Diagnosis:
Diagnostic use of alkaline phosphatase and γ-glutamyl transpeptidase (GGT)
• Alkaline phosphatase (ALP) is a hydrolase enzyme produced in liver, bone, kidney, intestine, and placenta. It is most commonly elevated in liver or bone disease. In the liver, the enzyme is found on the canalicular surface of hepatocytes, and therefore elevated ALP indicates biliary obstruction, cholestasis, or space-occupying lesions. Bone ALP is produced by osteoblasts and is elevated in Paget’s disease, metastatic tumors, and metabolic bone disease, among others.
• ALP isoenzymes can be separated by electrophoresis to distinguish the tissue of origin. In addition, heat fractionation can be used to distinguish the tissue source, with placental ALP being the most heat resistant and bone ALP being the most heat labile. Liver-derived ALP is moderately stable. Remember, “bone burns.”
• Placental ALP is known as Regan isoenzyme and is known to be produced by a number of malignancies, including germ cell and urinary tract tumors. Regan isoenzyme is heat stable.
• Both γ-glutamyl transpeptidase (GGT) and 5′-nucleotidase help distinguish between an elevated ALP caused by liver versus bone disease and generally may be used interchangeably. However, GGT is also associated with chronic alcohol use and alcoholic liver disease. Therefore, in this case, given that both the elevated ALP and GGT can be explained by other underlying conditions (Paget’s disease and alcoholism, respectively), further laboratory evaluation for hepatobiliary disease is warranted, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, and prothrombin time.
• The presence of gallstones puts the patient at risk for extrahepatic biliary obstruction, which would result in increased conjugated (direct) bilirubin rather than unconjugated (indirect) bilirubin. Alcoholic liver disease and cirrhosis can also result in increased conjugated bilirubin. Obstruction caused by gallstones would result in elevated ALP, 5´-nucleotidase, and GGT with or without mild elevation in ALT and AST.
• Patients with cirrhosis of any cause often have normal or decreased levels of AST and ALT because ongoing hepatocyte injury is absent. However, the abnormal liver architecture of cirrhosis can result in regional intrahepatic obstruction of bile flow, resulting in elevated ALP, GGT, and 5´-nucleotidase.