What tests diagnose heavy metal exposure in the body?

Tests for Measuring Heavy Metals in the Body

The most effective tests for measuring heavy metals in the body include 24-hour urine collection, blood tests, and liver biopsy for specific metals like copper, with the choice of test depending on the specific metal and clinical scenario. 1

Primary Testing Methods

Blood Tests

• Direct measurement of circulating heavy metals
• Best for: Recent acute exposure assessment
• Specific metals commonly tested:
  • Lead (highest positivity rate in occupational monitoring at 26.2%) 2
  • Mercury
  • Arsenic
  • Cadmium

Urine Tests

• 24-hour urine collection is the gold standard for many metals
• Types of urine testing:
  • Baseline/unprovoked - reflects current exposure from bloodstream 3, 4
  • Post-challenge/provoked - after administration of chelating agent (e.g., D-penicillamine) to assess total body burden 3, 4
• Highest positivity rate: Zinc testing (28.1%) 2
• Specific recommendations:
  • Copper: Values >100 μg/24 hours (1.6 μmol/24 hours) are typically diagnostic for Wilson's disease 1
  • For children, D-penicillamine challenge test with values >1600 μg copper/24 hours indicates Wilson's disease 1

Tissue Biopsy

• Liver biopsy - gold standard for copper measurement
  • Diagnostic threshold: ≥250 μg/g dry weight for Wilson's disease 1
  • Some research suggests ≥70 μg/g dry weight may increase sensitivity 1
• Sample handling: Use disposable needles and copper-free containers 1

Metal-Specific Testing Approaches

Copper

• Primary tests:
  1. Serum ceruloplasmin (<200 mg/L or 20 mg/dL suggests deficiency) 1
  2. 24-hour urinary copper excretion (>40 μg/24h warrants investigation) 1
  3. Serum copper (may be decreased proportionally to ceruloplasmin) 1
  4. Non-ceruloplasmin-bound copper calculation 1
  5. Liver biopsy for quantitative copper determination 1

Vitamin B12 (Cobalamin)

• Recommended combination of at least two biomarkers:
  • Holo-transcobalamin (holo-TC)
  • Methylmalonic acid (MMA)
  • Serum cobalamin (as replacement for holo-TC when unavailable) 1

Multiple Metal Screening

• Expanded panel testing is recommended as it can identify additional exposures missed by single-element testing
  • Studies show 42% of blood and 48% of urine specimens negative for initially tested metals had at least one elevated result when tested with expanded panels 2

Clinical Considerations

When to Test

• Indications for testing:
  • Unexplained neurological symptoms
  • Liver abnormalities of uncertain cause in individuals 3-45 years 1
  • Suspected occupational exposure
  • Environmental exposure concerns
  • Specific symptoms associated with known metal toxicity 5

Sample Collection and Handling

• For urine:

  • Complete 24-hour collection (verify with creatinine measurement)
  • Avoid copper contamination of collection apparatus 1
  • Temperature storage of 2-8°C for up to 7 days 1

• For blood:

  • Collect before blood transfusion or IM administration of supplements 1
  • Store at -20°C for up to 30 days or colder for longer storage 1

Common Pitfalls

• Single element testing may miss significant exposures to other metals 2
• Urine spot samples have too much variability for reliable heavy metal assessment 1
• Interpreting 24-hour urinary copper excretion can be difficult due to overlap with findings in other liver diseases 1
• Non-ceruloplasmin-bound copper calculations depend on the accuracy of both serum copper and ceruloplasmin measurements 1
• In later stages of Wilson's disease, copper distribution in the liver may be inhomogeneous, affecting biopsy results 1

By combining appropriate testing methods based on clinical presentation and suspected exposure, clinicians can effectively assess heavy metal burden and guide appropriate treatment decisions.