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

Causes of Elevated Lactate Dehydrogenase (LDH)

Elevated LDH levels can indicate a wide range of pathological conditions involving cell damage or increased cell turnover, with malignancies, infections, and tissue damage being the most significant causes requiring prompt clinical attention.

Common Causes of Elevated LDH

Malignancies

• Hematologic malignancies:

  • Lymphomas (both Hodgkin's and non-Hodgkin's) 1
  • Acute lymphoblastic leukemia (ALL) - particularly high elevations (>900 IU/L) 2
  • Acute non-lymphoblastic leukemia (ANLL) 2
  • Multiple myeloma and plasma cell leukemia 3

• Solid tumors:

  • Metastatic cancer, especially liver metastases 4
  • Small-cell lung cancer 3
  • Hepatocellular carcinoma 3
  • Ewing sarcoma and osteogenic sarcoma 3

Tissue Damage and Necrosis

• Cardiac conditions:

  • Myocardial infarction 3
  • Heart failure 3

• Liver disorders:

  • Hepatitis (viral, alcoholic, or drug-induced) 3
  • Cirrhosis 3
  • Liver congestion (from heart failure) 3

• Muscle disorders:

  • Rhabdomyolysis
  • Muscular dystrophy
  • Strenuous exercise 3

• Renal conditions:

  • Renal infarction - characterized by strikingly elevated LDH with minimal increases in other liver enzymes 5
  • Kidney disease 3

Infections

• Pneumonia 3
• Severe infections and sepsis 4
• Tuberculosis (including tuberculous peritonitis) 3

Other Causes

• Hemolysis (including hemolytic anemia and in vitro hemolysis of blood samples) 3
• Intestinal and mesenteric ischemia
• Pulmonary embolism
• Pancreatitis
• Bowel perforation (secondary peritonitis) 3

Diagnostic Significance

LDH is a nonspecific marker that requires careful interpretation:

1. Very high isolated LDH (≥800 IU/L without concomitant elevations of ALT and AST) should prompt investigation for:

   • Metastatic cancer (14% of cases)
   • Hematologic malignancies (5% of cases)
   • Severe infections (57% of cases) 4

2. Markedly elevated LDH in acute leukemia is highly suggestive of ALL rather than ANLL 2

3. LDH in lymphoma serves as a prognostic indicator - normal values are associated with better response to therapy and longer survival 1

4. Secondary peritonitis may show elevated LDH in ascitic fluid, with ascitic LDH levels higher than serum LDH levels 3

Clinical Implications

• Very high isolated LDH is associated with:

  • Longer hospital stays (9.3 vs 4.1 days)
  • Higher in-hospital complication rates
  • Higher mortality rates (26.6% vs 4.3%) 4

• LDH elevation is an independent predictor of mortality in hospitalized medical patients 4

Practical Approach to Elevated LDH

1. Consider the degree of elevation:

   • Mild to moderate elevation: More likely due to less severe conditions
   • Marked elevation (>500 IU/L): Consider malignancy, especially if >900 IU/L in the context of hematologic disorders

2. Evaluate for sample hemolysis which can falsely elevate LDH

3. Look for associated symptoms and laboratory abnormalities:

   • Fever, weight loss, night sweats: Consider malignancy or infection
   • Chest pain: Consider cardiac causes
   • Abdominal pain: Consider hepatic, pancreatic, or intestinal causes
   • Elevated bilirubin/alkaline phosphatase: Consider liver disease
   • Elevated creatinine: Consider renal causes

4. Consider appropriate imaging based on clinical suspicion:

   • Ultrasound for liver disease
   • CT for suspected malignancy or infection
   • Specific testing for suspected hematologic malignancies

Remember that LDH is highly nonspecific, and its elevation should be interpreted in the clinical context of the patient's presentation and other laboratory findings.