Hyperamylasaemia remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis. However, the clinical specificity of this marker for pancreatic disease can be as low as 61% depending on the patient population studied as many other intra-abdominal and salivary gland pathologies result in a raised concentration.1
Two amylase isoenzymes are present in the circulation: pancreatic type (p-amylase) and salivary type (s-amylase). P-amylase is responsible for approximately 40% of normal serum amylase activity. Initial reports suggested that p-amylase was pancreas specific; however, p-amylase has since been identified in non-pancreatic tissue such as the stomach and duodenum. Therefore, p-amylase is increased in other intra-abdominal diseases, including intestinal obstruction, perforated peptic ulcers and biliary tract disease. S-amylase is increased in tubo-ovarian pathology, alcohol abuse, diabetic ketoacidosis, septic shock, as well as salivary gland lesions. Of note, when our patient was investigated for a ruptured ovarian cyst, the serum amylase concentration was within normal limits.
Both isoenzymes are increased in renal insufficiency. While our patient's renal function was impaired renal insufficiency only results in mild elevations of amylase, usually less than five times the ULN. In addition, hyperamylasaemia can be attributable to macroamylasaemia—an IgA or IgG-bound amylase fraction that cannot be cleared by the renal glomeruli and, subsequently, has an extended half-life in the serum. However, macroamylasaemia is rarely observed in children.2
Hyperamylasaemia is also known to occur in patients with acidosis; of note our patient had a profound metabolic acidosis with a pH of 6.9 on admission to ICU. Another important cause of hyperamylasaemia to consider in adolescent females is anorexia nervosa; however, values are generally less than five times the ULN.3
The amylase concentration in this case reached 50 times the ULN and interpretation was complicated by the clinical presentation with abdominal pain. The significant hyperamylasaemia was assumed to be of pancreatic origin, and only when the serum lipase result was returned 5 days later within reference range was the hyperamylasaemia attributed to soft tissue inflammation in the salivary gland.
There are many salivary gland pathologies known to cause an increase in serum amylase; these include mumps, parotid tumours, trauma, irradiation and obstruction of the salivary duct. However, the serum amylase activity is often not as high as in our case; Howieson et al4
report a case of parotitis in which the serum amylase peaked at 1477 U/litre.
Had lipase been measured earlier in this case there would have been less concern regarding pancreatitis. Serum lipase offers a superior sensitivity and specificity for the diagnosis of acute pancreatitis; at a cut off of 600 U/litre most studies have reported specificities greater than 95% and sensitivities of 55–100%.5
Of note, lipase has a longer half-life than amylase so persists in the circulation after the onset of pancreatitis. For these reasons, the UK guidelines for the management of acute pancreatitis published in 2005 state lipase as the preferred test.5
However, assays for lipase are not routinely available in all laboratories because of analytical problems and a lack of consensus on appropriate methodology. Amylase methods specific for p-amylase are available and used by some laboratories.
In summary, our case serves to remind clinicians to consider non-pancreatic causes of hyperamylasaemia. It is important that clinicians consult with biochemistry laboratory staff to review the complete clinical presentation.
- Consider non-pancreatic causes of hyperamylasaemia when appropriate.
- Interpret biochemistry test results with knowledge of the complete clinical presentation.
- Consultation with laboratory staff to review unexpected findings or difficult diagnoses can help with result interpretation.