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J R Soc Med. 2001 July; 94(7): 349–350.
PMCID: PMC1281602

Difficult insulinoma

J M Lawrence, BSc MRCP, T Smith, BM MRCP, D Iles, BSc MRCP, and J P D Reckless, MD FRCP

Immediate management of insulinoma can be extremely troublesome. For resistant hypoglycaemic episodes, glucagon can be useful pending more definitive treatment.

CASE HISTORY

A man aged 61 was seen in accident and emergency with reduced consciousness (Glasgow Coma Scale score 11/15) and a dense right hemiplegia. The provisional diagnosis was a left-sided cerebrovascular accident. However, near-patient glucose testing suggested hypoglycaemia and a laboratory glucose was 1.2 mmol/L. Symptoms resolved in 5-10 minutes with intravenous dextrose. Plasma insulin (47 mU/L) and C-peptide (2903 pmol/L [normal 120-600]) were high. On direct questioning he and his wife said that, for the past few days, he had been confused and disoriented before breakfast, recovering after food. A computed tomographic (CT) scan revealed multiple liver and spleen deposits, and an ultrasound-guided liver biopsy showed a poorly differentiated neuroendocrine tumour. This was judged inoperable. He continued to experience recurrent episodes of hypoglycaemia with associated disorientation and impaired consciousness. Increasingly large volumes of 10-20% dextrose were required to limit these episodes, with associated fluid overload and hyponatraemia. Oral high-dose diazoxide (200 mg three times daily) was ineffective and exacerbated the fluid overload. Subcutaneous octreotide (in doses up to 200 μg three times daily) increased rather than decreased the frequency and severity of hypoglycaemia. Intravenous glucagon infusion at up to 4 mg/h stopped the hypoglycaemic episodes and he was discharged home on a subcutaneous glucagon infusion, 2 mg/h. He was then treated with streptozotocin (three courses of 5 days of 1000 mg/day and two courses of 5 days of 750 mg/day over six months in total) and 5-fluorouracil (two courses of 5 days of 1000 mg/day, one course of 5 days of 800 mg/day and two courses of 5 days of 750 mg/day over 6 months). As chemotherapy was initiated, glucagon was withdrawn over 10 days. There were no further episodes of hypoglycaemia and 12 months from the original presentation the patient is symptom-free.

COMMENT

Insulinoma is the commonest hormone-secreting pancreatic tumour. 10% are malignant. Although usually sporadic, insulinomas are the commonest of the pancreatic tumours that may occur in families with multiple endocrine neoplasia 1 (MEN-1). Symptoms tend to be intermittent, with episodes of disorientation, confusion or behaviour change, and the diagnosis is commonly delayed for months or years. When complete surgical resection is impossible, debulking procedures, tumour embolization and chemotherapy can reduce episodes of hypoglycaemia.

Initial management of insulinoma centres on relieving episodes of hypoglycaemia with dextrose, but the large volumes can result, as here, in fluid overload. Diazoxide can be of short and long term value1. It binds to the same receptor on the pancreatic β-cell as sulphonylureas but has the opposite effect, inhibiting insulin release. Poorly differentiated tumours may not respond, possibly because they lack sulphonylurea receptors. Octreotide, a long-acting somatostatin analogue, has a wide range of effects including inhibition of insulin, growth hormone and glucagon secretion. Variable expression of these receptor subtypes in insulinomas explains why some patients benefit in terms of hypoglycaemia while others even get worse.2,3. A trial of octreotide with serial blood glucose estimations can be helpful.

Glucagon stimulates gluconeogenesis and glycogenolysis and can be useful in insulinoma patients whose liver glycogen stores are replete. In previous reports it was given as a continuous intravenous infusion via a central line4,5. Subcutaneous glucagon is easier to manage and was highly effective in our patient, allowing early discharge while chemotherapy continued. It is expensive (1 mg costs £12.95) but should be considered where other treatments have failed.

References

1. Gill GV, Rauf O, Macfarlane IA. Diazoxide treatment for insulinoma: a national UK survey. Postgrad Med J 1997;73: 640-1 [PMC free article] [PubMed]
2. Barrons RW. Octreotide in hyperinsulinism. Ann Pharmacother 1997;31: 239-41 [PubMed]
3. Gama R, Marks V, Wright J, Teale JD. Octreotide exacerbated fasting hypoglycaemia in a patient with a proinsulinoma; the glucostatic importance of pancreatic glucagon. Clin Endocrinol 1995;43: 117-20 [PubMed]
4. Hoff AO, Vassilopoulou-Sellin R. The role of glucagon administration in the diagnosis and treatment of patients with tumour hypoglycemia. Cancer 1998;82: 1585-92 [PubMed]
5. Samaan NA, Pham FK, Sellin RV, Fernandez JF, Benjamin RS. Successful treatment of hypoglycemia using glucagon in a patient with extrapancreatic tumour. Ann Intern Med 1990;113: 404-6 [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press