Hypoglycaemia can be defined as a plasma glucose of <2.5 mmol/L with symptoms of neuroglycopaenia. The mechanisms include excessive or inappropriate insulin, impaired counter-regulatory hormonal response (e.g. GH or cortisol) and impaired hepatic glucose output because of liver disease. The causes of spontaneous hypoglycaemia are broadly categorised into two groups according to whether the symptoms occur in the fasting or postprandial state.
The symptoms of fasting hypoglycaemia occur several hours bafter food (e.g. on waking or at night) or can be precipitated by exercise (Figure 34.1). Causes include:
• Drugs (insulin, sulphonylureas, quinine, salicylates, alcohol)
• Organ failure (liver/renal failure)
• Hormone deficiency (Addison’s disease, hypopituitarism)
• Insulinoma (Figure 34.2)
• Non-islet cell tumours (fibrosarcoma, hepatocellular carcinoma, mesothelioma)
• Autoimmune (insulin receptor-stimulating antibodies)
• Infection (septicaemia, malaria)
• Inborn errors of metabolism (glycogen storage disease, hereditary fructose intolerance, maple syrup disease)
• Beta cell hyperplasia.
Symptoms usually occur 2–5 hours after food. Causes include:
• Incipient diabetes mellitus.
The history should look to elucidate adrenergic (pallor, sweating, tachycardia, tremor) and neuroglycopaenic (impaired concentration, irritability, change in behaviour, confusion, seizures or coma) symptoms in addition to clarifying whether they occur in the fasting or postprandial state. A history of relevant drug exposure, known diabetes, renal, liver or endocrine disease should be sought. Fingerprick capillary glucose readings (‘BMs’) are unreliable for low glucose concentrations, hence a laboratory plasma glucose should always be measured to confirm true hypoglycaemia (<2.5 mmol/L). Liver and renal function should be checked, in addition to a septic screen and ethanol levels if relevant. A Synacthen test should be considered to exclude adrenal insufficiency.
Further investigation of fasting hypoglycaemia
Rarer causes of fasting hypoglycaemia should be considered if the above tests are normal. Fasting insulin, C-peptide, ketones and glucose should be measured during a confirmed episode of hypoglycaemia (Table 34.1). This may need to be undertaken as part of a prolonged (up to 72 hours) supervised fast. In the presence of hypoglycaemia, inappropriately elevated insulin suggests insulinoma or exogenous insulin or sulphonylurea therapy. The C-peptide will be suppressed in patients on exogenous insulin but inappropriately elevated in insulinoma or sulphonylurea therapy. Ketones will also be suppressed in the presence of insulin.
Further investigation of postprandial hypoglycaemia
A prolonged 75 g OGTT with frequent measurement of glucose for up to 6 hours can confirm postprandial hypoglycaemia.
The acute treatment of hypoglycaemia is detailed in Chapter 54. Treatment is directed at the underlying cause. Insulinomas should undergo surgical resection if possible, after appropriate localisation. Islet tumours can be difficult to localise as they are often small. Several tests may be needed including MRI/CT (first line), endoscopic ultrasound, octreotide scanning and/or selective venous sampling. Where surgery is not curative or not feasible, symptoms can be controlled by diazoxide or octreotide. Postprandial hypoglycaemia can be treated with a low carbohydrate diet and/or frequent small meals in the first instance.