ELEVATED SERUM AMYLASE
M. Angelo Trujillo, MD
A. Amylase is an enzyme with a 55,000-dalton molecular
weight that hydrolyzes starch. The pancreas and salivary
glands contain very high concentrations of amylase.
Amylase also is produced by a number of other organs
in lower concentrations. Approximately 35%–45% of
normal serum amylase is of pancreatic origin. Amylase
has a serum half-life of 1–2 hours. Approximately
20% of circulating amylase is excreted in the urine; the
remainder is catabolized at an unknown site. Increased
serum amylase is most commonly caused by pancreati-
tis, but hyperamylasemia may be associated with several
other nonpancreatic or nonabdominal disorders with
similar clinical presentations.
B. In acute pancreatitis serum amylase increases within
24–48 hours of the acute onset of pancreatitis. Levels
return to normal within 3–5 days in most cases. A nor-
mal serum amylase level occasionally is seen in acute
pancreatitis. This may represent early pancreatitis,
after a transient rise and fall of amylase, extensive pan-
creatic necrosis with inability to produce amylase, or
cases of acute exacerbation of chronic pancreatitis in
which the gland cannot produce amylase. Serum amy-
lase also may be normal when pancreatitis is associated
with hypertriglyceridemia. In this case, a urinary
amylase measurement usually shows a marked eleva-
tion. Cholelithiasis, ethanol, and idiopathic causes are
responsible for about 90% of all cases of acute pancre-
atitis. Commonly used drugs known to cause pancreati-
tis include ethanol, hydrochlorothiazide, furosemide,
sulfonamides, tetracyclines, estrogens, valproate, and
azathioprine. A serum amylase level ⬎3 times the up-
per limit of normal is consistent with pancreatitis.
Other abdominal processes usually do not cause amy-
lase levels ⬎2–2.5 times the upper limit of normal, with
the exception of salivary gland disease and gut perfora-
tion or infarction.
C. In acute pancreatitis with persistent elevated serum
amylase levels, complications of acute pancreatitis as
listed should be considered. Abdominal CT is useful in
identifying pseudocysts, abscesses, ascites, and some
tumors: Consider MRI of the pancreas with magnetic
resonance cholangiopancreatography (MRCP) or endo-
scopic ultrasound (EUS), or consider endoscopic retro-
grade cholangiopancreatography (ERCP) in pancreatitis
of biliary origin or idiopathic pancreatitis. This would be
of low yield if the CT, MRI, MRCP, and EUS results are
negative.
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D. In a patient with epigastric pain and elevated serum
amylase, rule out causes other than acute pancreatitis.
In cases of perforated viscus (esophagus, stomach, small
intestine, colon), peritoneal absorption of GI contents
results in elevated serum amylase. The patient usually
has a more abrupt onset of pain and more peritoneal
irritation. Several other nonpancreatic conditions listed
also present with more pronounced signs of peritonitis,
and most need surgical intervention.
E. The elevation of serum amylase in renal insufficiency
usually is modest, seldom ⬎2 times the upper limit of
normal. Macroamylasemia is a condition in which the
major portion of serum amylase is bound to immuno-
globin. A (IgA). These macromolecular aggregates can-
not undergo glomerular filtration, so the urine amylase
level is low or normal. The amylase/creatinine clear-
ance ratio (ACR) is calculated as follows:
A (urine) ⫻ CR (serum)
ACR = ⫻ 100
A (serum) ⫻ CR (urine)
where A ⫽ amylase concentration and CR ⫽ creati-
nine concentration. In macroamylasemia, the ACR is
abnormally low (usually ⬍0.2%).
F. After the common causes have been considered, more
obscure causes should be sought. Isoamylase or lipase
measurements may be helpful. Elevated serum amylase
secondary to lung disease or certain tumors is com-
monly of the salivary or s-isoenzyme. Alcoholic patients
may have an elevated serum amylase of salivary origin.
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