What does an elevated lactate dehydrogenase (LDH) level indicate?

Elevated Lactate Dehydrogenase (LDH): Clinical Significance and Implications

Elevated lactate dehydrogenase (LDH) levels indicate tissue damage or cell death and serve as a non-specific marker for various serious conditions including cancer, infection, hemolysis, myocardial infarction, and organ dysfunction.

What is LDH?

• LDH is an oxidoreductase enzyme that catalyzes the reversible conversion between pyruvate and lactate with NAD+/NADH as a coenzyme system 1
• It is widely distributed in the body with high concentrations found in the heart, liver, skeletal muscle, kidney, and erythrocytes 2
• LDH is primarily located in the cytoplasm of cells but can also be found in multiple organelles 1

Clinical Significance of Elevated LDH

Cancer

• Elevated LDH is a distinguishing biomarker for the presence of cancer (27% vs 4% in patients with normal LDH) 3
• Particularly associated with liver metastases (14% vs 3%) and hematologic malignancies (5% vs 0%) 3
• In germ cell tumors, LDH elevation is seen in 40-60% of patients with advanced disease 4
• LDH is a mandatory marker for staging and prognostication in advanced germ cell tumors 4

Infection and Inflammation

• Significantly associated with infections (57% vs 28% compared to controls) 3
• Serves as a marker of severity in inflammatory conditions 5
• High LDH levels in COVID-19 patients correlate with increased mortality risk 5

Pleural Effusions

• LDH is a key component of Light's criteria for distinguishing exudative from transudative pleural effusions 4
• Pleural fluid is considered exudative if:
  • Pleural fluid protein/serum protein ratio > 0.5
  • Pleural fluid LDH/serum LDH ratio > 0.6
  • Pleural fluid LDH > 2/3 the upper limit of normal for serum LDH 4

Other Conditions

• Elevated in various organ disorders including myocardial infarction, liver disease, muscle disease, and hemolysis 4
• Can be elevated in Pompe disease along with other markers like creatine kinase (CK) 4
• Sample hemolysis can falsely elevate LDH levels 4

Prognostic Value

• Very high isolated LDH (≥800 IU/ml) is associated with:
  • Longer hospital stays (9.3 vs 4.1 days) 3
  • Significantly more in-hospital complications 3
  • Higher mortality rate (26.6% vs 4.3%) 3
• Independent predictor of mortality in hospitalized medical patients 3
• Used for risk stratification in certain cancers, particularly germ cell tumors 4

Limitations of LDH as a Diagnostic Marker

• Highly non-specific due to its widespread distribution in body tissues 2
• Elevation can occur in numerous disorders, limiting its diagnostic specificity 4
• More clinically useful when:
  • Separated into isoenzyme fractions 2
  • Interpreted in context with other clinical and laboratory findings 4
  • Monitored over time to assess disease progression or treatment response 5

Clinical Approach to Elevated LDH

1. Consider the degree of elevation

   • Very high isolated elevations (≥800 IU/ml) warrant thorough investigation for malignancy and severe infection 3

2. Look for associated symptoms and laboratory abnormalities

   • Evaluate for signs of tissue damage in major organs (heart, liver, muscle, kidney) 2
   • Check for other markers of cell injury specific to suspected organs 1

3. Consider common causes based on clinical context

   • In patients with pleural effusions, use LDH as part of Light's criteria 4
   • In patients with suspected germ cell tumors, measure LDH along with AFP and β-HCG 4
   • In patients with lymphoma, LDH is an important prognostic marker 4

4. Monitor trends

   • Serial measurements are more informative than single values 5
   • Rising levels may indicate disease progression or treatment failure 1

Common Pitfalls

• Interpreting isolated LDH elevation without clinical context can lead to unnecessary testing 4
• Sample hemolysis can cause falsely elevated results 4
• Failure to consider the wide range of conditions that can elevate LDH 2
• Not recognizing that very high LDH levels, even when isolated, warrant thorough investigation due to association with serious underlying conditions and mortality 3