Order Code
2216
Preferred Specimen
Collect 2 mL of serum using an SST tube. Allow the sample to clot upright for a minimum of 30 minutes, then centrifuge within 2 hours after collection. Store refrigerated.
ContainerType
Serum separator tube
Alternate Specimen Requirements
Obtain 2 mL of serum in a plain red top tube. Let the sample clot in an upright position for at least 60 minutes before centrifugation. Transfer the serum to a plastic transport tube within 2 hours of collection, clearly labeling it as serum from a plain red top tube. Refrigerate promptly.
Minimum Volume
Adult: 1 mL serum
Pediatric: 0.2 mL serum (does not allow for repeat or
additional testing).
Transport Temperature
Refrigerated
Expected Turnaround Time
1 day
Specimen Stability
1 week room temperature; 1 week refrigerated; 1 year frozen
Methodology
Roche COBAS enzymatic colorimetric assay, acc. To ifcc/szasz
Rejection Criteria
- Moderate or greater hemolysis
Overview
Gamma-glutamyl transpeptidase (GGT) is an enzyme localized in the cell membranes of hepatocytes and biliary epithelial cells, but it is also present in organs such as the kidney, pancreas, spleen, heart, brain, and seminal vesicles. GGT’s primary role involves catalyzing the transfer of the gamma-glutamyl moiety from glutathione and related compounds to peptide acceptors, facilitating amino acid transport across cell membranes (Ghadban 2013). Elevated GGT levels are commonly observed in conditions affecting the liver, biliary system, and pancreas.
From a clinical perspective, GGT is a highly sensitive yet nonspecific marker for liver disease and can be elevated in a variety of pathological states. Serum GGT levels often rise in conjunction with alkaline phosphatase in liver disorders (Pratt 1999). A key clinical application of GGT testing is to help differentiate whether an elevated alkaline phosphatase originates from liver or bone disease. Additionally, GGT measurement is valuable in screening for alcohol misuse and in monitoring patient response to treatment.
Clinical Significance
Aid in diagnosis and monitoring of hepatobiliary disease
- Obstructive jaundice/Biliary obstruction
- Alkaline phosphatase will be elevated out of proportion to serum aminotransferases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); GGT is used to confirm hepatic origin causing alkaline phosphatase elevation. GGT is more sensitive than alkaline phosphatase, the transaminases, and leucine aminopeptidase in detecting obstructive jaundice, cholangitis, and cholecystitis.
- GGT levels can be 5 to 50 times upper limit of normal.
- Choledocholithiasis
- GGT is elevated along with serum bilirubin, alkaline phosphatase; defined as the cholestatic pattern after the initial elevation of AST or ALT.
- GGT and bilirubin when elevated are most sensitive for choledocholithiasis and can be used as an independent predictor of a common bile duct stone (Yang 2008).
- If lab value improves, patient has spontaneously passed the gallstone.
- Cholangitis
- Intrahepatic cholestasis
- Pregnancy/Postpartum
- Typically, GGT values remain normal during pregnancy thus elevations are clinically significant.
- Drug-induced
- If GGT is elevated disproportionately compared to alkaline phosphatase, suspect this diagnosis
- Pregnancy/Postpartum
- Infectious hepatitis
- GGT will only be elevated about 5 times the upper limit of normal.
- Hepatoma
- Very high GGT levels can be found in ascitic fluid.
- Liver Cirrhosis
- Elevated levels of GGT in conjunction with other laboratory tests including serum aminotransferases, alkaline phosphatase, bilirubin, albumin, and prothrombin time diagnose cirrhosis.
- Levels are highest when cirrhosis is due to alcohol use.
- Increased GGT levels also found in ascitic fluid of those with alcoholic cirrhosis.
- Cystic Fibrosis: CF-related liver disease (CFLD)
- Early elevations of GGT at the upper limit of normal correlate with development of advanced liver disease (Boedewes 2015; Woodruff 2017).
- GGT included in criteria for diagnosis of CFLD along with other parameters: Imaging, liver biopsy, and physical exam findings (Koh 2017).
- GGT criteria: >1.5 to 2 times the upper limit of normal for >6 months
- Cancer (primary pancreas and metastasis to the liver)
- Useful tumor marker in correlation with CEA, alkaline phosphatase especially in liver metastasis from primaries such as colon and breast.
- Increased GGT levels correlate with tumor progression and decreasing levels correlate with response to treatment (Sahm 1983).
Aid in screening and monitoring occult alcohol use
- Isolated GGT elevations with normal alkaline phosphatase can indicate excessive alcohol use.
- If GGT at least 2x the upper limit of normal along with AST:ALT ratio that is 2:1 respectively strongly suggests alcohol abuse (Pratt 2000).
- Serial determinations of serum GGT, AST, and ALT levels can distinguish recovering alcoholics who resume drinking from those who remain abstinent (Irwin 1988 and Frimpong 1989).
Additional Information
Other miscellaneous causes of increased GGT:
- Renal failure: 10% of patients have unexplained elevation in GGT; usually within normal limits
- Systemic Lupus Erythematous
- Epstein-Barr virus
- Pancreatitis: Especially if caused by obstruction such as gallstone in the common bile duct
- Glycogen Storage Disease
- Increased body mass
- Diabetes
In recent years, elevated GGT has been associated with increased risk of coronary heart disease and atherosclerosis (Ndrepepa 2018), diabetes, metabolic syndrome, and all-cause mortality (Koenig 2015).
Limitations
- GGT activity can be induced by drugs. Medications that may increase GGT levels include: Carbamazepine, cimetidine, furosemide, heparin, isotretinoin, methotrexate, oral contraceptives, phenobarbital, phenytoin, and valproic acid. Values can be up 2 to 5x reference limits, particularly with phenytoin (Dufour 2000).
- Smoking may cause elevated levels
References
Barouki R, Chobert MN, Finidori J, Aggerbeck M, Nalpas B, Hanoune J. Ethanol effects in a rat hepatoma cell line: induction of gamma-glutamyltransferase. Hepatology. 1983;3(3):323-329.6132864
Bodewes FA, van der Doef HP, Houwen RH, Verkade HJ. Increase of Serum γ-Glutamyltransferase Associated With Development of Cirrhotic Cystic Fibrosis Liver Disease. J Pediatr Gastroenterol Nutr. 2015;61(1):113-118.25658056
Cabrera-Abreu JC, Green A. Gamma-glutamyltransferase: value of its measurement in paediatrics. Ann Clin Biochem. 2002;39(Pt 1):22-25.11853185
Daeppen JB, Smith TL, and Schuckit MA, Influence of age and body mass index on gamma-glutamyltransferase activity: A 15-year follow-up evaluation in a community sample. Alcohol Clin Exp Res. 1998;22(4):941-944.9660326
Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin Chem. 2000 Dec;46(12):2027-2049.11106349
Fine A, McIntosh WB. Elevation of serum gamma-glutamyl transpeptidase in end-stage chronic renal failure. Scott Med J. 1975 May;20(3):113-115.242073
Frimpong NA, Lapp JA. Effects of moderate alcohol intake in fixed or variable amounts on concentration of serum lipids and liver enzymes in healthy young men. Am J Clin Nutr. 1989;50(5):987-991.2573268
Ghadban R. Gamma-Glutamyltransferase. Medscape website. http://emedicine.medscape.com/. Updated December 11, 2013. Accessed May 6, 2019.
Goldberg DM. Structural, functional, and clinical aspects of gamma-glutamyltransferase. CRC Crit Rev Clin Lab Sci. 1980;12(1):1-58.6104563
Hadzagic-Catibusic F, Hasanbegovic E, Melunovic M, Zubcevic S, Uzicanin S. Effects of Carbamazepine and Valproate on Serum Aspartate Aminotransferase, Alanine Aminotransferase and Gamma – Glutamyltransferase in Children. Med Arch. 2017;71(4):239-242.28974841
Irwin M, Baird S, Smith TL, Schuckit M. Use of laboratory tests to monitor heavy drinking by alcoholic men discharged from a treatment program. Am J Psychiatry. 1988;145(5):595-5992895984
Koh C, Sakiani S, Surana P, et al. Adult-onset cystic fibrosis liver disease: Diagnosis and characterization of an underappreciated entity. Hepatology. 2017;66(2):591-601.28422310
Koenig G, Seneff S. Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk. Dis Markers. 2015;2015:818570.26543300
Lippi G, Salvagno GL, Montagnana M, Brocco G, Guidi GC. Influence of hemolysis on routine clinical chemistry testing. Clin Chem Lab Med. 2006;44(3):311-316.16519604
Ndrepepa G, Colleran R, Kastrati A. Gamma-glutamyl transferase and the risk of atherosclerosis and coronary heart disease. Clin Chim Acta. 2018;476:130-138.29175647
Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. 2000;342(17):1266-1271.10781624
Pratt, D, Kaplan, M. Evaluation of the liver: Laboratory Tests. Schiff’s Disease of the Liver. 8th ed. Lippincott Williams & Wilkens, Philadelphia. 1999. pp 205.
Robinson D, Whitehead TP. Effect of body mass and other factors on serum liver enzyme levels in men attending for well population screening. Ann Clin Biochem. 1989;26 ( Pt 5):393-400.2573311
Sahm DF, Murray JL, Munson PL, Nordquist RE, Lerner MP. Gamma-glutamyltranspeptidase levels as an aid in the management of human cancer. Cancer. 1983;52(9):1673-1678.6137275
Woodruff SA, Sontag MK, Accurso FJ, Sokol RJ, Narkewicz MR. Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen. J Cyst Fibros. 2017;16(1):139-145.27555301
Yang MH, Chen TH, Wang SE, et al. Biochemical predictors for absence of common bile duct stones in patients undergoing laparoscopic cholecystectomy. Surg Endosc. 2008;22(7):1620-1624.18000708
Young, DS. Effects of Drugs on Clinical Laboratory Tests, 5th ed, Volume 1: “Listing by Test”. AACC Press, American Association of Clinical Chemistry. 2000; Section 3, pp. 374-9.
Alias
- Gamma glutamyl transpeptidase
Test Setup Days
Monday through Friday PM shift
CPT
82977 Limited Coverage Test For Medicare.
Advance Beneficiary Notice Of Non-Coverage (ABN) Required
If Diagnosis Not Covered.
LOINC: 2324-2
Reference Range
MALE: <60 U/L
FEMALE: <40 U/L
| UNIT CODE | UNIT CODE NAME | ANALYTE | GENDER | AGE | REFERENCE RANGE | Units of Measure |
|---|---|---|---|---|---|---|
| 2216 | GGTP | GGT | NOT SPECIFIED | ALL | <60 | U/L |
| 2216 | GGTP | GGT | MALE | ALL | <60 | U/L |
| 2216 | GGTP | GGT | FEMALE | ALL | <40 | U/L |