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

Causes of Elevated Lactate Dehydrogenase (LDH) Levels

Elevated LDH levels can indicate tissue damage or disease across multiple organ systems, with malignancies, hemolysis, and tissue ischemia being the most significant causes requiring thorough investigation.

Common Causes of Elevated LDH

LDH is an enzyme found in nearly all cells of the body, with high concentrations in the heart, liver, muscles, kidneys, lungs, and blood cells 1. When these tissues are damaged, LDH is released into the bloodstream, causing elevated serum levels. Normal values in adults typically range from 125-220 U/L (or IU/L).

Malignancies

• Hematologic malignancies: Markedly elevated levels (>900 IU/L) 1

  • Malignant lymphoma (can be an early marker of occult disease) 2
  • Multiple myeloma and plasma cell leukemia 3
  • Leukemias

• Solid tumors: Moderately elevated levels 1

  • Testicular cancer (particularly seminomas and non-seminomas) 3
  • Metastatic disease (common in advanced stages)
  • Ovarian cancer
  • Lung cancer

Tissue Damage/Ischemia

• Cardiac conditions

  • Myocardial infarction
  • Heart failure
  • Cardiomyopathy

• Liver disorders

  • Hepatitis
  • Cirrhosis
  • Liver congestion

• Muscle disorders

  • Muscular dystrophy
  • Rhabdomyolysis
  • Trauma
  • Strenuous exercise

Hemolytic Conditions

• Hemolytic anemias
• Thrombotic thrombocytopenic purpura (TTP) 4
• Intravascular hemolysis

Infectious/Inflammatory Conditions

• Pneumonia
• Sepsis
• Meningitis
• Encephalitis

Other Conditions

• Preeclampsia 1
• Renal disease/failure
• Pulmonary embolism
• Pancreatitis
• Intestinal ischemia

LDH Isoenzymes and Their Significance

LDH exists as five isoenzymes (LDH1-LDH5), each predominant in different tissues:

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 Approach to Elevated LDH

Initial Evaluation

When encountering elevated LDH levels, a comprehensive evaluation should include:

• Complete blood count with differential
• Liver function tests
• Renal function tests
• Inflammatory markers (CRP, ESR)
• Cardiac markers if cardiac involvement is suspected 1

Imaging Studies

Based on clinical suspicion:

• Chest radiograph
• Abdominal ultrasound
• Echocardiography (if cardiac symptoms present)
• CT or MRI based on diagnostic suspicion 1

Special Considerations

Malignancy

• Elevated LDH is associated with poor prognosis in many cancers 5
• In plasma cell leukemia, elevated LDH reflects high tumor burden 3
• In testicular cancer, LDH is a mandatory tumor marker along with AFP and β-HCG 3

Peritoneal Fluid Analysis

• In ascites, LDH can help differentiate between causes:
  • Secondary peritonitis is suggested by ascitic fluid LDH higher than serum LDH 3
  • In tuberculous peritonitis, LDH may be elevated alongside other markers 3

Pregnancy

• LDH can be elevated in preeclampsia 3
• Normal pregnancy may cause mild LDH elevation
• CA-125 can be elevated in pregnancy, but LDH typically remains within normal limits unless there's a complication 3

Monitoring and Prognostic Value

• Serial LDH measurements provide greater value than single determinations 1
• Normalization during treatment suggests therapeutic response
• Persistent elevation or rising levels may indicate disease progression or treatment failure 1

Remember that LDH has low specificity and should always be interpreted in the context of clinical presentation and other laboratory findings. An elevated LDH without obvious cause warrants thorough investigation, as it may be an early marker of occult malignancy 2.