Hyperamylasemia

Article Author:
Robert Lam
Article Editor:
Thiruvengadam Muniraj
Updated:
6/28/2020 10:42:17 AM
PubMed Link:
Hyperamylasemia

Introduction

Hyperamylasemia refers to an elevated level of serum amylase beyond the upper limit of normal (normal range is typically 30 U/L to 110U/L). Amylase is an enzyme produced in two isoforms, P-type amylase (60%) and S-type amylase (40%). Amylase cleaves carbohydrate sugars into smaller chains and monosaccharides. P-type amylase is secreted from the pancreas, while S-type amylase is secreted from the salivary glands. The clearance of amylase occurs through the kidney (25%) and the reticuloendothelial system (75%).[1][2]

Etiology

Hyperamylasemia can be from pancreatic source, salivary gland origin, or other etiologies. Pancreatic causes of hyperamylasemia include: 

  • Acute pancreatitis usually presenting with severe epigastric abdominal pain and elevations of serum amylase beyond three times the upper limit of normal
  • Trauma including blunt trauma, surgery, or recent endoscopic retrograde cholangiopancreatography (ERCP) of the pancreatic duct leading to release of amylase enzyme from within pancreatic cells
  • Chronic pancreatitis
  • Pancreatic pseudocysts

 Salivary gland causes include:

  • Trauma to the salivary gland
  • Radiation to the neck area involving the parotid gland
  • Salivary gland obstruction with calculi

Decreased metabolic clearance of amylase can also lead to hyperamylasemia and can be due to:

  • Renal failure
  • Liver failure (i.e., hepatitis or cirrhosis)

 Other known etiologies of hyperamylasemia include: 

  • Macroamylasemia
  • Intestinal disease (e.g., inflammatory disease of the small intestine, mesenteric ischemia, intestinal obstruction, peritonitis)
  • Female reproductive tract disease (e.g., ruptured ectopic pregnancy, fallopian or ovarian cysts, salpingitis)
  • Malignancy (e.g., lung, ovary, pancreas, pheochromocytoma, thymoma, multiple myeloma, breast)
  • Acidosis (ketoacidosis and nonketotic acidosis)[3]

Epidemiology

Amylase levels are routinely evaluated in patients suspected of acute pancreatitis. However, while it is sensitive, it is not specific.[4] In a study involving 1000 emergency department patients presenting with abdominal pain, 39% of individuals received a test for amylase, but only 3.9% of individuals were diagnosed with pancreatitis.[5] Furthermore, in patients with nonpancreatic abdominal pain, 11% to 13% of patients have elevated pancreatic enzymes.[6] Hyperamylasemia is common following cardiac surgery and occurs in 30% to 60% of patients.[7]

Appropriate reference ranges should be applied to assess serum amylase levels as they differ based on age and different ethno-racial groups. A study found that 32% of Asian Americans and 50% of Native Americans had higher total amylase levels above the upper limit of normal compared to Caucasians.[8] Another study found that the total serum amylase was higher in the elderly for both men and women potentially as a result of age-related decrease in renal clearance.[9]

Pathophysiology

Hyperamylasemia is due to impaired metabolic clearance or pathology involving the organs containing amylase enzyme. In acute pancreatitis, inflammation of pancreatic cells leads to the secretion of amylase into the bloodstream. Pathologies that involve trauma of the organs, such as blunt trauma to the pancreas or parotid gland or even endoscopic retrograde cholangiopancreatography (ERCP) to the pancreatic duct, can lead to the release of stored amylase. Given amylase is cleared by the kidney and the reticuloendothelial system, renal failure and liver disease (i.e., hepatitis or cirrhosis) are associated with hyperamylasemia. Chronic alcohol abuse can also lead to hyperamylasemia and is thought to be related to liver damage.[10]

History and Physical

As a result of the various etiologies responsible for hyperamylasemia, a detailed history will aide in the identification of the underlying disease.

Acute pancreatitis should be suspected in patients with serum amylase levels beyond three times the upper limit of normal who present with acute epigastric pain and abdominal tenderness on physical examination.

Parotid duct obstruction should be suspected if patients present with hyperamylasemia in the setting of parotid gland tenderness and history of sialolithiasis.

Inquire if the patient has had any recent history of endoscopic retrograde cholangiopancreatography (ERCP), trauma, or surgery. In a pediatric patient, assess if the patient is up-to-date with vaccination to rule mumps infection.

Evaluate if the patient has a prior history of alcohol abuse, inflammatory bowel disease, renal failure, liver disease, or family history of pancreatitis.

Evaluation

Serum amylase is primarily used to support the diagnosis of acute pancreatitis despite its low specificity. If the patient has severe epigastric pain that can be reproduced on palpation during a physical examination and has a serum amylase elevated to three times the upper limit of normal or higher, a diagnosis of acute pancreatitis can be made without further imaging. Serum lipase can also be collected, though the co-ordering of both tests has not been shown to increase diagnostic sensitivity and specificity.[4]

If abdominal pain is associated with an elevated serum amylase but less than three times the upper limit of normal, additional imaging with computed tomography (CT scan) with contrast can be made. Additional laboratory workup such as complete blood count, basic metabolic panel, alanine aminotransferase (ALT), calcium, albumin, aspartate aminotransferase (AST), and direct and total bilirubin can also be obtained to guide the diagnosis. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatogram (MRCP) can also be used to elucidate pancreatic pathologies and may reveal pancreatic pseudocysts or ascites.[11]

Amylase levels can also be obtained after an endoscopic retrograde cholangiopancreatogram (ERCP) due to its value in predicting postprocedure pancreatitis.[12]

In patients with isolated amylase elevation without the presence of any other symptoms, the diagnosis of macroamylasemia should be considered. Macroamylasemia occurs in settings of inflammatory states, including celiac disease, rheumatoid arthritis, and monoclonal gammopathy. In the inflammatory state, amylase is bound to macromolecules such as immunoglobins and polysaccharides to form large complexes. These complexes are too large to be excreted by the kidney and results in isolated hyperamylasemia. Macroamylasemia is diagnosed using the amylase-to-creatinine clearance ratio (ACCR). ACCR is reduced to a ratio of less than one in macroamylasemia due to poor filtration of the large macroamylase complexes. The formula is as follows:

ACCR = [Amylase (urine) x creatinine (serum) x 100]/[amylase (serum) x Creatinine (urine)][13]

For patients with isolated hyperamylasemia negative for macroamylasemia or abdominal pain with no other specific signs or symptoms to suggest alternative diagnoses, no further evaluation is needed.

Treatment / Management

Treatment of hyperamylasemia will be directed at the suspected underlying etiology. Asymptomatic isolated hyperamylasemia without suspicion of any underlying etiology is benign and does not warrant treatment.

In acute pancreatitis, treatment is directed toward fluid resuscitation with an isotonic crystalloid solution (i.e., normal saline or lactated Ringer’s solution), pain control, and nutrition. Fluid resuscitation is typically provided at a rate of 5 cc/kg/hr to 10 cc/kg/hr for all patients. In patients with severe volume loss, rapid repletion should be given with up to 20 cc/kg of fluid over 30 minutes, followed by 3 cc/kg/hr for 8 to 12 hrs. Reassess fluid requirements every 6 hours over the next 24 to 48 hours based on clinical assessment of volume status, creatinine, and blood urea nitrogen (BUN) values. The target heart rate should be less than 120 beats/minute with mean arterial pressure between 65 mmHg to 85 mmHg, and urine output of at least 0.5 cc/kg/hr to 1 cc/kg/hr. Pain control should be managed with analgesics and in severe cases of pain. For most mild cases of acute pancreatitis, patients can be managed with intravenous (IV) fluids and resume a low-fat solid diet within 24 hours as tolerated if pain and nausea/vomiting symptoms are improving.[14]

Differential Diagnosis

Differential diagnosis can be sorted by pancreatic, salivary gland, and miscellaneous etiologies:

 Pancreatic

  • Acute/chronic pancreatitis
  • Complications of acute pancreatitis including abscess, pseudocyst, ascites
  • Trauma (ERCP, blunt trauma, recent surgery)
  • Malignancy (pancreatic carcinoma)

 Salivary gland

  • Duct obstruction/calculi
  • Chronic alcohol abuse
  • Trauma (blunt trauma, recent surgery)
  • Mumps
  • Sjogren syndrome
  • Anorexia/bulimia

Miscellaneous:

  • Macroamylasemia
  • Malignancy (ovary, renal cell, breast, thymoma, multiple myeloma, pheochromocytoma, colon)
  • Inflammatory bowel disease
  • Renal failure
  • Liver disease (hepatitis, cirrhosis, hepatocellular carcinoma)
  • Ketotic and non-ketotic acidosis

Prognosis

Prolonged hyperamylasemia for over a week after an initial episode of acute pancreatitis may be associated with future recurrence.[15] However, amylase level does not play a role in determining the severity or the etiology of acute pancreatitis.[16] There is no benefit of trending amylase levels once the diagnosis of acute pancreatitis has been made.[6]

Complications

Prolonged hyperamylasemia has been shown to be associated with complications of acute pancreatitis, specifically the presence of pancreatic pseudocysts, necrosis, or abscess.[17] Prolonged hyperamylasemia has also been shown to be independently associated with alcohol use.[15] Serum lipase to amylase ratio may be used to determine the etiology of acute pancreatitis, with a higher ratio positively correlating with the specificity of alcohol as the etiology.[18] However, a prospective follow-up study was unable to confirm the finding.[19]

Deterrence and Patient Education

Patients should be educated about the relevance of testing for serum amylase to rule out certain diagnoses. In its most common use, healthcare providers should explain that serum amylase will be an important data point to guide the diagnosis of acute pancreatitis. They should be educated that there is no clinical value to trending amylase levels as it does not determine the severity of acute pancreatitis. Patients can be educated that imaging studies may also be conducted in conjunction with lab work to rule out high suspicion of acute pancreatitis. Hyperamylasemia, without suspicion of any other underlying pathology, does not need further workup or intervention.

Enhancing Healthcare Team Outcomes

Management of hyperamylasemia involves an interprofessional team potentially consisting of a gastroenterologist, emergency physician, internist, or family medicine physician. Amylase levels will most commonly be assessed in the acute care setting when ruling out the diagnosis of acute pancreatitis. Gastroenterologists may evaluate serum amylase levels post-ERCP to assess for post-procedural pancreatitis.[20] Prolonged hyperamylasemia beyond one week after an initial episode of acute pancreatitis may be associated with complications of pseudocysts or necrosis and may involve surgical consultation.[21] Overall, serum amylase is a data point requiring correlation to clinical presentation. [Level 3]


References

[1] Argiris A,Mathur-Wagh U,Wilets I,Mildvan D, Abnormalities of serum amylase and lipase in HIV-positive patients. The American journal of gastroenterology. 1999 May;     [PubMed PMID: 10235202]
[2] Pieper-Bigelow C,Strocchi A,Levitt MD, Where does serum amylase come from and where does it go? Gastroenterology clinics of North America. 1990 Dec;     [PubMed PMID: 1702756]
[3] Muniraj T,Dang S,Pitchumoni CS, PANCREATITIS OR NOT?--Elevated lipase and amylase in ICU patients. Journal of critical care. 2015 Dec     [PubMed PMID: 26411523]
[4] Yadav D,Agarwal N,Pitchumoni CS, A critical evaluation of laboratory tests in acute pancreatitis. The American journal of gastroenterology. 2002 Jun;     [PubMed PMID: 12094843]
[5] Powers RD,Guertler AT, Abdominal pain in the ED: stability and change over 20 years. The American journal of emergency medicine. 1995 May;     [PubMed PMID: 7755822]
[6] Chase CW,Barker DE,Russell WL,Burns RP, Serum amylase and lipase in the evaluation of acute abdominal pain. The American surgeon. 1996 Dec;     [PubMed PMID: 8955242]
[7] Wan S,Arifi AA,Chan CS,Ng CS,Wan IY,Lee TW,Yim AP, Is hyperamylasemia after cardiac surgery due to cardiopulmonary bypass? Asian cardiovascular     [PubMed PMID: 12079932]
[8] Tsianos EB,Jalali MT,Gowenlock AH,Braganza JM, Ethnic 'hyperamylasaemia': clarification by isoamylase analysis. Clinica chimica acta; international journal of clinical chemistry. 1982 Sep 1;     [PubMed PMID: 6181916]
[9] Ueda M,Araki T,Shiota T,Taketa K, Age and sex-dependent alterations of serum amylase and isoamylase levels in normal human adults. Journal of gastroenterology. 1994 Apr;     [PubMed PMID: 7516788]
[10] Pezzilli R,Andreone P,Morselli-Labate AM,Sama C,Billi P,Cursaro C,Barakat B,Gramenzi A,Fiocchi M,Miglio F,Bernardi M, Serum pancreatic enzyme concentrations in chronic viral liver diseases. Digestive diseases and sciences. 1999 Feb;     [PubMed PMID: 10063922]
[11] Mortelé KJ,Wiesner W,Zou KH,Ros PR,Silverman SG, Asymptomatic nonspecific serum hyperamylasemia and hyperlipasemia: spectrum of MRCP findings and clinical implications. Abdominal imaging. 2004 Jan-Feb;     [PubMed PMID: 15160763]
[12] Christoforidis E,Goulimaris I,Kanellos I,Tsalis K,Demetriades C,Betsis D, Post-ERCP pancreatitis and hyperamylasemia: patient-related and operative risk factors. Endoscopy. 2002 Apr;     [PubMed PMID: 11932783]
[13] Dreiling DA,Leichtling JJ,Janowitz HD, The amylase-creatinine clearance ratio. Diagnostic parameter or physiologic phenomenon? The American journal of gastroenterology. 1974 Apr;     [PubMed PMID: 4831310]
[14] Chatila AT,Bilal M,Guturu P, Evaluation and management of acute pancreatitis. World journal of clinical cases. 2019 May 6;     [PubMed PMID: 31123673]
[15] Kim YS,Chang JH,Kim TH,Kim CW,Kim JK,Han SW, Prolonged hyperamylasemia in patients with acute pancreatitis is associated with recurrence of acute pancreatitis. Medicine. 2020 Jan;     [PubMed PMID: 32011507]
[16] Papachristou GI,Whitcomb DC, Predictors of severity and necrosis in acute pancreatitis. Gastroenterology clinics of North America. 2004 Dec;     [PubMed PMID: 15528023]
[17] Schmidt J,Lewandrowski K,Fernandez-del Castillo C,Mandavilli U,Compton CC,Warshaw AL,Rattner DW, Histopathologic correlates of serum amylase activity in acute experimental pancreatitis. Digestive diseases and sciences. 1992 Sep;     [PubMed PMID: 1380425]
[18] Tenner SM,Steinberg W, The admission serum lipase:amylase ratio differentiates alcoholic from nonalcoholic acute pancreatitis. The American journal of gastroenterology. 1992 Dec;     [PubMed PMID: 1280405]
[19] Pezzilli R,Billi P,Barakat B,Miglio F, Lipase-amylase ratio does not determine the etiology of acute pancreatitis. Another myth bites the dust. Journal of clinical gastroenterology. 1998 Jan;     [PubMed PMID: 9492861]
[20] Ito K,Fujita N,Noda Y,Kobayashi G,Horaguchi J,Takasawa O,Obana T, Relationship between post-ERCP pancreatitis and the change of serum amylase level after the procedure. World journal of gastroenterology. 2007 Jul 28;     [PubMed PMID: 17657841]
[21] Ocampo C,Oría A,Zandalazini H,Silva W,Kohan G,Chiapetta L,Alvarez J, Treatment of acute pancreatic pseudocysts after severe acute pancreatitis. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2007 Mar;     [PubMed PMID: 17458611]