What is the purpose of Lactate Dehydrogenase (LDH)?

Purpose of Lactate Dehydrogenase (LDH)

LDH serves three primary clinical purposes: as a marker of tissue damage and cell death, as a tumor marker for diagnosis and prognosis in multiple cancers, and as a diagnostic tool to differentiate between exudative and transudative pleural effusions. 1, 2

Biochemical Function

LDH is an oxidoreductase enzyme that catalyzes the reversible conversion of pyruvate to lactate with NAD+/NADH as a coenzyme system, representing the terminal step in anaerobic glycolysis. 3, 4 This enzyme is widely distributed across body tissues, with highest concentrations in heart, liver, skeletal muscle, kidney, and erythrocytes. 3

Clinical Diagnostic Applications

Tissue Damage and Cell Death Detection

• LDH release into serum indicates plasma membrane breakdown and cellular injury, making it a nonspecific but useful marker of cytotoxicity across multiple organ systems. 5
• The enzyme's activity in culture supernatants or body fluids serves as a spectrophotometric indicator of cell death, though this test cannot discriminate among distinct cell death modalities. 5
• Elevated serum LDH reflects tissue damage or increased cellular turnover from conditions including hemolysis, liver disease, myocardial infarction, kidney disease, and infections. 2

Cancer Diagnosis and Prognosis

LDH functions as a critical tumor marker in multiple malignancies, with specific prognostic thresholds established by major cancer societies:

• In testicular germ cell tumors, LDH is measured alongside AFP and β-HCG for diagnosis, risk stratification, and treatment monitoring, with LDH >2.5× upper limit of normal (ULN) defining worse prognosis (3-year progression-free survival 75-80% versus 92-93% for good-prognosis group). 5, 2
• In osteosarcoma, elevated LDH correlates with metastatic disease and significantly worse outcomes (5-year disease-free survival 39.5% versus 60% for normal values). 2
• In melanoma, elevated LDH is incorporated into AJCC staging for stage IV disease as a key prognostic factor. 2
• Elevated LDH reflects high tumor burden in plasma cell leukemia and predicts tumor lysis syndrome risk in hematologic malignancies with high proliferative rates. 1, 2

Pleural Effusion Differentiation

The European Respiratory Society and British Thoracic Society recommend LDH as a key component of Light's criteria to distinguish exudative from transudative pleural effusions with 98% sensitivity and 72% specificity. 1

• Pleural fluid is exudative if pleural fluid LDH/serum LDH ratio >0.6, or if pleural fluid LDH >2/3 the upper limit of normal serum LDH. 1, 2
• Pleural fluid LDH <250 U/L suggests cardiac origin when combined with albumin gradient >1.2 and bilateral effusion. 2

Important Clinical Caveats

• LDH is a nonspecific marker—elevated levels occur in numerous benign conditions including strenuous exercise, making interpretation dependent on clinical context. 2
• LDH enzymatic activity decreases over time due to natural degradation and is affected by pH and culture medium components, requiring timely measurement. 5
• Hemolysis of blood samples can falsely elevate LDH levels. 2
• In testicular cancer, patients should not be treated based on elevated LDH alone, and post-orchiectomy LDH should not be used to stage pure seminoma with involved nodes or metastatic disease. 2
• When tumor lysis during chemotherapy causes transient LDH elevation between day 1 of cycle 1 and day 1 of cycle 2, repeat testing midway through cycle 2 is recommended. 2