-0.1	Glucagon	Pancreas: 100%	50%-80%	1%-20%	Rash (necrolytic migratory erythema), weight loss, new onset diabetes mellitus and thromboembolic events. ↑Glucagon levels	Yes. Standard pancreatectomy
Somatostatinoma	< 5%	Rare	Somatostatin	Pancreas 55% Duodenum-jejunum: 44%	> 70%	45%	New onset diabetes, gallstones, weight loss, diarrhoea, steatorrhoea, ↑Somatostatin	Yes. Standard pancreatectomy
GRHoma	Rare	Unknown	GHRH	Pancreas: 30%, Lung 54%, Jejunum: 7%, and Others: 13%	> 60%	16%	Acromegaly with/without peptic ulcer, wheeze, flushing, renal stone, ↑GHRH levels	Yes. Standard pancreatectomy
ACTHoma	Rare	Rare	ACTH	Pancreas	> 95%	Rare	Ectopic Cushing’s syndrome. 4%-16% of all ectopic Cushing	Yes. Standard pancreatectomy
PTHrP-oma	Rare	Rare	PTHrP	Pancreas	84%	Rare	Rare cause of hypercalcemia. Pain abdomen: Liver metastasis	Yes. Standard pancreatectomy
Carcinoid syndrome arising from pNEN	Rare	Rare	Serotonin Tachykinin?	Pancreas: < 1% of all carcinoid syndrome	60%-88%	Rare	Flushing, diarrhoea, broncho-spasm, carcinoid heart disease↑ urinary 5-HIAA levels	Yes. Standard pancreatectomy

NENs: Neuroendocrine neoplasms; pNENs: Pancreatic NENs; f-pNENs: Functional-pNENs; MEN1: Multiple endocrine neoplasia 1; 5-HIAA: 5-hydroxy indole acetic acid; ZES: Zollinger Ellison syndrome; PVD: Peripheral vascular disease; GORD: Gastro-oesophageal reflux disease; WDHA: Watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria; VIP: Vasoactive intestinal peptide; GHRH: Growth hormone releasing hormone; PTHrP: Parathyroid hormone-related peptide; GRHomas: GHRH secreting pNENs; ACTH: Gastrin, somatostatin, adrenocorticotropin.