What does it mean to have elevated Lactate Dehydrogenase (LDH) levels?

Elevated LDH: Clinical Significance and Evaluation

Elevated lactate dehydrogenase (LDH) levels indicate tissue damage or increased cellular turnover and warrant thorough investigation for underlying serious conditions including malignancy, infection, or tissue infarction. 1

Understanding LDH

LDH is an enzyme released into the bloodstream when cells are damaged or destroyed. It is present in nearly all body tissues, with different isoenzymes predominating in different organs:

• LDH1 & LDH2: Heart, red blood cells, kidneys
• LDH3: Lungs, lymphatic tissue
• LDH4: Placenta, kidneys
• LDH5: Liver, skeletal muscle

Common Causes of Elevated LDH

Malignancies

• Solid tumors with metastasis (particularly liver metastases)
• Hematologic malignancies (lymphomas, multiple myeloma)
• Advanced germ cell tumors (elevated LDH is used for prognostic stratification in testicular cancer) 2
• Melanoma (elevated LDH is associated with worse survival in stage IV disease) 2

Tissue Damage

• Myocardial infarction
• Pulmonary embolism
• Tissue infarction
• Muscle injury

Infections

• Severe infections (including pneumonia, sepsis)
• Disseminated histoplasmosis in immunocompromised patients 3

Other Conditions

• Hemolysis
• Liver disease
• Glycogen storage diseases 1

Prognostic Significance

The degree of LDH elevation often correlates with disease severity:

• Moderately elevated LDH (2-3× normal): Various conditions, less specific
• Highly elevated LDH (>3× normal): Associated with more severe disease
• Very high LDH (≥10× normal): Associated with poor prognosis regardless of cause, with mortality >50% 1, 4

Clinical Evaluation of Elevated LDH

Initial Workup

1. Complete blood count with differential

   • To evaluate for anemia, hemolysis, or hematologic malignancies

2. Comprehensive metabolic panel

   • Liver function tests to distinguish isolated LDH elevation from broader hepatic dysfunction
   • Renal function tests

3. Additional laboratory tests based on clinical suspicion:

   • Tumor markers (AFP, β-HCG) if germ cell tumor suspected 2
   • Blood cultures if infection suspected

Imaging Studies

• Chest radiograph - For pulmonary pathology
• Abdominal ultrasound or CT - For liver metastases, lymphadenopathy
• PET-CT - Consider for suspected malignancy, particularly if other tests are negative

Special Considerations

• Isolated very high LDH (≥800 IU/L without liver enzyme elevation) strongly suggests malignancy and warrants thorough investigation 5
• Persistent unexplained LDH elevation may be an early marker of occult malignant lymphoma 6
• Serial measurements are more valuable than single readings when monitoring disease progression or treatment response

Important Caveats

1. LDH lacks specificity - Must be interpreted in clinical context
2. False elevations can occur with hemolyzed specimens
3. Serum is preferred over plasma for LDH testing to avoid falsely elevated results due to platelet lysis
4. Treatment should never be based solely on elevated LDH - Further diagnostic workup is always required

Monitoring

• In patients with known malignancy, serial LDH measurements can help monitor treatment response
• Rising LDH levels may indicate disease progression or treatment failure
• Normalization of previously elevated LDH may indicate effective treatment

In summary, elevated LDH requires thorough evaluation to identify the underlying cause, with particular attention to potential malignancies, infections, and tissue damage. The degree of elevation can provide prognostic information, with very high levels associated with poorer outcomes.