From the Guidelines
The evaluation of elevated alkaline phosphatase (ALP) should begin with determining the source of elevation through additional laboratory testing, including gamma-glutamyl transferase (GGT), 5'-nucleotidase, and fractionation of ALP isoenzymes to distinguish between hepatic and bone origins, as recommended by the most recent guidelines 1. The initial workup should include a comprehensive history and physical examination, focusing on symptoms of liver disease, bone disorders, pregnancy, or medication use.
- For hepatobiliary causes, obtain liver function tests (AST, ALT, bilirubin), hepatitis serologies, and imaging studies such as ultrasound, CT, or MRCP.
- For bone-related elevations, consider calcium, phosphorus, vitamin D levels, and bone-specific ALP. Management depends on the underlying cause:
- for hepatobiliary disease, treat the primary condition (e.g., ursodeoxycholic acid for primary biliary cholangitis, 13-15 mg/kg/day) 1.
- for bone disorders, address the specific condition (e.g., bisphosphonates for Paget's disease). Isolated ALP elevations less than three times the upper limit of normal without symptoms may be monitored with repeat testing in 2-3 months, as suggested by previous studies 1. ALP elevations occur due to increased production or release from affected tissues, with the liver and bone being the primary sources in adults, while intestinal and placental sources may contribute in specific circumstances, as noted in the most recent guidelines 1.
From the Research
Evaluation of Elevated Alkaline Phosphatase (ALP) Levels
Elevated ALP levels can be caused by a variety of conditions, including bone and liver diseases. The evaluation and management approach for elevated ALP levels involves identifying the underlying cause of the elevation.
Common Causes of Elevated ALP Levels
- Bone involvement from malignancy or Paget's disease 2
- Sepsis, including gram-negative and gram-positive organisms, and fungal sepsis 2, 3
- Biliary obstruction, including malignant obstruction and common bile duct stones 2
- Acquired immunodeficiency syndrome (AIDS) 2
- Diffuse liver metastases 2
- Benign intrahepatic disease, including liver hemangiomas, sarcoid hepatitis, and drug-induced cholestasis 2
- Underlying malignancy, including infiltrative intrahepatic malignancy and bony metastasis 4
- Bone disease, including osteomalacia and Paget's disease 4
- Unsuspected parenchymal liver disease, including non-alcoholic fatty liver disease and viral hepatitis 4
Diagnostic Approach
The diagnostic approach for elevated ALP levels involves a combination of clinical evaluation, laboratory tests, and imaging studies. The goal is to identify the underlying cause of the elevation and to rule out other potential causes.
- Clinical evaluation: A thorough medical history and physical examination are essential in evaluating patients with elevated ALP levels 2, 4
- Laboratory tests: Additional laboratory tests, such as liver function tests, bone alkaline phosphatase, and tumor markers, may be ordered to help identify the underlying cause of the elevation 2, 4
- Imaging studies: Imaging studies, such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), may be ordered to evaluate the liver, bones, and other organs for potential causes of the elevation 2, 4
Management
The management of elevated ALP levels depends on the underlying cause of the elevation. Treatment may involve addressing the underlying condition, such as treating a bacterial infection or managing a malignancy.
- Treatment of underlying condition: The underlying condition causing the elevated ALP levels should be treated accordingly 2, 4
- Monitoring: Patients with elevated ALP levels should be monitored regularly to assess for resolution of the elevation and to rule out progression of the underlying condition 2, 4