What are the causes of elevated Lactate Dehydrogenase (LDH) levels?

Causes of Elevated Lactate Dehydrogenase (LDH)

Elevated LDH levels are associated with numerous conditions involving cellular damage or increased cellular turnover, as LDH is released into the bloodstream whenever cells are damaged or destroyed.

Primary Categories of LDH Elevation

1. Tissue Damage and Cellular Injury

• Myocardial infarction/cardiac conditions 1
• Liver disease/disorders 1
• Muscle injury or disorders 1, 2
  • Strenuous exercise
  • Muscle trauma
  • Muscular dystrophies
• Hemolysis 1, 3
  • Hemolytic anemias
  • Blood sample hemolysis (false elevation)
• Ischemic events 1
  • Pulmonary embolism
  • Tissue infarction
  • Mechanical circulatory support device complications (e.g., pump thrombosis)

2. Malignancies

• Hematologic malignancies 1, 4
  • Lymphomas (markedly elevated LDH >900 IU/L)
  • Multiple myeloma
  • Leukemias
• Solid tumors with metastasis 1, 5
  • Particularly liver metastases
• Germ cell tumors 6, 1
  • Elevated in 40-60% of patients with seminoma
  • Used for prognostic stratification

3. Infections and Inflammatory Conditions

• Pneumonia 6
• Severe infections 1
• Sepsis 1

4. Specific Metabolic Disorders

• Glycogen storage diseases 6
  • Particularly GSD type I with elevated lactate levels

5. Other Conditions

• Renal conditions 1
• Secondary peritonitis 6
  • Ascitic LDH level higher than serum LDH level suggests secondary peritonitis

LDH Isoenzymes and Their Significance

LDH exists in five different isoenzymes that can help identify the source of elevation 1, 2:

Isoenzyme	Predominant Location	Associated Conditions When Elevated
LDH1 & LDH2	Heart, RBCs, kidneys	Myocardial infarction, hemolysis, renal infarction
LDH3	Lungs, lymphatic tissue	Pulmonary disease, lymphomas
LDH4	Placenta, kidneys	Pregnancy-related conditions
LDH5	Liver, skeletal muscle	Liver disease, muscle injury

Clinical Significance of LDH Elevation

Degree of Elevation

• Mild to moderate elevation: Common in many conditions
• Marked elevation (>900 IU/L): More suggestive of hematologic malignancies, metastatic disease, or severe infections 1
• Very high elevation (>10-fold normal): Associated with poor prognosis regardless of cause (mortality >50%) 7

Prognostic Value

• High LDH levels serve as a negative prognostic factor in multiple malignancies 1, 5
• In germ cell tumors, elevated LDH is used for risk stratification 6

Diagnostic Approach to Elevated LDH

When encountering elevated LDH, consider:

1. Clinical context - LDH lacks specificity and must be interpreted within the clinical picture 1
2. Comprehensive evaluation including:
   • Complete blood count with differential
   • Liver function tests
   • Renal function tests
   • Other specific markers based on clinical suspicion 1
3. Imaging studies as indicated by clinical findings:
   • Chest radiograph
   • Abdominal ultrasound
   • CT or MRI 1
4. Serial measurements are more valuable than single readings 1

Important Considerations

• LDH elevation alone should not drive treatment decisions due to its lack of specificity 1
• Sample processing can affect results - serum is preferred over plasma as platelet lysis in plasma can cause falsely elevated LDH 1
• LDH isoenzyme analysis may provide more specific information about the source of elevation 1, 2
• In patients with unexplained persistent LDH elevation, consider occult malignancy, particularly lymphoma 4

Remember that while elevated LDH is a sensitive marker for tissue damage, it lacks specificity and should be interpreted in conjunction with other clinical and laboratory findings.