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Gamma Glutamyltransferase

Gamma glutamyltransferase (GTT) is a membrane-bound peptidase that hydrolyzes peptides to amino acids and smaller peptides. It is found in proximal renal tubule, liver, pancreas and intestine. GGT activity in serum comes primarily from liver. The circulating half-life is 7 to 10 days. However, the half-life increases to 28 days in alcohol-associated liver injury, suggesting impaired clearance.

Several factors affect GGT, other than liver injury.

  • GGT activity can fluctuate between 10 and 15% from day to day.
  • GGT activity decreases immediately after eating.
  • GGT activity is 25 to 50% higher in obese individuals.
  • GGT activity is 10% higher in individuals smoking 1 pack per day & doubles with heavier smoking.
  • GGT activity is approximately 2 fold higher in healthy African Americans.
  • GGT activity decreases 25% during early pregnancy.

GGT is most useful in determining the cause of elevated alkaline phosphatase and as a marker of chronic alcohol consumption. GGT is a useful adjunct to determine the origin of elevated alkaline phosphatase activity, because it is elevated by liver disease, but not bone disease.

GGT

ALP

Diagnosis

Normal

Elevated

Bone disease

Elevated

Elevated

Liver disease

GGT is not very useful in the differential diagnosis of liver disease. The highest GGT levels are seen in cholestatic liver disease; levels are typically more than 5 to 12 times the upper limit of normal and rise in parallel with alkaline phosphatase. GGT typically rises during the first week of viral hepatitis, peaks at 5 times the upper limit of normal during the second or third week, and remains elevated up to six weeks. GGT levels are also elevated in hepatoma, liver metastases, chronic active hepatitis, alcoholic hepatitis, extrahepatic obstruction, intrahepatic cholestasis, and inactive cirrhosis. GGT levels do not correlate with the severity of liver disease.

GGT is particularly sensitive to alcohol consumption and may be elevated even when other liver function tests remain normal. However, liver biopsies in patients with solitary GGT elevations seldom show irreversible hepatic injury. Social drinking does not elevate GGT, but chronic alcohol consumption induces the synthesis of GGT more than alkaline phosphatase. A GGT: ALP ratio of >5:1 favors a diagnosis of alcoholic liver disease.

Pancreatitis also causes moderate elevations in GGT activity. Patients with diabetes, hyperthyroidism, rheumatoid arthritis, and obstructive pulmonary disease often have an increased GGT, but the reason for this elevation is unknown.

Many drugs increase GGT levels up to 2 times the upper limit of normal. Examples include:

  • Acetaminophen
  • Carbamazepine
  • Cimetidine
  • Coumadin
  • Furosemide
  • Heparin
  • Isotretinoin
  • Methotrexate
  • Phenobarbital
  • Testosterone
  • Tricyclic antidepressants
  • Valproic acid

Phenytoin may cause levels to increase 5 fold. Oral contraceptives can decrease GGT concentration.

Reference range is 15 to 80 IU/L. Specimen requirement is one red top tube of blood.

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