What Are the Reasons for an Elevated Alkaline Phosphatase?

Margaret (Peg) A. Fitzgerald, MS, APRN, BC, NP-C, FAANP


April 27, 2000


I sometimes see an elevated phosphatase level when monitoring liver function tests for a statin protocol. What are the reasons for an elevated phosphatase level? When should I stop monitoring a persistently elevated, but stable, alkaline phosphatase?


Margaret A. Fitzgerald, MS, APRN, BC, NP-C, FAANP
President, Fitzgerald Health Education Associates, Inc., North Andover, Massachusetts; family nurse practitioner, Greater Lawrence (Massachusetts) Family Health Center; Visiting Professor, University of Massachusetts, Worcester.

The term "liver function tests" is often used to describe a panel of laboratory measures of a variety of hepatic enzymes, including serum aminotransferase (aspartate aminotransferase or AST and alanine aminotransferase or ALT) and alkaline phosphatase (ALP). Rather than a measure of hepatic function, these tests evaluate hepatocyte integrity, as serum levels of these enzymes rise in response to a variety of forms of injury to hepatic cells.

Abnormal levels of hepatic enzymes including ALP may be found in up to 6% of well adults, whereas liver disease will be found only in about 1% of the general population. This likely reflects the fact that what is considered the acceptable range of values for ALP and other hepatic enzymes reflects a population-based norm; outliers without significant disease should be expected. In addition, minor ALP elevation often occurs because of improper handling of specimen and delayed testing. ALP may increase in a sample by as much as 5% to 10% after 4 hours of storage. A clinically evident cause is usually noted with marked ALP elevation (> 3 times upper limit of normal [ULN]).

In addition to being found in the liver, ALP is found in abundance in other tissue, including the placenta, bone, and intestinal mucosa. Rapid growth in or injury to these tissues causes an elevation in total ALP. Placental ALP fraction influences the high ALP measures found during pregnancy. Childhood ALP measures are often up to 3 times those of adult levels, influenced by bone growth and high levels of this ALP fraction.

Total ALP elevation due to the hepatic fraction is a sensitive indicator of intra- or extrahepatic cholestasis. ALP measurement at up to 2 times ULN is found in hepatitis and heavy alcohol consumption. Marked ALP elevation is usually noted with extrahepatic biliary obstruction, primary biliary cirrhosis, and infiltrative processes such as neoplasm. Less dramatic ALP elevation can be seen in infectious mononucleosis, bile duct obstruction, hepatitis, heavy alcohol consumption, and fatty liver.

When an abnormal ALP is noted, the nurse practitioner needs to assess the degree of elevation. If a minor elevation is noted in an otherwise well adult with normal biochemical markers, a repeat measurement should be considered. If this is within normal limits, ongoing monitoring and a repeat measure in 6-12 months is reasonable.

If the abnormal result is confirmed in repeat measurement, obtaining a serum gamma glutamyl transferase (GGT) is a helpful next step. Found primarily in the liver and kidney, GGT rise usually parallels changes in ALP in liver disease; elevations in both ALP and GGT help confirm the likelihood of a hepatic disorder. Common causes of minor ALP elevation in the asymptomatic adult primary include drug or alcohol-induced liver disease and fatty liver. ALP should return to normal within 2-8 weeks of the withdrawal of the offending drug or discontinuation of alcohol use. With continued alcohol use, the NP should anticipate that ALP remains persistently elevated but usually does not exceed 3 times ULN. Changes seen in fatty liver should resolve with weight loss. Without weight loss, ALP levels will not change but should not rise markedly. In either situation, elevation beyond that level should trigger a new evaluation for its cause. If GGT is normal when ALP elevation is noted, evaluation for bone disease, included bony metastases, should be pursued.

ALP measurement should be limited to the evaluation of select clinical conditions and not measured as part of routine monitoring during use of the commonly prescribed medications such as the statins (HMG CoA reductase inhibitors) or the glitazones; periodic measurement of AST and ALT, respectively, is sufficient. Focusing laboratory monitoring during the use of these therapeutic agents will help lower healthcare costs and limit the need to evaluate minor and clinically insignificant ALP elevation.


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