What labs to order in a 21-year-old male with isolated elevated Alkaline Phosphatase (ALP) and normal liver enzymes, including Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Gamma-Glutamyl Transferase (GGT), normal Parathyroid Hormone (PTH), and normal calcium levels?

Diagnostic Approach to Isolated Elevated ALP in a Young Adult Male

For a 21-year-old male with isolated elevated alkaline phosphatase (ALP) and normal ALT/AST/GGT, PTH, and calcium levels, you should order a bone-specific ALP isoenzyme test, vitamin D level, and abdominal ultrasound to determine the source of the elevation. 1

Initial Diagnostic Considerations

When evaluating isolated ALP elevation with normal liver enzymes, it's crucial to determine whether the ALP is of hepatic or non-hepatic origin. Since GGT is normal in this case, a hepatic source is less likely, and bone origin should be strongly considered.

First-line Laboratory Tests to Order:

• Bone-specific ALP isoenzyme test - This will help determine if the elevated ALP is of bone origin
• 25-hydroxyvitamin D level - To assess for vitamin D deficiency which can affect bone metabolism
• Phosphate level - Important to evaluate for conditions like X-linked hypophosphatemia 1
• 5'-nucleotidase - Can help differentiate between hepatic and non-hepatic sources of ALP elevation
• Liver isoenzyme of ALP - To confirm if any component is from liver

Imaging Studies:

• Abdominal ultrasound - First-line imaging to evaluate for any subtle hepatobiliary abnormalities 1
• Bone scan - Consider if bone-specific ALP is elevated or if other bone markers are abnormal

Diagnostic Algorithm

1. Confirm ALP elevation with repeat testing

2. Determine ALP source with isoenzyme testing

   • If bone-specific ALP is elevated → Evaluate for bone disorders
   • If liver-specific ALP is elevated despite normal GGT → Consider infiltrative liver diseases

3. Based on isoenzyme results:

   • Bone origin: Consider Paget's disease, osteomalacia, bone growth (normal in young adults), fracture healing
   • Liver origin: Consider infiltrative liver diseases (e.g., sarcoidosis, amyloidosis), early primary biliary cholangitis, medication effect

Key Considerations and Pitfalls

• Don't assume normal GGT completely rules out liver disease - Some infiltrative liver conditions can present with isolated ALP elevation 1, 2
• Consider age-appropriate causes - In a 21-year-old male, bone growth can cause physiologic ALP elevation
• Beware of transient hyperphosphatasemia - Though more common in children under 5, it can cause dramatic ALP elevations without pathology 3
• Don't miss malignancy - While less common in young adults, isolated elevated ALP can be associated with malignancy (57% in one study, though typically in older populations) 4

Uncommon but Important Considerations

• Medication review is essential - Some medications can cause isolated ALP elevation
• Consider rare genetic conditions - Such as benign familial hyperphosphatasemia
• Rule out early non-alcoholic fatty liver disease (NAFLD) - Though typically presents with transaminase elevations, a subset of patients can present with isolated ALP elevation 2

If initial workup is inconclusive, consider referral to a specialist for further evaluation, as isolated ALP elevation can sometimes indicate serious underlying conditions that require prompt diagnosis and management.