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Insulinoma

An insulinoma is a tumour of the pancreas derived from the beta cells which while retaining the ability to synthesize and secrete insulin is autonomous of the normal feedback mechanisms. Patients present with symptomatic hypoglycemia which is ameliorated by feeding. The diagnosis of an insulinoma is usually made biochemically with low blood sugar, elevated insulin, pro-insulin and C-peptide levels and confirmed by medical imaging or angiography. The definitive treatment is surgery. more...

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Features

Insulinomas are rare neuroendocrine tumours with an incidence of 4 in 5 million. They account for 60% of tumours arising from the islets of Langerhans cells. Eighty percent of these tumours are solitary and benign. In 10%, they are malignant (with metastases) and the remainder are multiple tumours. Over 99% of insulinomas are found in the pancreas, with rare cases in ectopic pancreatic tissue. About 5% of cases are associated with tumours of the parathyroid glands and the pituitary (Multiple endocrine neoplasia type 1) and are more likely to be multiple and malignant. Most insulinomas are small, less than 2 cm.

Signs and Symptoms

Patients with insulinomas usually develop neuroglycopenic symptoms. These include recurrent headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and permanent neurological damage. Symptoms resulting from the catecholinergic response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia, sweating, hunger, anxiety, nausea) are not as common.

Diagnosis

The diagnosis of insulinoma is suspected in a patient with symptomatic fasting hypoglycemia. The conditions of Whipple’s triad need to be met for the diagnosis of hypoglycemia to be made:

1. symptoms and signs of hypoglycemia,

2. concomitant plasma glucose level of 45 mg/dL (2.5 mmol/L) or less, and

3. reversibility of symptoms with administration of glucose.

Blood tests

The following blood tests are needed to diagnose insulinoma:

glucose
insulin
C-peptide

If available, a proinsulin level might be useful as well. Other blood tests may help rule out other conditions which can cause hypoglycemia.

Suppression tests

Normally, endogenous insulin production is suppressed in the setting of hypoglycemia. A 72-hour fast, usually supervised in a hospital setting, can be done to see if insulin levels fail to suppress, which is a strong indicator of the presence of an insulin-secreting tumour.

During the test, the patient may have calorie-free and caffeine-free liquids. Capillary blood glucose is measured every 4 hours using a reflectance meter, until values < 60 mg/dL (3.3 mmol/L) are obtained. Then, the frequency of blood glucose measurement is increased to every hour until values are < 49 mg/dL (2.7 mmol/L). At that point, or when the patient has symptoms of hypoglycemia, a blood test is drawn for serum glucose, insulin, proinsulin, and C-peptide levels. The fast is stopped at that point, and the hypoglycemia treated with intravenous dextrose or calorie-containing food or drink.

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GlucaGen® HypoKit : an important consideration for all patients treated with insulin - glucagon rys
From Diabetes and Primary Care, 6/22/02

Many patients treated with insulin will experience severe hypoglycaemia at some time; yet relatively few have glucagon on hand. This is despite the fact that severe hypoglycaemia is considered to be a major cause of anxiety amongst insulin-treated patients. (1)

Causes of hypoglycaemia include skipping meals, stress, taking too much exercise or drinking too much alcohol. However, perhaps a more troubling cause is linked to intensive insulin therapy.

The risk of a severe hypoglycaemic event is 2-3 times higher in patients aiming to achieve optimal glucose control with intensive insulin therapy. (2) The fear of hypoglycaemia may inhibit patients from maintaining tight control of their blood sugar, thus depriving them of the key benefits intensive control offers, i.e. significant delay or prevention of long-term complications.

Healthcare professionals dealing with diabetes patients on a regular basis will be well attuned to the fear their patients have about hypoglycaemia. It is therefore important that glucagon administration is included as part of patient education programmes. Glucagon should be considered as a way of helping patients overcome their anxiety surrounding hypoglycaemia and become as expert as possible in achieving optimal control over their diabetes. Healthcare professionals can play a key role in ensuring that all patients and their relatives receive adequate training on hypoglycaemia and the use of glucagon.

The Novo Nordisk GlucaGen HypoKit provides a user friendly means of administering glucagon. For further information please call the Novo Nordisk Customer Care Line 0845 600 5055. (calls are charged at local rates and may be monitored for training purposes)

(1.) Pramming S. Thorsteinsson B. Bendtson I. Binder C. Diab Med 1991, 8: 217-222

(2.) DCCT Research Group. N Engl J Med 1993, 329: 977-86

(Prescribing information for GlucaGen HypoKit is on p. 3)

RELATED ARTICLE: ABBREVIATED PRESCRIBING INFORMATION FOR GLUCAGEN HYPOKIT 1MG

GlucaGen HypoKit 1mg Glucagon (rys)

Presentation: A vial containing 1mg (1 iu) glucagon (rys), as the hydrochloride, and lactose 107mg, together with a pre-filled syringe containing 1 ml Water for injections.

Uses: The treatment of severe hypoglycaemic reactions which may occur in the management of diabetic patients receiving insulin. As a motility inhibitor in examinations of the gastrointestinal tract. As a motility inhibitor in CT, NMR and DSA.

Dosage: The glucagon is dissolved in the accompanying diluent before use.

Treatment of severe hypoglycaemic reactions: 1mg (adults, children above 25kg or 6 - 8 years) or 0.5mg (children below 25kg or 6 - 8 years) by subcutaneous, intramuscular, or intravenous injection. When the patient responds, administer oral carbohydrate. If no response within 10 minutes, give intravenous glucose.

Diagnostic indications: Doses range from 0.1-2mg depending on the diagnostic technique used and the rank of administration. Usual dose for relaxation of stomach. duodenal bulb, duodenum and small bowel is 0.2-0.5mg i.v. or 1mg i.m. To relax the colon 0.5-0.75mg iv. or 2mg i.m. In CT, NMR and OSA doses up to 1mg i.v. are used.

Contra-indications: Phaeochromocytoma. Hypersensitivity to glucagon or excipients. Do not use if solution contains particles, or has viscous appearance.

Precautions: Glucagon reacts antagonistically towards insulin. Observe caution in patients with insulinoma or glucagonoma, and in diabetics or elderly patients with known cardiovascular disease.

Use in pregnancy: Glucagon does not cross the placenta. Glucagon has been used in pregnant diabetics; no harmful effects known with respect to course of pregnancy or health of foetus and neonate.

Side effects: Occasionally nausea and vomiting, which tends to be dose related. Positive inotropic and chronotropic effects (tachycardia). Rarely hypersensitivity.

PL numbers: GlucaGen 1mg PL 4668/0027

Diluent for GlucaGen 1mg fsyhnge) PL 4666/0026

Legal category: POM

Basic NHS price: GlucaGen HypoKit 1mg [pounds sterling]19.95 Full prescribing information can be obtained from: Novo Nordisk Limited, Broadfield Park, Brighton Road, Crawley, West Sussex RH 11 9RT. Tel: (01293) 613555

Date of Preparation: May 2002

HOW TO ADMINISTER GLUCAGEN: A STEP-BY-STEP GUIDE

1. Insert the needle through the rubber disk of the GlucaGen bottle and inject all of the contents of the syringe into the bottle.

2. Without withdrawing the syringe, gently shake the bottle until the GlucGen is completely dissolved.

3. Ensure that the plunger is first fully depressed. Then draw up the entire solution into the syringe.

4. Ensure there is no air remaining in the syringe before giving the injection. When the patient responds, give them a sweet drink or snack to prevent a further hypo.

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