Amylase is a digestive enzyme predominantly secreted by the pancreas and salivary glands but also found in other tissues in very small levels. Amylase was first described in the early 1800s and is considered one of the first enzymes in history to be scientifically investigated. It was initially termed as distaste but was later renamed as amylase in the early 20th century.
The main function of amylases is to hydrolyze the glycosidic bonds in starch molecules, converting complex carbohydrates to simple sugars. There are three main classes of amylase enzymes; Alpha-, beta- and gamma-amylase, and each act on different parts of the carbohydrate molecule. Alpha-amylase can be found in humans, animals, plants, and microbes. Beta-amylase is found in microbes and plants. Gamma-amylase is found in animals and plants. This article will focus on alpha-amylase and its applications.
In 1908, a study by Wohlgemuth identified the presence of amylase in urine and this subsequently led to the use of amylase as a diagnostic laboratory test. Amylase is a commonly ordered test along with lipase especially in the setting of suspected acute pancreatitis.
Although elevated amylase or hyperamylasemia, is primarily seen in salivary and pancreatic disease, it may also be seen in different diseases including gastrointestinal diseases, malignancy, and gynecological diseases (see table below). Reduced amylase levels can be seen in preeclampsia, cystic fibrosis, and liver disease.
Elevated amylase can be seen in a variety of conditions including pancreatic disease, salivary disease, decreased metabolic clearance, intestinal disease, and macroamylasemia (discussed below). A chronic increase in amylase may also be seen in a rare condition called Benign Pancreatic Hyperenzymemia or Gullo's syndrome. Patients are typically healthy with no pancreatic disease. The etiology of the condition is unknown.Twenty-six (12.5%) of 208 patients with acute abdominal pain unrelated to the pancreas had elevated serum amylase on admission. Abnormally elevated amylase levels is seen in 35% of patients with liver disease. 16-25% of diabetic ketoacidosis cases present with elevated levels of amylase . In a group of 74 patients with surgically resectable lung cancer, 13 showed hyperamylasemia.
The main function of amylase is to catalyze the hydrolysis of starch into sugars. Several isoforms of amylase have been discovered but the most abundant that exist are pancreatic amylase (P-amylase) and salivary amylase (S-amylase)P-amylase is specifically found in the pancreas and is synthesized by acinar cells then secreted into the gastrointestinal tract. S-amylase is primarily produced in salivary glands, but can also be produced in ovaries, fallopian tubes, gastrointestinal tract, lungs, striated muscle, and malignant neoplasms. Serum amylase is tightly regulated in the body. There is a balance between the rate of production and the rate of clearance. Elevated amylase may be due to an increase in pancreatic or extrapancreatic production of a decreased rate of clearance.
Amylase has a molecular weight of about 50 to 55 kDa, an optimum physiological pH of 6.7 to 7.0, and requires calcium and chloride ions for optimal enzyme activity. The small size allows it to be easily filtered through the glomeruli. Amylase is cleared via the kidneys and reticuloendothelial system.
For many years, amylase has been primarily used for diagnosing acute pancreatitis. Amylase can be measured with a blood test or urine test. The urine test may be performed by a clean catch or 24-hour urine collection. The normal range of serum amylase differs from laboratory to laboratory. It is clinically important to differentiate pancreatic amylase from other amylase isoforms. An elevated amylase with normal lipase may be suggestive of a problem outside the pancreas.
Medications including aspirin, morphine, antiretrovirals, and estrogen-containing medication, can affect serum levels of amylase. Macroamylasemia, as referred above, is another well-recognized cause of elevated serum amylase. In this condition, the enzyme forms a complex with proteins such as immunoglobulins and polysaccharides. Due to the large size of the macromolecular complex, renal clearance is reduced, causing persistently elevated amylase levels. Macroamylasemia can occur in healthy individuals or in diseases including autoimmune disease, diabetes, and cancer such as thyroid cancer.
Urinary amylase is typically normal macroamylasemia and can help exclude the condition. This condition occurs in 1 percent of healthy individuals and in 2.5 percent of individuals with hyperamylasemia. Macroamylasemia should be considered in an asymptomatic patient with elevated serum amylase. There is no required treatment for the condition. Past studies have shown that macroamylasemia was primarily reported in patients with impaired humoral immunity, such as those with celiac disease, HIV infection, ulcerative colitis, rheumatoid arthritis, and multiple myeloma.
Currently, there is no internationally established reference range for amylase levels. The reference range can be as wide as 20-300 U/L. However, elevated amylase levels of more than three times the upper limit of normal strongly supports the diagnosis of acute pancreatitis. Less than this is often associated with other conditions. Abnormally low levels of amylase is not common but can be observed in cystic fibrosis, chronic pancreatitis, diabetes mellitus, obesity, and smoking. Clinicians should be aware of such causes to help to interpret low amylase activity in patients.
Amylase is primarily used in diagnosing pancreatic diseases. Amylase is a commonly measured enzyme due to the availability of inexpensive, easily automated methods. Although amylase is a sensitive indicator of acute pancreatitis, it is not specific as it can be elevated in several conditions unrelated to the pancreas. Pancreatitis can be defined by two out of the three following criteria: abdominal pain, serum amylase and/or lipase levels more than three times the upper limit of normal, and abdominal imaging supporting characteristic findings of pancreatitis. Therefore, its clinical significance has been questioned. In cases of elevated levels of amylase with little support for pancreatitis, alternative causes of hyperamylasaemia should be considered. Amylase is not useful in predicting the severity of an acute pancreatic episode or monitoring the condition.
Amylase inhibitors such as acarbose have been used in the treatment of type 2 diabetes and have shown to reduce Hemoglobin A1C and peak postprandial glucose. Acarbose has also been shown to improve remission of dumping syndrome in bariatric patients. The drug also has also shown to improve the risk of cardiovascular disease by slowing down the thickening of carotid arteries. Elevated amylase can be seen in a wide variety of conditions. It is important for clinicians to have a clear, stepwise approach when hyperamylasemia is found. This will help avoid unnecessary hospitalization and delayed or inappropriate treatment.
It is crucial that health care workers communicate effectively when laboratory results point towards a non-pancreatic cause. It is also important to be knowledgeable of the different conditions that may affect amylase levels. Lipase is typically preferred instead of amylase due to higher specificity. Lipase typically stays elevated for up to two weeks, while amylase concentrations remain elevated for up to five days. Therefore, amylase is not as clinically useful as lipase if there is a delay between symptom onset and the time the patient seeks medical attention. The 2013 American College of Gastroenterology mentions co-ordering lipase and amylase is neither cost-effective nor treatment advantageous. It also states that ordering amylase alone is unreliable and does not increase diagnostic efficiency compared to lipase. If there is access to lipase testing, adding amylase simply increases the cost to the patient and has little value in supporting the diagnosis of pancreatitis.
|||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]|
|||Zakowski JJ,Bruns DE, Biochemistry of human alpha amylase isoenzymes. Critical reviews in clinical laboratory sciences. 1985; [PubMed PMID: 2578342]|
|||Azzopardi E,Lloyd C,Teixeira SR,Conlan RS,Whitaker IS, Clinical applications of amylase: Novel perspectives. Surgery. 2016 Jul; [PubMed PMID: 27117578]|
|||Corlette MB,Dratch M,Sorger K, Amylase elevation attributable to an ovarian neoplasm. Gastroenterology. 1978 May; [PubMed PMID: 640346]|
|||Hayakawa T,Kameya A,Mizuno R,Noda A,Kondo T,Hirabayashi N, Hyperamylasemia with papillary serous cystadenocarcinoma of the ovary. Cancer. 1984 Oct 15; [PubMed PMID: 6206939]|
|||Katayama S,Ikeuchi M,Kanazawa Y,Akanuma Y,Kosaka K,Takeuchi T,Nakayama T, Amylase-producing lung cancer: case report and review of the literature. Cancer. 1981 Dec 1; [PubMed PMID: 6170423]|
|||Srivastava R,Fraser C,Gentleman D,Jamieson LA,Murphy MJ, Hyperamylasaemia: not the usual suspects. BMJ (Clinical research ed.). 2005 Oct 15; [PubMed PMID: 16223823]|
|||Terui K,Hishiki T,Saito T,Mitsunaga T,Nakata M,Yoshida H, Urinary amylase/urinary creatinine ratio (uAm/uCr)--a less-invasive parameter for management of hyperamylasemia. BMC pediatrics. 2013 Dec 13; [PubMed PMID: 24330759]|
|||Nitsche CJ,Jamieson N,Lerch MM,Mayerle JV, Drug induced pancreatitis. Best practice [PubMed PMID: 20227028]|
|||Andersen V,Sonne J,Andersen M, Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999. European journal of clinical pharmacology. 2001 Sep; [PubMed PMID: 11699619]|
|||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]|
|||Rosell-Camps A,Martínez-Cepas P,Riera-Llodrá JM,Ventura-Espejo L,Riutord-Arrom N, Benign Pancreatic Hyperenzymemia, Also Known as Gullo's Syndrome. Laboratory medicine. 2019 Dec 20; [PubMed PMID: 31860089]|
|||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]|
|||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]|
|||Rizvi AA, Serum amylase and lipase in diabetic ketoacidosis. Diabetes care. 2003 Nov; [PubMed PMID: 14578269]|
|||Lenler-Petersen P,Grove A,Brock A,Jelnes R, alpha-Amylase in resectable lung cancer. The European respiratory journal. 1994 May; [PubMed PMID: 8050552]|
|||Lindberg T,Skude G, Amylase in human milk. Pediatrics. 1982 Aug; [PubMed PMID: 6179037]|
|||Logie JJ,Cox M,Sharkey J,Williams A, A multidisciplinary approach to an unusual cause of hyperamylasaemia. BMJ case reports. 2015 Jul 6; [PubMed PMID: 26150631]|
|||Peyrot des Gachons C,Breslin PA, Salivary Amylase: Digestion and Metabolic Syndrome. Current diabetes reports. 2016 Oct; [PubMed PMID: 27640169]|
|||Otsuki M, [Usefulness of amylase isoenzyme determination for the diagnosis of pancreatic diseases]. Nihon rinsho. Japanese journal of clinical medicine. 1995 May; [PubMed PMID: 7541479]|
|||Klonoff DC, Macroamylasemia and other immunoglobulin-complexed enzyme disorders. The Western journal of medicine. 1980 Nov; [PubMed PMID: 6162278]|
|||Wiederkehr JC,Wiederkehr BA,Wiederkehr HA,Carvalho CA, Nonspecific hyperamylasemia: a case report. JOP : Journal of the pancreas. 2013 Jan 10; [PubMed PMID: 23306339]|
|||Cutolo M,Sulli A,Barone A,Picciotto A,Mangraviti S,Seriolo B,Accardo S, Macroamylasemia: a possible cause of unexplained hyperamylasemia in rheumatoid arthritis. British journal of rheumatology. 1995 Mar; [PubMed PMID: 7537158]|
|||Ishizuka T,Yasuda K,Kajita K,Sakata S,Kimura M,Ito Y,Miura K, Macroamylasemia associated with thyroid cancer, elevated serum thyroxine-binding globulin (TBG), chronic pancreatitis and gastrointestinal polyposis. Gastroenterologia Japonica. 1986 Aug; [PubMed PMID: 2429888]|
|||Cho SY,Lee A,Lee HJ,Suh JT, Overlapping presence of macroamylasemia and hyperamylasemia in acute pancreatitis. The Korean journal of laboratory medicine. 2011 Apr; [PubMed PMID: 21474984]|
|||Rompianesi G,Hann A,Komolafe O,Pereira SP,Davidson BR,Gurusamy KS, Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitis. The Cochrane database of systematic reviews. 2017 Apr 21; [PubMed PMID: 28431198]|
|||Oh HC,Kwon CI,El Hajj II,Easler JJ,Watkins J,Fogel EL,McHenry L,Sherman S,Zimmerman MK,Lehman GA, Low Serum Pancreatic Amylase and Lipase Values Are Simple and Useful Predictors to Diagnose Chronic Pancreatitis. Gut and liver. 2017 Nov 15; [PubMed PMID: 29081212]|
|||Muniraj T,Gajendran M,Thiruvengadam S,Raghuram K,Rao S,Devaraj P, Acute pancreatitis. Disease-a-month : DM. 2012 Mar; [PubMed PMID: 22370054]|
|||Basnayake C,Ratnam D, Blood tests for acute pancreatitis. Australian prescriber. 2015 Aug; [PubMed PMID: 26648641]|
|||McInnes N,Smith A,Otto R,Vandermey J,Punthakee Z,Sherifali D,Balasubramanian K,Hall S,Gerstein HC, Piloting a Remission Strategy in Type 2 Diabetes: Results of a Randomized Controlled Trial. The Journal of clinical endocrinology and metabolism. 2017 May 1; [PubMed PMID: 28324049]|
|||Cadegiani FA,Silva OS, Acarbose promotes remission of both early and late dumping syndromes in post-bariatric patients. Diabetes, metabolic syndrome and obesity : targets and therapy. 2016; [PubMed PMID: 27994477]|
|||Yamagishi S,Matsui T,Ueda S,Fukami K,Okuda S, Clinical utility of acarbose, an alpha-glucosidase inhibitor in cardiometabolic disorders. Current drug metabolism. 2009 Feb; [PubMed PMID: 19275550]|
|||Barbieri JS,Riggio JM,Jaffe R, Amylase testing for abdominal pain and suspected acute pancreatitis. Journal of hospital medicine. 2016 May; [PubMed PMID: 27160507]|
|||Beauregard JM,Lyon JA,Slovis C, Using the literature to evaluate diagnostic tests: amylase or lipase for diagnosing acute pancreatitis? Journal of the Medical Library Association : JMLA. 2007 Apr; [PubMed PMID: 17443244]|