What does Lactate Dehydrogenase (LDH) indicate?

What Does LDH Tell Us?

Lactate dehydrogenase (LDH) is a nonspecific marker of cellular damage and tissue breakdown that serves multiple clinical roles: it indicates tumor burden and prognosis in malignancies, helps differentiate pleural effusion types, and signals tissue injury from diverse causes including hemolysis, organ damage, and infection. 1

Primary Clinical Applications

Cancer Prognostication and Monitoring

LDH is most clinically valuable as a prognostic marker in specific malignancies where elevated levels consistently predict worse outcomes:

• In testicular germ cell tumors, LDH is a required tumor marker for risk stratification, with levels >2.5× upper limit of normal (ULN) defining poorer prognosis groups (3-year progression-free survival 75-80% versus 92-93% for good-prognosis patients with LDH <2.5× ULN) 1

• In melanoma stage IV disease, elevated LDH is incorporated into AJCC staging as a key prognostic factor and should be measured at diagnosis, though it is not sensitive for detecting metastatic disease 2, 1

• In multiple myeloma, LDH helps assess tumor cell burden, particularly in lymphoma-like or plasmablastic presentations; elevated levels predict drug resistance (only 20% response rate versus 57% with normal LDH) and short survival (median 9 months versus longer survival with normal levels) 2, 3

• In osteosarcoma, elevated serum LDH correlates with metastatic disease and dramatically worse prognosis (5-year disease-free survival 39.5% versus 60% for normal values) 1

Pleural Effusion Diagnosis

LDH is a key component of Light's criteria for distinguishing exudative from transudative pleural effusions:

• Pleural fluid is exudative if pleural fluid LDH ÷ serum LDH is >0.6, OR if pleural fluid LDH is >2/3 the upper limits of normal for serum LDH 1

Cell Death and Tissue Damage Detection

LDH release indicates plasma membrane breakdown and cytotoxicity, making it useful for detecting cell death in various contexts:

• LDH activity in culture supernatants or body fluids signals loss of cellular integrity, though it cannot discriminate among distinct cell death modalities (apoptosis versus necrosis) 2

• Very high isolated LDH (≥800 IU/mL) in hospitalized patients is a distinguishing biomarker for metastatic cancer (27% versus 4% in controls), hematologic malignancies (5% versus 0%), and severe infection (57% versus 28%), and independently predicts mortality (26.6% versus 4.3%) 4

Interpretation Caveats and Limitations

Nonspecificity Requires Clinical Context

Because LDH is present in essentially all major organ systems, elevated total LDH is nonspecific and must be interpreted alongside clinical findings:

• Numerous benign conditions cause LDH elevation: liver disease, hemolysis, myocardial infarction, kidney disease, infections, and even strenuous exercise from muscle damage 1

• Hemolysis of blood samples can falsely elevate LDH levels 1

• The diagnostic value depends entirely on clinical context and should be interpreted with other laboratory findings 1

Enzymatic Activity Limitations

LDH measurement has inherent technical limitations:

• LDH activity decreases over time due to natural enzymatic degradation 2

• pH and specific culture medium components can affect measured activity 2

• Tumor lysis during chemotherapy causes transient elevation; if LDH rises between day 1 of cycle 1 and day 1 of cycle 2, repeat testing midway through cycle 2 is recommended 1

Clinical Decision Algorithm

When encountering elevated LDH, follow this approach:

1. Assess the degree of elevation: Mild elevation (<5× ULN) is most commonly benign, while severe elevation (>10× normal) carries high mortality risk 1

2. Consider the clinical context:

   • Known cancer patients: Use LDH for prognostic stratification per disease-specific guidelines 1
   • Pleural effusion: Apply Light's criteria 1
   • Hospitalized patients with very high isolated LDH (≥800 IU/mL): Investigate for metastatic cancer, hematologic malignancies, and severe infection 4

3. Rule out common benign causes: Check for hemolysis, recent strenuous exercise, liver disease, myocardial infarction, and medication effects 1

4. Do NOT use LDH alone for treatment decisions: In testicular cancer, patients should not be treated based on elevated LDH alone; in seminoma with involved nodes or metastatic disease, do not use post-orchiectomy LDH for staging or prognosis 1

5. Monitor appropriately: Measure LDH when treatment concludes, as rising tumor markers soon after therapy indicate progressive disease requiring salvage therapy 1