25th May 2025

Insulinoma

Insulinomas are insulin secreting tumours of the pancreas. This arises from APUD cells in the islets of Langerhans cells.  They typically present with hypoglycaemia from the endogenous production of insulin and these tend to occur during fasting or exercise. Around 20% of patients develop symptoms postprandially.  Whilst most tumours are benign, around 10% occur as part of MEN.

Differentiating between other causes of hypoglycaemia is important here. Differentials include exogenous insulin use and sulphonylurea use.

Investigations

Bloods in insulinoma should show: 

• Symptomatic hypoglycaemia <3.0mmol/L
• Insulin > 3.0uU/mL
• C-peptide > 0.6ng/mL
• Proinsulin ≥ 5 pmol/L

C-peptide is released when endogenous proinsulin is broken down into insulin. Therefore this will be raised only with endogenous insulin production and not with injectable/exogenous insulin use. Sulphonylureas (eg gliclazide) will cause the body to make insulin so this will also release C-peptide.

The below table summarises the interpretation of blood tests in determining the cause of hypoglycaemia. 

Table 1: interpreting blood test results in hypoglycaemia

To determine between insulinoma and sulphonylurea use (factitious hypoglycaemia) we can test for serum proinsulin levels (which would be significantly raised in insulinoma due to excess insulin production) or for serum or urine sulphonylurea.   

48-72 hour supervised fast: 

• in insulinoma this will invoke hypoglycaemia at which point the test stops
• Glucose, C-peptide and insulin levels should be sent off once hypoglycaemic

MRI/CT imaging

Endoscopic ultrasound if no visible lesion on imaging

GLP-1 receptor imaging (nuclear medicine scan specific for insulinoma)

Management

Management of hypoglycaemia: 

• Dietary, diazoxide – a drug which inhibits insulin secretion, octreotide to normalise blood glucose
• Definitive management:
  • Resectable disease: Laparoscopic (for small, single lesions), partial pancreatectomy, radical resection. Based on location and size of lesion. 
  • Unresectable disease (if high risk, metastatic disease): radiofrequency ablation, embolization, intra-arterial chemotherapy – depending on patient factors and MDT decision