What does an elevated Lactate Dehydrogenase (LDH) level in a blood test indicate?

Lactate Dehydrogenase (LDH) Blood Test: Clinical Significance and Interpretation

Elevated LDH levels in blood tests indicate tissue damage or cellular destruction across multiple organ systems and are associated with various pathological conditions including cancer, myocardial infarction, hemolysis, and infection.

What is LDH?

• Lactate dehydrogenase (LDH) is an enzyme widely distributed in cells of various tissues that catalyzes the interconversion of lactate and pyruvate with NAD+/NADH coenzyme system 1
• High concentrations of LDH are found in the heart, liver, skeletal muscle, kidney, and erythrocytes, with lesser amounts in lung, smooth muscle, and brain 1

Normal vs. Elevated LDH Levels

• Normal LDH levels vary by laboratory but typically range between 125-225 IU/L 2
• Elevated LDH levels (>1.5 times the upper limit of normal) indicate tissue damage or increased cellular turnover 3
• Very high isolated LDH levels (≥800 IU/L) without concomitant liver enzyme elevations warrant thorough investigation for severe underlying disease 4

Clinical Significance of Elevated LDH

Cancer Markers

• Elevated LDH is a tumor marker in multiple malignancies:
  • Testicular germ cell tumors: LDH is one of three critical serum markers (along with AFP and β-HCG) for diagnosis, prognosis, and treatment monitoring 3
  • Osteosarcoma: Elevated serum LDH is associated with worse prognosis and correlates with metastatic disease 3
  • Lymphoma: Markedly elevated LDH (>500 IU/L) is associated with high-grade lymphoma and poorer outcomes 5, 2
  • Multiple myeloma: High LDH levels indicate a more aggressive "high-grade myeloma" with extraosseous features 5
  • Acute lymphoblastic leukemia (ALL): Significantly higher LDH levels (often >900 IU/L) compared to acute non-lymphoblastic leukemia 6
  • Plasma cell leukemia: Elevated LDH reflects high tumor burden and aggressive clinical presentation 3
  • Melanoma: Elevated LDH is incorporated into AJCC staging for stage IV disease as a key prognostic factor 3

Pleural Effusion Diagnosis

• LDH is a key component of Light's criteria for distinguishing exudative from transudative pleural effusions 3
• Pleural fluid is considered exudative if:
  • Pleural fluid LDH divided by serum LDH is >0.6
  • Pleural fluid LDH >2/3 the upper limits of laboratory normal value for serum LDH 3

Other Conditions Associated with Elevated LDH

• Myocardial infarction and other forms of tissue damage 1
• Hemolysis (including hemolysis of blood samples) 3
• Infections (bacterial, viral, fungal) 4
• Liver or muscle disease 3

Clinical Implications of Low LDH Levels

• Low LDH levels are not associated with specific pathologies or established diagnostic or prognostic value 7
• Guidelines do not mention low LDH levels as findings requiring evaluation or intervention 7

When to Order LDH Testing

• As part of cancer workup, especially for:
  • Testicular cancer diagnosis and monitoring 3
  • Lymphoma staging and prognosis 5, 2
  • Melanoma staging (stage IV) 3
• Evaluation of pleural effusions (paired with serum LDH) 3
• Investigation of unexplained symptoms when tissue damage is suspected 4

Limitations and Caveats

• LDH is a nonspecific marker as it is present in many tissues; elevation alone has limited diagnostic specificity 1
• LDH isoenzyme fractionation may provide more specific diagnostic information about the source of tissue damage 1
• False elevations can occur with hemolyzed blood samples 3
• Very high isolated LDH (≥800 IU/L) without liver enzyme elevations is associated with significantly higher in-hospital mortality (26.6% vs. 4.3%) and should prompt thorough investigation 4

Prognostic Value

• In cancer patients, elevated LDH often indicates more aggressive disease and poorer prognosis 3, 5
• In hospitalized patients, very high isolated LDH is an independent predictor of mortality and is associated with longer hospital stays and more in-hospital complications 4