From the Guidelines
The workup for elevated alkaline phosphatase (ALP) should begin with a thorough history and physical examination, followed by targeted laboratory testing to determine the source, with the most recent and highest quality study suggesting fractionation of ALP and measurement of GGT to indicate whether the elevation is of hepatic or nonhepatic origin 1.
Initial Steps
- Order fractionation of ALP to distinguish between bone, liver, intestinal, or placental origin
- Measure GGT to help confirm the source of elevated ALP, as concomitantly elevated GGT can indicate a hepatic origin 1
- Obtain liver function tests including AST, ALT, bilirubin, and albumin if liver pathology is suspected
Liver Pathology
- If liver etiology is suspected, proceed with hepatitis serologies, abdominal ultrasound, and possibly MRCP or ERCP to evaluate for biliary obstruction 1
- Consider the diagnosis of primary sclerosing cholangitis (PSC) in patients with elevated serum markers of cholestasis and typical findings on high-quality cholangiography 1
Bone Pathology
- For bone-origin ALP, order calcium, phosphorus, PTH, and vitamin D levels, followed by bone imaging such as skeletal survey or bone scan
Additional Testing
- Additional testing may include TSH for hyperthyroidism, pregnancy testing in women of childbearing age, and evaluation for malignancy with age-appropriate cancer screening
- Medication review is essential as certain drugs can elevate ALP 1
Referral
- Persistent unexplained elevation warrants referral to a gastroenterologist, hepatologist, or endocrinologist depending on the suspected source The pattern and degree of elevation often provide clues to the underlying cause, with isolated ALP elevation suggesting bone disease and elevation with other liver enzymes pointing toward hepatobiliary disease 1.
From the Research
Workup for Elevated Alkaline Phosphatase (Alk Phos)
The workup for elevated alkaline phosphatase (alk phos) involves several steps to determine the underlying cause of the elevation. Some possible causes of elevated alk phos include:
- Hepatobiliary diseases, such as choledocholithiasis, which can cause elevations in alk phos levels out of proportion to aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2
- Bone diseases, such as those that affect bone mineralization, where alk phos plays a crucial role 3
- Transient hyperphosphatasemia (THP) of infants and children, which is a benign condition that requires no intervention 4
- Obesity, which has been linked to higher levels of total and liver alk phos 5
Diagnostic Approach
The diagnostic approach for elevated alk phos may involve:
- Measuring the levels of AST and ALT to determine if the elevation is due to hepatobiliary disease 2
- Assessing for symptoms of gastrointestinal, hepatobiliary, or bone disease 4
- Evaluating anthropometric variables, such as body mass index and waist circumference, which may be related to alk phos levels 5
- Using a semi-automated flow injection-bead injection system to selectively assay bone alkaline phosphatase (BALP) 6
- Considering the patient's age, medical history, and other laboratory results to determine the underlying cause of the elevation 4, 3