What causes elevated lactate dehydrogenase (LDH) levels?

Causes of Elevated Lactate Dehydrogenase (LDH) Levels

Elevated LDH levels are primarily caused by malignancies (particularly hematologic cancers and metastatic disease), infections, tissue damage, and organ dysfunction, with the degree of elevation often correlating with disease severity and mortality risk. 1

Major Causes of Elevated LDH

Malignancies

• Hematologic malignancies

  • Multiple myeloma and plasma cell leukemia 2, 1
  • Malignant lymphomas 3, 4
  • High LDH in myeloma indicates "high-grade myeloma" with aggressive course 4

• Solid tumors

  • Metastatic cancer, especially liver metastases 1, 5
  • Small-cell lung cancer
  • Hepatocellular carcinoma
  • Bone tumors (Ewing sarcoma, osteogenic sarcoma) 1

Cardiovascular Conditions

• Myocardial infarction
• Heart failure
• Mechanical circulatory support device complications
  • Pump thrombosis (LDH elevation can occur up to 3 months before clinically significant thrombosis) 2
  • Hemolysis in patients with ventricular assist devices 2

Infections

• Severe infections and sepsis 1, 5
• Tuberculosis (including tuberculous peritonitis) 1

Liver Disorders

• Hepatitis (viral, alcoholic, or drug-induced)
• Cirrhosis
• Liver congestion (from heart failure) 1

Hematologic Disorders

• Hemolytic anemias
• Thrombotic thrombocytopenic purpura
• Disseminated intravascular coagulation 1

Other Causes

• Muscle disorders and trauma
• Strenuous exercise
• Renal disease
• Pulmonary embolism
• Bowel perforation (secondary peritonitis) 1

Clinical Significance of LDH Elevation

Diagnostic Value

• Very high isolated LDH (≥800 IU/ml) is a distinguishing biomarker for:
  • Cancer (27% vs 4% in controls)
  • Liver metastases (14% vs 3%)
  • Hematologic malignancies (5% vs 0%)
  • Infections (57% vs 28%) 5

Prognostic Value

• LDH elevation >10 times normal is associated with:
  • ICU admission in 73% of cases
  • Mortality rate of 53% 6
• In hospitalized patients, very high isolated LDH predicts:
  • Longer hospital stays (9.3 vs 4.1 days)
  • Higher in-hospital complications
  • Higher mortality (26.6% vs 4.3%) 5

Disease Monitoring

• In malignancies, LDH levels can serve as a marker of:
  • Treatment response (normalization with effective treatment)
  • Disease progression (elevation with therapeutic failure) 6, 7
• In patients with mechanical circulatory support, LDH elevation above 2.5 times the upper limit of normal requires evaluation for pump thrombosis 2

Diagnostic Approach for Elevated LDH

1. Assess degree of elevation:

   • Mild-moderate elevation: Consider broader differential
   • Very high elevation (>10x normal): Higher mortality risk regardless of cause 6

2. Look for associated symptoms and laboratory abnormalities:

   • Fever, weight loss → infection or malignancy
   • Chest pain → cardiac cause
   • Abdominal symptoms → liver disease
   • Anemia, thrombocytopenia → hematologic disorders

3. Consider imaging based on clinical suspicion:

   • CT scan for suspected malignancy
   • Echocardiography for cardiac causes
   • Ultrasound for liver disorders

4. Further specialized testing:

   • Bone marrow examination for suspected hematologic malignancies
   • Specific tumor markers for suspected malignancies
   • LDH isoenzyme analysis may help narrow differential diagnosis

Important Clinical Pearls

• LDH alone cannot differentiate between benign and malignant causes, regardless of the degree of elevation 6
• In patients with no apparent cause for elevated LDH, thorough investigation including abdominal CT scan is warranted 3
• In patients with mechanical circulatory support devices, LDH is a key marker for device complications 2
• Serial LDH measurements are valuable for monitoring disease progression and treatment response in malignancies 7