Marker Name: GGT
REFERENCE RANGES FOR GGT:
Laboratory reference range:
Male and female: 0–65 IU/L
Functional reference ranges:14
Male: 0–29 IU/L
Female: 0–21 IU/L
DESCRIPTION:
Gamma-glutamyl transpeptidase (GGT) is an enzyme that transfers a gamma-glutamyl moiety to an amino acid acceptor. It is an enzyme in the gamma-glutamyl cycle, which participates in glutathione drug detoxification and amino acid transport.1,2 Glutathione is the most abundant substrate for GGT.3
GGT is primarily found in the hepatobiliary tract, kidney, pancreas, and liver.4,5 The enzyme is also present in the spleen, heart, brain, and seminal vesicles to a lesser extent.6 The highest concentration of GGT in the body is in the kidneys, but the enzyme present in serum is primarily produced by the liver.7,8
Like alkaline phosphatase, GGT levels increase in the blood subsequent to hepatobiliary obstruction.5 Unlike alkaline phosphatase, however, GGT is not found in appreciable levels in bone. Therefore, it can be used to clarify the source of increased alkaline phosphatase levels in blood.4,9 That is, elevated alkaline phosphatase and GGT levels in the serum indicate hepatobiliary disease, while alkaline phosphatase without a corresponding increase in GGT suggests a disease affecting the bone.10
Certain forms of gammopathy (e.g., type IgM Waldenstrom’s macroglobulinemia) may interfere with the performance of the clinical assay.7 GGT is a sensitive test; it is abnormal in virtually all patients with liver disease regardless of cause.3 On the other hand, GGT has poor specificity, since it is increased in many conditions.
Increased GGT is believed to result from spillage from cell membranes when the source tissue is damaged (e.g., liver injury subsequent to excessive alcohol intake) or from increased enzyme production (e.g., induction by anticonvulsants).3 The highest levels of serum GGT tend to occur in cases of hepatobiliary obstruction.10 Anticonvulsants of various drug classes are well known to create serum GGT elevations.11 Drug-induced elevations in GGT are believed to be induced by relative decreases in glutathione levels in the liver. As the liver attempts to detoxify and excrete various drugs, especially anticonvulsants, glutathione needs increase. Interestingly, when glutathione levels are normalized through cysteine supplementation, the offending drugs do not induce a rise in GGT levels.12
Abnormally low levels of GGT in the serum are generally not of clinical concern. Protein malnutrition, particularly a deficiency in amino acids that contain sulfur, could lower serum GGT levels, as has been shown experimentally in rodents.13 Even under these conditions, however, GGT levels return to normal after protein has been restored.
PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:
High in:3,15
- Diabetes
- Obesity
- Excessive alcohol intake
- Smoking
- Biliary obstruction
- Liver disease
- Liver injury
- Pancreatitis
- Cardiovascular disease (e.g., hypertension, congestive heart failure)
- Genetic abnormality (rare)
- Drugs
- Phenytoin
- Carbamazepine
- Barbiturates (e.g., phenobarbital)
- NSAIDs
- Statins
- Antibiotics/antifungals
- H2 histamine receptor antagonists
Low in:3
- Low-protein diet
- Genetic GGT deficiency (rare)
- Drugs
- Clofibrate
- Oral contraceptives
FUNCTIONAL RANGE INDICATIONS:
High in:
- Iron overload
- Metabolic dysfunction (dysglycemia, insulin resistance, etc.)
Low in:
- Same as conventional indications
References:
- http://www.ncbi.nlm.nih.gov/pubmed/1378736
- http://www.ncbi.nlm.nih.gov/pubmed?term=4152527
- http://dx.doi.org/10.1080/20014091084227
- http://www.sciencedirect.com/science/article/pii/0009898169903829
- http://www.clinchem.org/content/24/6/905.abstract
- http://www.ncbi.nlm.nih.gov/pubmed?term=6104563
- http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8677
- http://dx.doi.org/10.1016/0005-2744(77)90006-7
- http://www.clinchem.org/content/18/4/358.abstract
- http://www.clinchem.org/content/15/2/124.abstract
- http://www.ncbi.nlm.nih.gov/pubmed/?term=6113134
- http://www.ncbi.nlm.nih.gov/pubmed/?term=2576915
- http://www.ncbi.nlm.nih.gov/pubmed/?term=10347814
- http://www.ncbi.nlm.nih.gov/pubmed/21418268
- https://labtestsonline.org/understanding/analytes/ggt/tab/test/