Hypoglycaemia

Hypoglycaemia¹ is defined as blood glucose <3.0mmol/l but less than 2.5mmol/l is considered pathological, requiring investigation.

The diagnosis of hypoglycaemia rests on three criteria (Whipple's triad) of plasma hypoglycaemia, symptoms attributable to a low blood sugar level and resolution of symptoms with correction of the hypoglycaemia.

There are many causes of hypoglycaemia, but it is most commonly the result of an excess of either insulin or oral hypoglycaemic medications combined with reduced sugar intake or increased activity.

• If insulin and C-peptide levels are elevated an endogenous insulin source is the cause
• This can result from either an insulinoma, sulfonylurea drug (which stimulates the pancreatic islet cells to release insulin), drugs with a sulfonylurea-like action (e.g. quinine), extrapancreatic IGF-II secreting neoplasms, e.g. adrenal tumour or autoimmune hypoglycaemia.

Insulinomas

• Insulinomas usually cause semiautonomous release of insulin, resulting in fasting hypoglycaemia
• In response to meals these tumours usually respond subnormally, so that postprandial glucose levels are normal or even mildly elevated, although postprandial hypoglycaemia can occur.
• Insulinomas may be too small to be seen on CT scans and further investigation with endoscopic ultrasound should be considered, if no other cause for the hypoglycaemia is apparent.
• Glucagon should be used with caution in insulinoma.

Sulfonylurea Overdose

• Sulfonylurea overdose can lead to profound hypoglycaemia, with chlorpropamide and glibenclamide being the agents most frequently implicated
• Both prolonged and recurrent hypoglycaemia must be expected. Potassium supplementation is often required.
• Dextrose infusions are usually sufficient, but can stimulate further insulin release from the sulfonylurea-primed beta cells
• Octreotide and diazoxide both inhibit insulin release and have been recommended for treating severe poisoning refractory to dextrose
• Steroids and glucagon have also been recommended, but are thought to be less effective

Other causes include drugs and toxins including pentamidine, paracetamol and toadstools. Alcohol is the commonest non-iatrogenic cause of hypoglycaemia.

This is a common problem with diabetes the most common risk factor.

There is poor correlation between blood glucose and symptoms, especially in diabetic patients.² Patients can often recognise the symptoms themselves and this state responds to sugar in water or a few lumps of sugar. Children may not have such prominent changes but may appear unduly lethargic.
Hypoglycaemia presents as:

• Shaking and trembling
• Sweating, pins and needles in lips and tongue
• Hunger, palpitations
• Headache (occasionally), double vision, difficulty in concentrating
• Slurring of speech, confusion, change of behaviour, truculence
• Stupor, coma

Subacute Hypoglycaemia

• Also known as hypoglycaemia unawareness. Is seen in IDDM patients who may show reduction in spontaneous movements and speech, somnolence, poor thinking and work performance, changes in personality and amnesia. It may also present with transient hemiplegia, hypo-or hyperthermia, convulsions, diplopia and strabismus.³ If untreated can progress to stupor, coma and exceptionally death.
• Chronic – a rare presentation with insidious changes in personality, defects in memory, paranoia, apparent dementia. Can also appear as neuropathy mistaken for motorneurone disease.

In Adults⁴

• Initially glucose 10-20 g is given by mouth either in liquid form or as granulated sugar or sugar lumps
• Glucose 10 g is available from 2 teaspoons sugar, 3 sugar lumps, GlucoGel™- formerly known as Hypostop™ Gel; glucose 9.2 g/23-g oral ampoule, available from British BioCell International; milk 200 ml; and non-diet versions of Lucozade™ Sparkling Glucose Drink 50-55 ml, Coca-Cola™ 90 ml, Ribena™ Original 15 ml (to be diluted).
• If necessary this may be repeated in 10-15 minutes.

For further management see Emergency Treatment of Hypoglycaemia.

In Children⁵

• Prompt treatment of hypoglycaemia in children from any cause is essential to prevent subsequent neurological damage.
• Hyperinsulinism, fatty acid oxidation disorders and glycogen storage disease are less common causes of acute hypoglycaemia in children.
• Hypoglycaemia which causes unconsciousness or fitting is an emergency.

Neonatal Hypoglycaemia

This is a relatively common problem. Prompt feeding may be all that is required. If, however, this is not possible:

• Neonatal hypoglycaemia is treated with glucose intravenous infusion 10% given at a rate of 5 ml/kg/hour.
• An initial dose of 2.5 ml/kg over 5 minutes may be required if hypoglycaemia is severe enough to cause loss of consciousness or fitting.
• Mild asymptomatic persistent hypoglycaemia may respond to a single dose of glucagon.
• Dose is 20mcg per kg.

Glucagon has also been used in the short-term management of endogenous hyperinsulinism.

Diazoxide, administered by mouth, is useful in the management of children with chronic hypoglycaemia from excess endogenous insulin secretion, either from an islet cell tumour, islet cell hyperplasia or persisting hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis).

• Diazoxide has no place in the management of acute hypoglycaemia
• Sodium and water retention induced by diazoxide may be reduced by concurrent use of a diuretic
• Chlorothiazide 3- 5mg/kg twice daily has the added benefit of potentiating the glycaemic effect of diazoxide
• If diazoxide and chlorothiazide fail to suppress excessive glucose requirements then octreotide or nifedipine may be added. There is limited experience for this indication
• Octreotide may suppress growth hormone secretion, but there is little evidence that this has any long-term adverse effect on growth.