What is Lactate Dehydrogenase (LDH) used for?

What is LDH Used For?

Lactate dehydrogenase (LDH) is a widely distributed enzyme used clinically as a nonspecific marker of tissue damage, a prognostic indicator in cancer (particularly testicular germ cell tumors, osteosarcoma, and melanoma), and a key component of Light's criteria for distinguishing exudative from transudative pleural effusions.

Primary Clinical Applications

Cancer Diagnosis and Prognosis

LDH serves as a critical tumor marker in testicular germ cell tumors, where it must be measured alongside AFP and β-HCG before treatment for risk stratification and monitoring. 1, 2

• In testicular cancer, LDH is mandatory for advanced disease and helps determine prognosis, though patients should not be treated based on elevated LDH alone 1, 2
• The International Germ Cell Cancer Collaborative Group classification requires LDH measurement post-orchiectomy and before chemotherapy, with LDH <2.5× upper limit of normal (ULN) indicating good prognosis versus LDH >2.5× ULN defining worse outcomes (3-year progression-free survival of 75-80% vs. 92-93%) 2
• In osteosarcoma, elevated serum LDH correlates with metastatic disease and significantly worse prognosis, with 5-year disease-free survival of 39.5% for high LDH versus 60% for normal values 2
• LDH is incorporated into AJCC staging for stage IV melanoma as a key prognostic factor 2

Pleural Effusion Differentiation

LDH is essential for applying Light's criteria to distinguish exudative from transudative pleural effusions, with 98% sensitivity for identifying exudates. 1

• A pleural effusion is classified as exudative if any one of the following is met: pleural fluid-to-serum LDH ratio >0.6, OR pleural fluid LDH >0.67 (67%) the upper limit of normal serum LDH 1, 2
• When serum is unavailable, pleural fluid LDH >67% the upper limit of normal serum LDH combined with cholesterol >55 mg/dL has equivalent discriminative capacity to Light's criteria 1
• Pleural fluid LDH <250 U/L suggests cardiac origin when combined with albumin gradient >1.2 and bilateral effusion 2

Tissue Damage and Cell Death Detection

LDH release into serum or body fluids indicates plasma membrane breakdown and serves as a general marker of cytotoxicity across various conditions. 1, 3

• LDH is released from cells following tissue injury, with the enzyme widely distributed in heart, liver, skeletal muscle, kidney, and erythrocytes 3, 4
• The test detects enzymatic activity of LDH released by dead cells in culture supernatants or body fluids, though it cannot discriminate between distinct cell death modalities 1
• 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%), and infection (57% vs. 28%) 5

Important Clinical Caveats

Interpretation Limitations

• LDH is a nonspecific marker—numerous benign conditions including liver disease, hemolysis, myocardial infarction, kidney disease, infections, and even strenuous exercise can cause elevation. 2, 3
• LDH stability in supernatants and body fluids, as well as its enzymatic activity, can be affected by several variables including pH and culture medium components 1
• Hemolysis of blood samples can falsely elevate LDH levels 2
• The diagnostic value depends entirely on clinical context and must be interpreted alongside other clinical and laboratory findings 2

Tumor Lysis Syndrome Risk

• Tumor burden reflected by serum LDH is the main predictor for developing tumor lysis syndrome, occurring most frequently in hematologic malignancies with high proliferative rates (Burkitt's lymphoma, B-cell ALL) 2
• Tumor lysis during chemotherapy can cause transient LDH elevation; if levels rise between day 1 of cycle 1 and day 1 of cycle 2, repeat testing midway through cycle 2 is recommended 2

Prognostic Significance

• Very high isolated LDH is an independent predictor of mortality in admitted medical patients, associated with more admission days (9.3 vs. 4.1 days), significantly more in-hospital major complications, and high mortality rate (26.6% vs. 4.3%) 5
• In cancer of unknown primary, a two-factor prognostic score combines ECOG performance status with LDH, where good prognosis requires ECOG 0-1 AND normal LDH 2
• Rising tumor markers (including LDH) soon after therapy completion usually indicate progressive disease requiring salvage therapy 2