Insulinoma

This diagnosis relates to an insulin secreting tumour of the pancreas. This section also covers the investigation of spontaneous hypoglycaemia of any cause.

Suspected reactive hypoglycaemia


History

Lack of weight gain, long standing symptoms and a clear relationship to meals are suggestive of reactive hypoglycaemia.


Arrange prolonged OGTT

If there is a normal response to OGTT, reassure patient.  


Reactive hypoglycaemia confirmed

If reactive hypoglycaemia is evident on the glucose tolerance test, and insulinoma is not suspected clinically, reassure the patient, arrange dietetic review and give simple advice on eating low glycaemic index foods to minimise symptoms. Severe symptoms may also improve with the alpha glucosidase inhibitor acarbose. Guar gum may also prevent symptoms in some people.

History suggestive of insulinoma or any documented hypoglycaemia


History

A history of weight gain, a short history of typical attacks, a family history suggestive of MEN1, or documented hypoglycaemia are all highly suggestive and mandate admission for a formal fast.


Formal 48-72hr fast

Fast should be terminated at any stage if the patient develops severe symptoms, such as loss of consciousness or fitting, or if urgent laboratory analysis confirms serum glucose <2.2mmol/l. 

Plasma should be sent for insulin and C peptide measurement as per protocol LINK, and paired blood and spot urine samples also sent for sulphonylurea screen.


Interpreting results

Normal young women may run blood glucose levels as low as 2.2-3mmol/l. True hypoglycaemia (<2.2mmol/l) should be accompanied by very low insulin and C peptide levels.

Factitious insulin use should be suspected if low C peptide is found with a detectable insulin level. It may be necessary for further analysis to be performed to detect insulin analogues in the serum in difficult cases. 

Elevated C peptide and insulin in the presence of hypoglycaemia indicates possible insulinoma, although sulphonylurea screen must also be performed at this stage.


Start treatment

With biochemically confirmed hypoglycaemia, the fast must be terminated immediately. Emergency glucose administration should also be given, intravenously if necessary, and treatment with diazoxide is usually started.


Diazoxide

This is the first line of treatment. The dose should be uptitrated every 24-48hr to achieve normoglycaemia, although the patient needs to be warned about possible side effects including oedema, hypertrichosis and hypokalaemia.


Intravenous glucose infusion

This may be necessary in severe cases while oral treatments are uptitrated.


Steroids

Oral prednisolone may be added to diazoxide if necessary. Hypoglycaemia may respond to this, at least transiently.


Somatostatin analogues

These may reduce peptide hormone release in neuroendocrine tumours and will usually improve diarrhoea and flushing. This treatment may be considered in insulinoma not responding to standard treatments.


Arrange localising studies and complete baseline investigations

CT pancreas is the usual first line investigation after biochemical diagnosis. If the lesion is not clear with this modality, trans abdominal and endoscopic ultrasound scans may be performed. Selective venous sampling with calcium stimulation should also be considered.

If malignant insulinoma is suspected, or if no lesion is detected with conventional means, consider octreotide and MIBG scanning.

At confirmation of biochemical diagnois, also arrange fasting gut hormones (using intravenous glucose to maintain safe blood glucose levels during the 12 hour fast), calcium, parathyroid hormone level and baseline pituitary function.


Discuss results at multidisciplinary meeting and arrange surgery

Selective pancreatic surgery is usually possible.


Post operative management

Stop all treatments immediately post operatively and closely monitor blood glucose levels.


Follow up arrangements

Arrange formal post operative review at six weeks, then on an annual basis.

Annual screens should include: reassessment of family history, full blood count, urea and electrolytes, liver function test, bone profile, prolactin, fasting glucose and HbA1c. 

The decision on repeat imaging of the pancreas should be determined by multidisciplinary discussion.


All patients with confirmed MEN1 should be followed up accordingly

At diagnosis of MEN1, discuss genetic counselling and family screening and arrange appropriate life long follow up.