Insulinoma

Question 1

Insulinoma

Answer 1

Insulinoma

An insulinoma is a neuroendocrine tumour deriving mainly from pancreatic Islets of Langerhans cells

Basics
most common pancreatic endocrine tumour
10% malignant, 10% multiple
of patients with multiple tumours, 50% have MEN-1

Features
of hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc
rapid weight gain may be seen
high insulin, raised proinsulin:insulin ratio
high C-peptide

Diagnosis
supervised, prolonged fasting (up to 72 hours)
CT pancreas

Management
surgery
diazoxide and somatostatin if patients are not candidates for surgery

Question 2

Endogenous insulin vs Exogenous insulin - Example Question

Answer 2

A 24 year old student nurse is brought to the Emergency Department having collapsed at work. Apart from depression for which she takes sertraline, she has no other past medical history. This is her third collapse in a month. On each attendance capillary blood glucose measurements have been < 4mmol/L. An oral glucose tolerance test performed two weeks previously by her GP was normal.

Today:

C-peptide 3.9ng/ml (0.8 - 3.1ng/ml)
Glucose 3.4mmol/L

What is the most appropriate next investigation?

	Early morning C-peptide levels
	Toxicology screen
	CT scan of pancreas
	No further investigations, advise her to stop self-administering insulin
	> 72 hour fast

The key to this question is the recognition that C - peptide is increased by endogenous insulin and suppressed by exogenous insulin. Therefore it is likely that this patient has an excess of endogenous insulin ie. insulinoma.

The gold standard investigation for an insulinoma is the 72 hour fast during which C - peptide and insulin levels are measured. The tumour may be too small to be seen on CT and therefore endoscopic ultrasound is the preferable investigation if the diagnosis is still suspected despite a normal fast.

Question 3

Sulfonylurea Abuse vs Insulinoma - Example Question

Answer 3

A 20-year-old nurse with no past medical history presents following a collapse with a blood sugar 1.5 mmol/l . You phone her general practitioner and find out she has had 6 month history of episodes hypoglycemia. The cause has not been established and she is awaiting an outpatient endocrinology opinion. In hospital her bloods come back showing an insulin level 350 mIU/L(18-276) 1 hour after lunch. Her C-peptide level at this time is 3.50 ng/ml (0.51 to 2.72). Her TSH is 0.03 mIU/L . What test should be performed next?

	Urgent MRI pancreas
	Urgent ultrasound thyroid
	Urgent MRI head
	> Urine or serum sulphonylurea levels
	Short Synacthen test

Sulphonylureas increase the release of pro-insulin and hence give a similar biochemical picture to an insulinoma. The co-existing low TSH in a young female patient with access to hospital drugs raises the possibility of exogenous medication use. Testing the patients urine or serum for sulphonylurea levels would be an easy, low cost and simple test prior to further work up.
The levels would obviously be zero in a patient with an insulinoma. In patients illicitly taking exogenous insulin one would expect high insulin levels but low C-peptide levels.

Question 4

Insulinoma - Always remember to exclude MEN 1

Answer 4

50% of patients with multiple pancreatic endocrine tumours and consequent insulinoma have MEN Type 1

How to exclude:

• Exclude hyperprolactinaemia due to pituitary adenoma
• Exclude hyperparathyroidism due to parathyroid hyperplasia
• Exclude hypergastrinaemia due to gastronoma

Question 5

Supervised Prolonged Fasting in Insulinoma

Answer 5

Diagnostic of Insulinoma:

• Serum insulin levels of 10microU/mL or more (Normal <6microU/mL)
• Glucose < 40mg/dL
• C-peptide levels exceeding 2.5ng/mL (Normal <2ng/mL)
• Proinsulin levels >= 22pmol/L or >25% that of immunoreactive insulin

(+ Screening for sulfonylurea negative)

Question 6

C-peptide, Endogenous Insulin and Exogenous Insulin

Answer 6

THE KEY = the recognition that C - peptide is increased by endogenous insulin and suppressed by exogenous insulin.

THEREFORE
Insulinoma = High C peptide, Low Glucose, High Pro-insulin
Sulfonylurea abuse = has same picture ! Need urine or serum sulfonylurea screen to differentiate

Insulin Abuse = Low C-Peptide, Low Glucose