From the Guidelines
The appropriate workup for an elevated alkaline phosphatase (ALP) level should begin with a thorough history and physical examination, followed by targeted laboratory testing to determine the source of elevation, as recommended by the most recent guidelines 1. The initial step is to repeat the ALP measurement to confirm the elevation and order fractionation to distinguish between liver and bone isoenzymes.
- For suspected hepatobiliary causes, order liver function tests including AST, ALT, GGT, bilirubin, and albumin, as these tests can help identify liver pathology and guide further evaluation 1.
- If liver pathology is suggested, obtain abdominal ultrasound to evaluate for biliary obstruction, hepatic lesions, or gallbladder disease, as this imaging modality is useful for assessing the biliary tree and liver structure 1.
- For suspected bone origin, check calcium, phosphorus, parathyroid hormone, and vitamin D levels, and consider bone-specific ALP, as these tests can help identify bone-related disorders that may be causing the elevated ALP 1. Additional testing may include hepatitis serologies, autoimmune markers (ANA, anti-mitochondrial antibodies), and imaging studies such as MRCP or ERCP for biliary evaluation, as these tests can help identify specific causes of liver injury or biliary obstruction 1. If initial workup is inconclusive, consider bone scan, CT, or MRI depending on clinical suspicion, as these imaging modalities can provide further information on bone or liver pathology 1. Remember that certain medications, pregnancy, and growing children can cause benign ALP elevations, and a thorough medical history and physical examination can help identify these benign causes 1. The systematic approach is important because ALP elevations can indicate various conditions ranging from benign (pregnancy, bone growth) to serious (malignancy, biliary obstruction) across multiple organ systems, primarily liver and bone 1.
From the Research
Elevated Alkaline Phosphatase Workup
Elevated alkaline phosphatase (ALP) levels can indicate various conditions, including bone or liver disease, neoplasms, or benign conditions such as pregnancy. The appropriate workup for elevated ALP levels involves determining the source of the increased enzyme activity.
Possible Causes
- Bone disease: Elevated ALP levels can be associated with bone conditions such as ankylosing spondylitis 2 or hypophosphatasia.
- Liver disease: ALP isoenzyme studies can indicate an increased liver fraction in patients with elevated ALP levels 2.
- Pregnancy: ALP levels can be elevated during pregnancy, particularly in the third trimester, due to the production of placental ALP 3.
- Benign conditions: Benign familial hyperphosphatasemia is a rare condition characterized by elevated ALP levels due to increased intestinal ALP activity 4.
Diagnostic Approach
- ALP isoenzyme studies: These studies can help determine the source of the increased ALP activity, such as liver, bone, or intestinal ALP 4, 2, 5.
- Imaging studies: Imaging studies such as X-rays, CT scans, or MRI scans may be necessary to evaluate bone or liver disease.
- Laboratory tests: Additional laboratory tests, such as liver function tests or bone turnover markers, may be necessary to evaluate the underlying cause of elevated ALP levels.
Importance of Isoenzyme Studies
- ALP isoenzyme studies are essential in determining the source of elevated ALP activity, as different isoenzymes are associated with different tissues or conditions 5.
- High-performance affinity chromatography (HPAC) is a sensitive and specific method for separating liver and bone ALP isoenzymes in human serum 5.