What does an elevated Lactate Dehydrogenase (LDH) level indicate?

Elevated LDH: Clinical Significance and Diagnostic Implications

Elevated lactate dehydrogenase (LDH) indicates tissue damage or cell turnover and serves as an important but non-specific marker for various conditions including malignancies, hemolysis, tissue injury, and infections.

What is LDH?

LDH is an enzyme widely distributed in cells of various tissues that catalyzes the interconversion of lactate and pyruvate with NAD+/NADH coenzyme system 1. It is found in high concentrations in:

• Heart
• Liver
• Skeletal muscle
• Kidney
• Erythrocytes
• Lung (lesser amounts)
• Brain (lesser amounts)

Clinical Significance of Elevated LDH

Malignancies

• Hematologic malignancies: Particularly significant in lymphomas and leukemias 2
• Solid tumors: Marker for metastatic disease, especially liver metastases 3
• Germ cell tumors: Important prognostic factor 2
• Multiple myeloma: High LDH levels indicate aggressive "high-grade myeloma" with poor prognosis 4
• Melanoma: Elevated LDH is incorporated in AJCC staging for stage IV disease 2

Infections

• Elevated LDH is common in various infections (57% vs. 28% in patients without elevated LDH) 3

Tissue Damage/Destruction

• Myocardial infarction
• Hemolysis
• Muscle disease
• Pulmonary embolism
• Tumor lysis syndrome 2

Other Conditions

• Thrombotic thrombocytopenic purpura (TTP) 5
• Adult T-cell leukemia/lymphoma 2
• Plasma cell leukemia 2

Prognostic Value

Elevated LDH is associated with:

• Longer hospital stays (9.3 vs. 4.1 days) 3
• Higher in-hospital complication rates 3
• Higher mortality (26.6% vs. 4.3%) 3
• Independent predictor of mortality in admitted medical patients 3

LDH in Specific Conditions

Cancer

• Osteosarcoma: Elevated LDH correlates with worse prognosis and metastatic disease 2
• Germ cell tumors: Important for risk stratification and monitoring 2
• Lymphoma: Elevated LDH (>2× normal) is a key prognostic factor 2

Pleural Effusions

• Part of Light's criteria for distinguishing exudates from transudates:
  • Pleural fluid LDH divided by serum LDH > 0.6
  • Pleural fluid LDH > 2/3 the upper limits of normal for serum LDH 2

Tumor Lysis Syndrome

• Elevated LDH reflects high tumor burden and is a risk factor for developing tumor lysis syndrome 2

Limitations and Caveats

1. Non-specific marker: Elevated LDH alone has limited diagnostic specificity
2. Isoenzyme patterns: Different tissues release different LDH isoenzymes (LDH1-LDH5)
3. Laboratory interference: Radiographic contrast media can affect LDH measurements 6
4. Species differences: LDH patterns vary between species, important in veterinary medicine 1

Clinical Approach to Elevated LDH

When encountering elevated LDH:

1. Consider malignancy: Particularly if LDH is very high (≥800 IU/mL) 3
2. Evaluate for infection: Common cause of elevated LDH
3. Look for tissue damage: Myocardial, hepatic, muscle, or hemolysis
4. Consider isoenzyme testing: Can help identify the source tissue
5. Use as prognostic marker: Higher levels generally indicate worse outcomes

Key Takeaways

• Elevated LDH is a marker of cell damage or increased cell turnover
• Very high isolated LDH (≥800 IU/mL) warrants thorough investigation for cancer, especially metastatic disease
• LDH has important prognostic value in many conditions
• The pattern of LDH isoenzymes can help identify the affected tissue
• Always interpret LDH in clinical context as it is highly non-specific