What is the appropriate workup for a patient with elevated alkaline phosphatase (alk phos)?

Workup for Elevated Alkaline Phosphatase

The first step in evaluating elevated alkaline phosphatase (ALP) should be to confirm its hepatobiliary origin by measuring gamma-glutamyl transferase (GGT) and/or performing alkaline phosphatase isoenzyme fractionation. 1

Step 1: Confirm Source of Elevated ALP

• Measure GGT and/or perform ALP isoenzyme fractionation to determine if the elevated ALP is of hepatobiliary origin 1
• Consider 5'-nucleotidase testing as an alternative marker of hepatobiliary origin 2, 1
• ALP can originate from liver, bone, intestine, or other tissues, so determining the source is critical for appropriate workup 3, 4

Step 2: Initial Clinical Assessment and Laboratory Testing

• Review medication history for potential drug-induced causes of ALP elevation 2, 1
• Obtain additional liver function tests including:
  • Aminotransferases (ALT, AST) to assess for hepatocellular injury 2
  • Total and direct bilirubin to evaluate for cholestasis 2, 1
  • Complete blood count to assess for underlying systemic conditions 2
  • Albumin and prothrombin time to evaluate liver synthetic function 1

Step 3: Imaging Studies

• Abdominal ultrasound should be performed as the initial imaging study to evaluate for biliary obstruction and parenchymal liver disease 1
• For patients with malignant renal masses, elevated ALP warrants bone scan evaluation due to increased risk of metastatic disease (approximately 10% when ALP is elevated) 2
• In patients with breast cancer, abdominal imaging using diagnostic CT or MRI is indicated with elevated ALP 2

Step 4: Disease-Specific Workup

• If hepatobiliary origin is confirmed:

  • Consider serologic testing for viral hepatitis and autoimmune markers 1
  • MR cholangiography or endoscopic retrograde cholangiography may be needed to evaluate for primary sclerosing cholangitis or biliary strictures 1
  • Liver biopsy may be necessary for persistently elevated ALP without clear cause 1

• If bone origin is suspected:

  • Bone scan is indicated, especially when clinical symptoms such as bone pain are present 2, 1
  • Consider evaluation for Paget's disease, bone metastases, or other metabolic bone disorders 5

• If malignancy is suspected:

  • CT chest/abdomen/pelvis to evaluate for primary malignancy or metastatic disease 1
  • Recent research shows malignancy (57%) is the most common cause of isolated elevated ALP of unclear etiology, with 47% mortality within an average of 58 months 6

Important Clinical Considerations

• Extremely high ALP levels (>1000 U/L) are most frequently associated with sepsis, malignant biliary obstruction, and AIDS 5
• Patients with sepsis can present with markedly elevated ALP despite normal bilirubin levels 5
• Benign familial hyperphosphatasemia is a rare cause of elevated ALP that should be considered when other causes are excluded 3
• For oncology patients, ALP should be monitored before each treatment cycle or at least monthly 2
• In patients with renal cell carcinoma, elevated ALP is a significant predictor of bone metastases and should prompt bone scan evaluation 2