Diagnostic and Prognostic Applications of Lactate Dehydrogenase (LDH)
Lactate dehydrogenase (LDH) is primarily used as a biomarker for tissue damage, disease monitoring, and prognostic assessment in various clinical conditions, with particular value in cancer staging, cardiac evaluation, and distinguishing between exudative and transudative pleural effusions. 1
Primary Clinical Applications of LDH
Cancer Diagnosis and Monitoring
- Mandatory tumor marker for advanced germ cell tumors, used alongside AFP and β-HCG 2
- Serves as an important prognostic factor in testicular cancer 2
- Elevated LDH correlates with poor prognosis in solid tumors and hematologic malignancies 1
- Serial measurements help monitor treatment response in cancer patients - normalization suggests treatment response while elevation indicates progression 1
- Not recommended for surveillance in early-stage cancers (stages I-III) due to lack of specificity 1
Pleural Fluid Analysis
- Used to distinguish between exudative and transudative pleural effusions (Light's criteria) 2
- In pleural fluid analysis, LDH >67% of the upper limit of normal serum LDH suggests an exudate 2
Tissue Damage Assessment
- Elevated serum LDH indicates tissue damage as cells release intracellular enzymes through damaged cell membranes 3
- Very high isolated LDH (≥800 IU/ml) warrants thorough investigation for severe underlying disease, particularly:
- Metastatic cancer (14% vs. 3% in controls)
- Hematologic malignancies (5% vs. 0% in controls)
- Infections (57% vs. 28% in controls) 4
Prognostic Value
- Independent predictor of mortality in hospitalized medical patients 4
- Associated with more hospital complications and longer hospital stays 4
- Elevated LDH correlates with reduced response to treatment in cancer patients 1
Laboratory Considerations
Testing Recommendations
- Should be interpreted in context with other clinical and laboratory findings due to low specificity 1
- Serial measurements provide greater value than single determinations 1
- No longer recommended as a standalone test for evaluation of cardiac injury (replaced by troponin) 2
Analytical Issues
- Desirable imprecision (expressed as %CV) of LDH assays has been defined as 10% CV at the 99th percentile reference limit 2
- Clinical laboratories should validate reference intervals based on peer-reviewed literature 2
Specific Disease Applications
Germ Cell Tumors
- Mandatory marker for advanced disease alongside AFP and β-HCG 2
- Important for risk classification in testicular germ cell tumors 2
- Used for diagnosis, prognosis, and monitoring treatment response 2
Cell Death Assessment
- Used in research settings to monitor cell death in laboratory studies 2
- In cytotoxicity assays, LDH release indicates plasma membrane breakdown 2
Other Clinical Applications
- Helpful in differential diagnosis of ascites (malignant vs. non-malignant) 5
- Used in diagnosis of glycogen storage diseases 1
- Elevated in inflammatory diseases and associated with mortality risk in COVID-19 6
Clinical Approach to Elevated LDH
Initial Evaluation
- Complete blood count with differential
- Liver and renal function tests
- Inflammatory markers (CRP, ESR, ferritin)
- D-dimer
- Cardiac markers if cardiac involvement 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
Cautions and Limitations
- Low specificity as a standalone test - elevated in numerous conditions 1, 7
- Patients should not be treated based solely on elevated LDH 1
- LDH activity can be affected by sample handling, pH, and components in culture medium 2
- LDH patterns vary significantly between species, limiting cross-species application 7