Gamma-glutamyl transferase (GGT) is significantly elevated in a patient on long-term phenytoin therapy, but serum bilirubin, ALT, and ALP from bone are normal. The mechanism for this selective GGT elevation is:

• A Hepatocyte necrosis releasing cytosolic GGT
• B Decreased renal clearance of GGT
• C Enzyme induction of microsomal GGT by phenytoin ✓
• D Cholestasis causing biliary GGT release

Explanation

Phenytoin (and other anticonvulsants, as well as alcohol) induces hepatic microsomal enzymes including GGT via activation of pregnane X receptor (PXR) or constitutive androstane receptor (CAR). This causes transcriptional upregulation of GGT gene expression, resulting in elevated serum GGT without hepatocellular necrosis or cholestasis. This is the basis for using GGT as a marker of alcohol use and of enzyme-inducing drug exposure. ALT and ALP (bone) remain normal because hepatocyte integrity is preserved.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.