What is Lactate Dehydrogenase (LDH)?

Lactate Dehydrogenase (LDH): Clinical Significance and Diagnostic Utility

Lactate dehydrogenase (LDH) is an intracellular enzyme that catalyzes the reversible conversion of pyruvate to lactate in the final step of anaerobic glycolysis, and serves as an important clinical biomarker for tissue damage across multiple organ systems. 1, 2

Biochemical Properties and Function

• Enzyme Classification: LDH is an oxidoreductase that catalyzes the interconversion between pyruvate and lactate using NAD+/NADH as a coenzyme system
• Structure: Composed of five isoenzymes (LDH1-LDH5) formed from different combinations of two subunits (M and H)
• Distribution:
  • Widely distributed throughout the body
  • High concentrations in heart, liver, skeletal muscle, kidney, and erythrocytes
  • Lower concentrations in lung, smooth muscle, and brain
  • Each tissue has a characteristic isoenzyme pattern

Clinical Significance

As a Biomarker of Cell Death and Tissue Damage

LDH is primarily used as a marker of cell death because:

• It is released into the bloodstream when cell membranes are damaged 1
• Normal cells contain LDH in the cytoplasm, and its presence in serum indicates cell lysis
• The enzyme is stable in body fluids, making it a reliable marker of tissue damage

Specific Clinical Applications

1. Cancer Monitoring and Prognosis:

   • Elevated LDH is an independent predictor of poor outcome in stage IV melanoma 1
   • Used in monitoring testicular germ cell tumors, particularly nonseminomas 1
   • Serves as a prognostic marker in various malignancies due to the Warburg effect (increased glycolysis in cancer cells) 3

2. Pleural Effusion Classification:

   • Part of Light's criteria to differentiate exudative from transudative effusions:
     • Pleural fluid is an exudate if pleural fluid LDH divided by serum LDH > 0.6
     • Pleural fluid LDH > 2/3 the upper limit of normal for serum LDH 1

3. Inflammatory Conditions:

   • Elevated in severe COVID-19 and other inflammatory diseases
   • Associated with higher mortality in ARDS and severe inflammatory conditions 4

4. Other Clinical Scenarios:

   • Myocardial infarction (cardiac damage)
   • Hemolysis (red blood cell destruction)
   • Liver disease
   • Muscle damage/rhabdomyolysis

Diagnostic Considerations

Interpretation of Results

• Reference Range: Laboratory-specific; typically measured in U/L
• Timing: Elevations may persist for days after tissue injury due to LDH's relatively long half-life
• Isoenzyme Analysis: Can help identify the source of tissue damage based on the specific isoenzyme pattern 5

Limitations and Pitfalls

1. Low Specificity:

   • Elevated in numerous conditions involving cell damage
   • Cannot be used alone to diagnose specific diseases

2. False Positives:

   • Hemolyzed blood samples can cause falsely elevated results
   • Multiple non-pathological conditions can increase LDH levels

3. Sample Handling:

   • Proper collection and handling is essential as hemolysis artificially elevates LDH

Special Considerations in Specific Diseases

Germ Cell Tumors

• LDH is one of three essential tumor markers (along with AFP and β-HCG) 1
• Particularly useful in advanced disease staging
• Elevated in approximately 40-60% of patients with seminoma 1

Pleural Disease

• Critical component of Light's criteria for pleural effusion classification
• Used in diagnostic algorithms for pleural infection 1

Melanoma

• Elevated LDH is incorporated into the AJCC staging system as an independent predictor of poor outcome in stage IV disease 1

In summary, while LDH is a non-specific marker of tissue damage, its measurement provides valuable clinical information when interpreted in the appropriate clinical context and alongside other diagnostic tests. Its utility spans multiple medical specialties, from oncology to pulmonology and cardiology.