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Difficulty: MediumOrdering Laboratory Tests

A 52-year-old man presents to the primary care clinic for a routine health maintenance examination. He has no acute complaints and specifically denies fatigue, abdominal pain, nausea, vomiting, or changes in bowel habits. He also denies any joint or bone pain. His past medical history is significant for well-controlled essential hypertension and hyperlipidemia, for which he takes lisinopril and atorvastatin. He consumes 1 to 2 glasses of wine per week and does not use tobacco or illicit drugs. Family history is unremarkable. Vital signs are within normal limits. Physical examination reveals a non-distended, non-tender abdomen with no hepatosplenomegaly. Skin examination shows no jaundice or stigmata of chronic liver disease.

Comprehensive metabolic panel results are as follows:

Laboratory TestResultReference Range
Sodium140 mEq/L136-145 mEq/L
Potassium4.2 mEq/L3.5-5.0 mEq/L
Creatinine0.9 mg/dL0.7-1.3 mg/dL
Calcium9.4 mg/dL8.4-10.2 mg/dL
Total protein7.0 g/dL6.0-7.8 g/dL
Albumin4.2 g/dL3.5-5.5 g/dL
Total bilirubin0.8 mg/dL0.1-1.2 mg/dL
Aspartate aminotransferase (AST)28 U/L10-40 U/L
Alanine aminotransferase (ALT)32 U/L10-40 U/L
Alkaline phosphatase (ALP)285 U/L40-120 U/L

Which of the following is the most appropriate next step in diagnostic evaluation?

  1. A
    Measurement of serum 25-hydroxyvitamin D
  2. B
    Antimitochondrial antibody titer
  3. Measurement of serum gamma-glutamyl transferaseAnswer
  4. D
    Right upper quadrant abdominal ultrasound
  5. E
    Hepatitis B and C serologies

Answer

The most appropriate next step is the measurement of serum gamma-glutamyl transferase (GGT).
The correct answer is the measurement of serum gamma-glutamyl transferase (GGT). This patient presents with an asymptomatic, isolated elevation of alkaline phosphatase (ALP). The other liver chemistry values (aspartate aminotransferase, alanine aminotransferase, and total bilirubin) are completely normal. ALP is an enzyme found in several tissues throughout the body, most notably the liver, bone, placenta, and intestines. When an isolated elevation is discovered, the most appropriate first step is to determine its tissue of origin. This is accomplished by measuring another enzyme typically elevated in hepatobiliary disease, such as GGT or 5'-nucleotidase. GGT is highly sensitive for biliary disease but is not found in bone. Therefore, an elevated GGT confirms a hepatic origin of the ALP, prompting further hepatobiliary evaluation (such as a right upper quadrant ultrasound). Conversely, a normal GGT suggests a bone origin (e.g., Paget disease, osteomalacia), which would prompt bone-specific evaluation.

Step-by-Step Solution

1
Analyze the laboratory panel to identify the primary abnormality.
The patient has an isolated, asymptomatic elevation of alkaline phosphatase (ALP) with strictly normal aminotransferases (AST, ALT) and total bilirubin.
Identifying the specific pattern of liver enzyme elevation determines the diagnostic algorithm.
2
Formulate a differential diagnosis for isolated ALP elevation.
Elevated ALP can originate from multiple sources, primarily the liver (suggesting cholestatic injury) or bone (suggesting increased osteoblast activity).
Because the source of the enzyme is not specific to one organ system, identifying the tissue origin is required before evaluating for specific diseases.
3
Select the most appropriate initial diagnostic test to differentiate the source.
Measurement of serum gamma-glutamyl transferase (GGT) or 5'-nucleotidase is indicated.
GGT is present in hepatocytes and biliary epithelia but absent in bone. An elevated GGT confirms a hepatic origin, whereas a normal GGT confirms a bone origin.

Key Concept

The initial step in evaluating an isolated elevated alkaline phosphatase (ALP) in an asymptomatic patient is to determine its tissue of origin by measuring serum gamma-glutamyl transferase (GGT) or 5'-nucleotidase.
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Ordering Laboratory Tests

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