From the Guidelines
Elevated alkaline phosphatase (ALP) levels in the blood require immediate medical evaluation to determine the underlying cause, as it can indicate issues with the liver, bones, or other organs, and the treatment will depend entirely on the underlying condition causing the elevation. The causes of elevated ALP can be diverse, including liver diseases (like hepatitis, cirrhosis, or bile duct obstruction), bone disorders (such as Paget's disease, bone metastases, or healing fractures), pregnancy, certain medications, or other conditions like hyperthyroidism or intestinal inflammation 1. According to the most recent guidelines, if ALP is elevated, measurements of gamma-glutamyl transpeptidase (GGT) can help indicate whether the elevation is of hepatic or nonhepatic origin, as GGT is found in the liver and other organs but not in bone 1.
Key Considerations
- Elevated ALP levels can be due to a variety of conditions, and thus, a thorough diagnostic approach is necessary to identify the underlying cause.
- The normal range for ALP in adults is typically 20-140 IU/L, though this can vary by laboratory and age.
- Conditions such as choledocholithiasis, malignant obstruction, biliary strictures, and infections can cause extrahepatic biliary obstruction and elevated ALP of liver origin 1.
- Infiltrative liver diseases, such as sarcoidosis, amyloidosis, and hepatic metastases, may also lead to intrahepatic cholestasis and elevated ALP 1.
Diagnostic Approach
- Initial steps should include a review of the patient's clinical history and medications.
- Imaging of the biliary tree may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis, especially if the liver is suspected to be the source of elevated ALP 1.
- Additional tests such as liver function tests, bone-specific ALP measurements, or possibly a biopsy may be ordered by a healthcare provider to further investigate the cause of elevated ALP.
Treatment
- The treatment will depend entirely on the underlying condition causing the elevation of ALP.
- For example, if the elevation is due to a medication, stopping that medication may resolve the issue; if it's due to a bile duct obstruction, surgery might be necessary.
- It is crucial to consult a healthcare provider for personalized advice and treatment, as the management of elevated ALP is highly dependent on the specific cause and the patient's overall health condition.
From the Research
Causes of Elevated Alkaline Phosphatase
- Elevated alkaline phosphatase (ALP) levels can be caused by various conditions, including underlying malignancy, bone disease, unsuspected parenchymal liver disease, non-malignant infiltrative liver disease, and other disorders 2.
- A study found that the most common cause of ALP elevation was due to underlying malignancy (57%), followed by bone disease (29%) 2.
- Another study noted that ALP can also originate in the intestine and placenta, and that very few cases of persistent elevations of ALP have been reported in the literature without underlying pathology 3.
Diagnostic Approach
- The diagnostic workup of a patient with elevated ALP levels can be quite costly, and in some cases, elevated ALP is benign, requiring no intervention 4.
- An algorithm can be utilized as a guide in a primary care setting to arrive at the diagnosis of transient hyperphosphatasemia (THP) and avoid further tests or referrals 4.
- For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken 5.
Clinical Significance
- An isolated, elevated ALP of unclear etiology is associated with several very specific and important disorders, in particular metastatic intrahepatic malignancy 2.
- Providers should be aware of the potential clinical significance of an elevated ALP, as it can be a marker of underlying disease 2.
- Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions, and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings 5.