From the Guidelines
When alkaline phosphatase (ALP) is elevated but isoenzymes are normal, the most appropriate initial step is to conduct a comprehensive review of the patient's medication list and medical history to identify potential causes of the elevation, as this pattern can occur in conditions affecting multiple organs simultaneously, such as systemic diseases, certain medications, or inflammatory conditions 1.
Key Considerations
- The elevation of ALP can be due to various conditions, including cholestatic liver disease, bone disease, or other systemic diseases, and a thorough evaluation is necessary to determine the underlying cause 1.
- The measurement of gamma-glutamyl transferase (GGT) can help indicate whether the elevated ALP is of hepatic or nonhepatic origin, as GGT is found in the liver and other organs but not in bone 1.
- Imaging studies of the liver and biliary system may be necessary to determine the etiology of extrahepatic or intrahepatic cholestasis if the liver is suspected to be the source of elevated ALP 1.
Diagnostic Approach
- Initial testing should include liver function tests, GGT, and imaging studies of the liver and biliary system to evaluate for potential liver or biliary disease 1.
- If these tests are unremarkable, consider bone-specific causes with vitamin D levels and bone scans, as ALP can also be elevated in bone disease such as Paget's disease or bony metastases 1.
- Serial monitoring of ALP levels over 4-6 weeks is recommended to determine if the elevation is transient or persistent, and to guide further management and evaluation 1.
Clinical Significance
- The elevation of ALP can have significant clinical implications, as it can indicate underlying liver or biliary disease, bone disease, or other systemic conditions that require prompt evaluation and management 1.
- A thorough understanding of the potential causes of elevated ALP and a systematic approach to evaluation and management are essential to provide optimal patient care 1.
From the Research
Alkaline Phosphatase Isoenzymes
- Alkaline phosphatase (ALP) is a membrane-bound metalloenzyme that consists of a group of true isoenzymes, all glycoproteins, encoded for by at least four different gene loci: tissue-nonspecific, intestinal, placental, and germ-cell ALP 2
- The clinically relevant isoenzymes are sol-liver, Mem-liver, lipoprotein-bound liver, and Sol-intestinal ALP in liver diseases, and Sol-bone and Anch-bone ALP in bone diseases 2
- Many different isoenzyme patterns can be found in malignancies and renal diseases 2
Elevated Alkaline Phosphatase with Normal Isoenzymes
- A normal total ALP activity does not rule out the presence of an abnormal isoenzyme pattern, particularly in children 2
- Separating ALP into its isoenzymes adds considerable value to the mere assay of total ALP activity 2
- In some cases, elevated alkaline phosphatase can be associated with hyperthyroidism, and the levels may not return to normal even after treatment until the euthyroid state is reached 3, 4, 5
Hyperthyroidism and Alkaline Phosphatase
- Abnormal liver function tests, including elevated alkaline phosphatase, are common in patients with hyperthyroidism 3, 4, 5
- The prevalence of alkaline phosphatase abnormalities in hyperthyroid patients was 25% 3, 44% 4, and 33% 5
- ATD therapy, along with euthyroidism restoration, was accompanied by normalization of LBT abnormalities, including alkaline phosphatase, in some cases 4