AKT · Endocrine/Paraneoplastic & neuroendocrinelow yield

Insulinoma

Insulin-secreting pancreatic neuroendocrine tumour

Overview

An insulin-secreting pancreatic neuroendocrine tumour — the commonest functioning pancreatic NET. Causes fasting/exertional HYPOGLYCAEMIA with Whipple's triad. Diagnosed by inappropriately high insulin and C-peptide during hypoglycaemia (with low ketones); usually benign and resected. Part of MEN1 in a minority.

Recognise

Recurrent HYPOGLYCAEMIA on fasting/exertion: confusion, sweating, palpitations, tremor, seizures, relieved by glucose (Whipple's triad)
Weight gain (frequent eating to avoid hypos); symptoms often misattributed to neurological/psychiatric illness
Inappropriately high INSULIN and C-PEPTIDE during documented hypoglycaemia, with suppressed ketones

Red flags

Severe neuroglycopenia (seizures, coma)
MEN1 association → screen for hyperparathyroidism/pituitary tumours

Differentials & how to tell them apart

Exogenous insulin (factitious)high insulin but SUPPRESSED C-peptide (exogenous insulin has no C-peptide)

Sulfonylurea-induced hypoglycaemiahigh insulin AND C-peptide — but sulfonylurea detected on the drug screen

Non-islet-cell tumour hypoglycaemiaIGF-2-secreting tumour — low insulin/C-peptide

Investigations

Supervised 72-h fast: hypoglycaemia with raised insulin + C-PEPTIDE + proinsulin and LOW ketones; sulfonylurea screen (exclude). Localise (CT/MRI/EUS, somatostatin scan). Screen for MEN1.

Management

Surgical resection (diazoxide/octreotide to control hypoglycaemia pre-op)

1Confirm endogenous hyperinsulinaemic hypoglycaemia (raised insulin + C-peptide + proinsulin, low ketones, negative sulfonylurea screen) during a supervised fast; localise. Resect the tumour.Gate: C-PEPTIDE separates the causes: HIGH in insulinoma/sulfonylurea (endogenous insulin), SUPPRESSED with exogenous (factitious) insulin — and a sulfonylurea screen catches the drug cause; screen for MEN1
2Surgical enucleation (usually curative); diazoxide/somatostatin analogue/everolimus for unresectable disease; MEN1 surveillance.

Surgical resection (enucleation) — curative for benign localised tumours

Diazoxide / somatostatin analogue — control hypoglycaemia while awaiting surgery or if unresectable

Key points

Fasting hypoglycaemia + high insulin + high C-peptide + low ketones = insulinoma. C-peptide is the key: high (endogenous) vs suppressed (exogenous insulin); the sulfonylurea screen excludes the drug. Think MEN1.

Monitor & prognosis

Glucose; MEN1 screening.

Excellent (mostly benign, resectable).

Source: ENETS/UKINETS; StatPearls