What is the appropriate workup for an 18-year-old male with fatigue and mildly elevated bilirubin (hyperbilirubinemia)?

Diagnostic Workup for Mildly Elevated Bilirubin (1.7) in an 18-Year-Old Male with Fatigue

The appropriate initial workup for an 18-year-old male with fatigue and mildly elevated bilirubin of 1.7 mg/dL should include fractionated bilirubin levels, complete blood count with peripheral smear, liver function tests, and abdominal ultrasound to determine the cause and guide management. 1

Initial Laboratory Evaluation

1. Fractionated bilirubin levels to determine if hyperbilirubinemia is predominantly:

   • Unconjugated (<20-30% conjugated bilirubin) - suggesting Gilbert's syndrome, hemolysis
   • Conjugated (>35% conjugated bilirubin) - suggesting hepatocellular or biliary tract disease

2. Complete blood count with differential and peripheral smear

   • Essential to evaluate for hemolytic causes (e.g., hereditary spherocytosis) 2
   • Look for anemia, abnormal red cell morphology, and reticulocyte count

3. Liver function tests

   • ALT, AST (hepatocellular damage)
   • Alkaline phosphatase, γ-glutamyltransferase (biliary obstruction)
   • Albumin, total protein, prothrombin time/INR (synthetic function)

Imaging

• Abdominal ultrasound is the first-line imaging technique (sensitivity 32-100%, specificity 71-97%) 1
  • Evaluates for biliary obstruction, hepatomegaly, splenomegaly
  • Particularly important if conjugated hyperbilirubinemia is present

Focused Diagnostic Considerations for This Case

Given the patient's age (18) and mild elevation (1.7 mg/dL), particular attention should be paid to:

1. Gilbert's syndrome - most likely cause in a young male with predominantly unconjugated hyperbilirubinemia

   • Often presents with mild jaundice and fatigue
   • Usually exacerbated by fasting, illness, or physical exertion

2. Hemolytic disorders - consider hereditary spherocytosis or other hemolytic anemias

   • Peripheral smear and reticulocyte count are crucial 2

3. Viral hepatitis - consider serologic testing for hepatitis viruses

   • Particularly if transaminases are elevated
   • EBV infection can cause hyperbilirubinemia with fatigue 3

4. Medication review - identify any medications that could cause hyperbilirubinemia 1

Follow-up Testing Based on Initial Results

• If predominantly unconjugated hyperbilirubinemia with normal other tests:

  • Consider genetic testing for Gilbert's syndrome (UGT1A1 mutation) 1
  • Provocation test (24-hour fast) may be considered

• If predominantly conjugated hyperbilirubinemia or abnormal ultrasound:

  • Consider MRI with MRCP for further evaluation 1
  • Evaluate for Dubin-Johnson or Rotor syndrome if familial 4

• If evidence of hemolysis:

  • Hemolysis workup (direct Coombs test, haptoglobin, LDH)
  • Consider hereditary spherocytosis evaluation 2

Monitoring and Follow-up

• For mild elevations (<2× ULN) with no other abnormalities:
  • Repeat testing in 2-4 weeks
  • If persistent, proceed with more comprehensive diagnostic workup 1

Common Pitfalls to Avoid

1. Overlooking Gilbert's syndrome - most common cause of mild unconjugated hyperbilirubinemia in young adults

2. Missing hemolytic disorders - can coexist with other conditions and significantly worsen hyperbilirubinemia 2

3. Assuming normal aminotransferases rule out significant liver disease - this is incorrect 1

4. Neglecting medication review - certain medications can cause isolated hyperbilirubinemia without ALT elevations 1

5. Overinvestigation of mild, isolated unconjugated hyperbilirubinemia - may lead to unnecessary testing and patient anxiety