From the Guidelines
When a patient presents with elevated alkaline phosphatase (ALP), additional laboratory tests should include liver function tests (AST, ALT, GGT, bilirubin), ALP isoenzymes, calcium, phosphorus, parathyroid hormone (PTH), vitamin D levels, and a complete blood count. These tests help differentiate between hepatobiliary and bone sources of elevated ALP. Gamma-glutamyl transferase (GGT) is particularly useful as it rises in liver disease but not in bone disorders 1. If liver pathology is suspected, further testing should include hepatitis serologies, abdominal ultrasound, and potentially MRCP or ERCP to evaluate the biliary system. For suspected bone disorders, consider bone-specific ALP, bone scans, or skeletal surveys. Medication review is essential as certain drugs can elevate ALP 1.
Some key points to consider when evaluating elevated ALP include:
- The pattern of abnormalities guides diagnosis - for example, elevated ALP with normal transaminases suggests cholestatic liver disease or bone pathology, while concurrent elevation of transaminases points toward hepatocellular injury.
- In elderly patients or those with unexplained weight loss, cancer markers like CEA and CA 19-9 may be appropriate to screen for malignancies that can cause ALP elevation.
- Fractionating alkaline phosphatase into its liver, bone, and intestinal isoenzyme fractions can also be very informative 1.
- Glutamate dehydrogenase (GLDH) is a mitochondrial enzyme which can provide further supporting evidence that aminotransferase elevations are of hepatic origin, also potentially indicating hepatic mitochondrial injury 1.
It is crucial to monitor liver tests regularly, especially in patients undergoing treatment with potentially hepatotoxic drugs, and to consider the potential for delayed liver injury 1.
From the Research
Additional Lab Tests for Elevated Alkaline Phosphatase
To further evaluate a patient with elevated alkaline phosphatase (ALP), the following lab tests can be ordered:
- Gamma glutamyl transferase (GGT) to confirm the hepatic origin of the ALP elevation 2
- Abdominal ultrasound to evaluate the biliary system and distinguish between extrahepatic (biliary obstruction) or intrahepatic (primary biliary cholangitis, primary sclerosing cholangitis, etc.) cholestasis 2
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to assess for hepatocellular injury 3, 4
- Bilirubin levels, including fractionation to direct and indirect bilirubin fractions, to evaluate for hepatocellular disease or biliary obstruction 2, 4
- Testing for viral hepatitis A, B, and C, nonalcoholic fatty liver disease, alcoholic liver disease, hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency to evaluate for hepatocellular injury 4
- Testing for primary biliary cholangitis and primary sclerosing cholangitis to evaluate for cholestatic injury 4
- Serum albumin and prothrombin levels to evaluate hepatic function 2
Rationale for Additional Lab Tests
The additional lab tests are ordered to: