What are the follow-up tests for elevated alkaline phosphatase (ALP) levels?

From the Guidelines

Elevated alkaline phosphatase (ALP) levels should be followed up with gamma-glutamyl transferase (GGT) and 5'-nucleotidase tests to determine the source of ALP elevation, as recommended by the American College of Radiology 1. When evaluating elevated ALP levels, it is essential to consider the various organs that produce ALP, including the liver, bone, intestine, and placenta.

• Initial testing should include GGT and 5'-nucleotidase to help distinguish between hepatic and non-hepatic causes when elevated alongside ALP.
• Liver function tests, such as AST, ALT, bilirubin, and albumin, should be ordered to assess for liver disease.
• If liver pathology is suspected, imaging studies like ultrasound, CT scan, or MRI of the liver and biliary system are appropriate to evaluate for obstruction, masses, or inflammation.
• For suspected bone-related elevations, calcium, phosphate, parathyroid hormone (PTH), and vitamin D levels should be measured, potentially followed by bone scans or skeletal surveys. The selection of follow-up tests should be guided by the patient's clinical presentation, age, and other laboratory findings, as ALP elevations in children and pregnant women often reflect normal physiological processes rather than pathology, as noted in the study published in the Journal of the American College of Radiology 1.

From the Research

Follow-up Tests for Elevated Alkaline Phosphatase (ALP) Levels

Elevated ALP levels can be caused by various conditions, including liver disease, bone disease, and malignancies. To determine the underlying cause, several follow-up tests can be performed:

• Liver function tests, such as gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST) 2
• Bone-specific alkaline phosphatase (BAP) to assess bone turnover 3
• Imaging studies, such as ultrasound or computed tomography (CT) scans, to evaluate liver and bone morphology
• Tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), to screen for malignancies 4
• Electrophoresis to separate and identify different ALP isoenzymes, including liver (L-ALP), bone (B-ALP), and intestinal (I-ALP) isoenzymes 5, 2

Specific Conditions and Corresponding Tests

Certain conditions may require additional tests:

• Liver disease: Viral hepatitis panels, autoimmune liver disease panels, and liver biopsy 4, 2
• Bone disease: Bone density tests, such as dual-energy X-ray absorptiometry (DXA), and markers of bone turnover, such as N-telopeptide (NTx) and C-telopeptide (CTx) 3
• Malignancies: Imaging studies, such as positron emission tomography (PET) scans, and biopsies to confirm the presence of cancer 4, 5

Interpretation of Test Results

The results of these follow-up tests should be interpreted in the context of the patient's clinical presentation and medical history. For example:

• Elevated GGT and AST levels may indicate liver disease 2
• High BAP levels may suggest bone turnover 3
• Abnormal tumor marker levels may indicate the presence of a malignancy 4
• The presence of specific ALP isoenzymes may help diagnose certain conditions, such as liver or bone disease 5, 2