From the Guidelines
Elevated alkaline phosphatase (ALP) with normal fractional isoenzymes is most likely due to a generalized increase in ALP production, and management should focus on identifying potential causes through a thorough medication review and medical history, as recommended by the ACR Appropriateness Criteria for abnormal liver function tests 1. The pattern of normal fractional isoenzymes suggests a physiologic rather than pathologic process, but persistent unexplained elevations warrant comprehensive evaluation. Common causes of elevated ALP with normal fractional isoenzymes include certain medications, pregnancy, growth in adolescents, healing fractures, or certain metabolic disorders. When evaluating the patient, it is essential to consider the clinical history and medications, as well as the level of ALP elevation. If the patient is asymptomatic and the elevation is mild (less than 2-3 times the upper limit of normal), watchful waiting with repeat testing in 1-3 months may be appropriate, as outlined in the guidelines for abnormal liver function tests 1. For moderate to significant elevations, further investigation with imaging studies or additional laboratory tests may be necessary to rule out occult pathology, such as cholestatic liver disease or bone disease. The EASL clinical practice guidelines for sclerosing cholangitis also recommend risk assessment and sequential evaluation using non-invasive tests, including serum biochemistry and liver elastography 1. Key points to consider in the management of elevated ALP with normal fractional isoenzymes include:
- Thorough medication review and medical history
- Repeat testing in 1-3 months for mild elevations
- Further investigation with imaging studies or additional laboratory tests for moderate to significant elevations
- Consideration of non-invasive tests, such as liver elastography, for risk assessment and sequential evaluation.
From the Research
Alkaline Phosphatase Elevated with Normal Fractional Isoenzymes
- Elevated alkaline phosphatase levels can be caused by various factors, including bone and liver diseases 2, 3.
- In some cases, the intestinal fraction of alkaline phosphatase can be elevated, even in the absence of significant gastrointestinal pathology 2.
- The study by 2 highlights a case where a 32-year-old man had persistently elevated alkaline phosphatase levels, but normal liver and bone fractions, and a grossly elevated intestinal fraction.
- The estimation of specific alkaline phosphatase isoenzymes, such as liver and bone forms, can be valuable in diagnosing and monitoring certain diseases, including cancers 3.
- However, in cases where the fractional isoenzymes are normal, other factors such as benign biochemical findings should be considered 2.
- The changes in serum alkaline phosphatase levels can result from increased entry of enzyme into the circulation, due to increased osteoblastic activity in bone disease or increased synthesis of alkaline phosphatase by hepatocytes in hepatobiliary disease 3.