From the Guidelines
Elevated alkaline phosphatase (ALP) with normal gamma-glutamyl transferase (GGT) is nonspecific and can occur in various conditions, including bone disease, liver disease, and other disorders.
Evaluation of Elevated ALP with Normal GGT
To evaluate elevated ALP with normal GGT, the following steps should be taken:
- Clinical history and physical examination: A thorough clinical history and physical examination should be performed to identify any underlying conditions that may be causing the elevated ALP, such as bone disease, liver disease, or other disorders 1.
- Laboratory tests: Additional laboratory tests, such as liver function tests, complete blood count, and electrolyte panel, should be performed to rule out other causes of elevated ALP 1.
- Imaging studies: Imaging studies, such as ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI), may be necessary to evaluate the liver and biliary tree for any abnormalities 1.
Differential Diagnosis
The differential diagnosis for elevated ALP with normal GGT includes:
- Bone disease: Paget's disease, osteomalacia, or other bone disorders can cause elevated ALP 1.
- Liver disease: Primary biliary cholangitis, primary sclerosing cholangitis, or other liver disorders can cause elevated ALP 1.
- Other disorders: Other disorders, such as hypothyroidism or renal failure, can also cause elevated ALP 1.
Management
The management of elevated ALP with normal GGT depends on the underlying cause. If the cause is bone disease, treatment should be directed at the underlying bone disorder. If the cause is liver disease, treatment should be directed at the underlying liver disorder. If the cause is unknown, further evaluation and monitoring may be necessary to determine the underlying cause and develop an appropriate treatment plan 1.
From the Research
Evaluation of Elevated Alkaline Phosphatase with Normal Gamma-Glutamyl Transferase (GGT)
- Elevated alkaline phosphatase (ALP) with normal gamma-glutamyl transferase (GGT) can be seen in various conditions, including bone-related disorders and certain liver diseases 2.
- A study published in 2021 found that GGT activity has limited utility in assessing ALP elevations, with a sensitivity of 46.6% and specificity of 85.0% for hepatic ALP elevation 3.
- In cases where ALP is elevated and GGT is normal, further testing, such as ALP isoenzyme analysis, may be necessary to determine the source of the elevation 3, 4.
Possible Causes of Elevated ALP with Normal GGT
- Bone-related disorders, such as osteomalacia or Paget's disease, can cause elevated ALP with normal GGT 2, 4.
- Certain liver diseases, such as primary biliary cirrhosis, can also cause elevated ALP with normal GGT 4.
- Rheumatoid arthritis has been associated with elevated ALP and GGT, but the changes in these enzymes cannot be definitively related to drug therapy or hepatic involvement 4.
Diagnostic Approaches
- ALP isoenzyme analysis can help determine the source of elevated ALP, including bone, liver, or intestinal isoforms 3, 4.
- The combination of serum GGT and ALP has been shown to have better diagnostic performance in predicting asymptomatic choledocholithiasis secondary to cholecystolithiasis 5.
- Receiver operating characteristic (ROC) curve analysis can be used to determine the cutoff values, sensitivity, and specificity of GGT and ALP in diagnosing certain conditions 6, 5.