What labs should be ordered for elevated alkaline phosphatase (ALP)?

Diagnostic Approach for Elevated Alkaline Phosphatase

For elevated alkaline phosphatase (ALP), you should order GGT, other liver enzymes (AST, ALT, bilirubin), and consider bone-specific ALP isoenzyme testing if the source remains unclear after initial workup. 1

Initial Laboratory Workup

When evaluating elevated ALP, a systematic approach is essential to determine the source (liver vs. bone) and underlying etiology:

1. First-line tests:

   • Gamma-glutamyl transferase (GGT) - helps distinguish between liver and bone sources 1, 2, 3
   • Complete liver panel:
     • Aspartate aminotransferase (AST)
     • Alanine aminotransferase (ALT)
     • Total and direct bilirubin
     • Albumin

2. If GGT is normal:

   • Consider bone source of ALP elevation 3
   • Order bone-specific ALP isoenzyme testing 1, 4
   • Consider calcium, phosphate, parathyroid hormone (PTH), and vitamin D levels

3. If GGT is elevated:

   • Liver source is more likely 2, 4
   • Consider 5'-nucleotidase (to calculate GGT/5'-nucleotidase ratio for differentiating intrahepatic vs. extrahepatic cholestasis) 1

Imaging Studies

Based on initial laboratory results:

• For suspected liver/biliary source:

  • Abdominal ultrasound (first-line imaging) 1
  • If ultrasound is inconclusive: MRCP (magnetic resonance cholangiopancreatography) 1
  • Consider CT scan or MRI for detailed liver assessment if needed 1

• For suspected bone source:

  • Bone-specific imaging based on clinical presentation

Important Clinical Considerations

• Recent research shows that isolated elevated ALP is commonly associated with malignancy (57%), particularly infiltrative intrahepatic malignancy and bony metastasis 5
• Bone disease accounts for approximately 29% of cases with isolated elevated ALP 5
• GGT measurement is crucial but not infallible - it wrongly identified the source of ALP elevation in 3 of 28 patients in one study, highlighting the importance of bone isoenzyme testing in unclear cases 4

Common Pitfalls to Avoid

1. Overreacting to minimally elevated ALP: For minimally elevated ALP without symptoms, monitoring with repeat testing in 3-6 months is appropriate 1

2. Missing malignancy: An isolated elevated ALP of unclear etiology is significantly associated with metastatic disease and carries a poor prognosis (47% mortality within an average of 58 months) 5

3. Relying solely on GGT: While GGT is useful for distinguishing liver from bone sources, it is not perfectly accurate. Consider bone-specific ALP isoenzyme testing in unclear cases 1, 4

4. Forgetting rare causes: Consider conditions like transient hyperphosphatasemia in children, primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis 1, 3

By following this systematic approach, you can efficiently determine the source and underlying cause of elevated ALP, leading to appropriate management and improved patient outcomes.