Elevated LDH Indicates Tissue Damage or Malignancy and Requires Further Investigation
Elevated Lactate Dehydrogenase (LDH) levels indicate tissue damage, increased cellular turnover, or malignancy and warrant thorough investigation for underlying serious conditions including cancer, infection, or tissue infarction. 1
Clinical Significance of Elevated LDH
Lactate dehydrogenase is an enzyme found in nearly all body tissues that catalyzes the interconversion of lactate and pyruvate. When cells are damaged or destroyed, LDH is released into the bloodstream, causing serum levels to rise. The clinical significance varies based on the degree of elevation:
- Moderate elevation: May indicate various conditions including tissue injury, inflammation, or early disease
- Very high elevation (≥800 IU/L): Strong marker for cancer and associated with higher mortality 1, 2
- Extreme elevation (>10-fold normal): Associated with poor prognosis regardless of cause (mortality >50%) 1
Conditions Associated with Elevated LDH
Malignancies
- Hematologic malignancies: Lymphomas, leukemias, multiple myeloma 3, 4
- Solid tumors with metastasis: Particularly melanoma, testicular cancer 5
- Bone cancer: Osteosarcoma 5
- Plasma cell disorders: Primary plasma cell leukemia 5
Non-malignant Conditions
- Tissue injury: Myocardial infarction, pulmonary infarction, muscle trauma
- Hemolysis: Hemolytic anemia, sickle cell crisis
- Infections: Severe pneumonia, sepsis
- Liver disease: Hepatitis, cirrhosis
- Renal disease: Acute kidney injury
LDH Isoenzymes and Their Significance
LDH exists in five different isoenzymes (LDH1-LDH5), each predominant in different tissues 1, 6:
| Isoenzyme | Predominant Location | Associated Conditions When Elevated |
|---|---|---|
| LDH1 & LDH2 | Heart, RBCs, kidneys | Myocardial infarction, hemolysis, renal infarction |
| LDH3 | Lungs, lymphatic tissue | Pulmonary disease, lymphomas |
| LDH4 | Placenta, kidneys | Pregnancy-related conditions |
| LDH5 | Liver, skeletal muscle | Liver disease, muscle injury |
Prognostic Value in Specific Diseases
- Melanoma: Elevated LDH is incorporated into the AJCC staging system for stage IV disease and indicates worse prognosis 5, 1
- Testicular cancer: Elevated LDH correlates with tumor burden and is used for risk stratification 5
- Multiple myeloma: High LDH levels identify an aggressive "high-grade myeloma" with features of extraosseous disease 4
- Osteosarcoma: Elevated LDH correlates with worse 5-year disease-free survival rates 5
- Plasma cell leukemia: Reflects high tumor burden and aggressive clinical presentation 5
Evaluation of Elevated LDH
When elevated LDH is detected, the following workup is recommended 1, 2:
- Complete blood count with differential: To evaluate for anemia, hemolysis, or hematologic malignancies
- Comprehensive metabolic panel: Including liver and renal function tests
- Additional laboratory tests based on clinical suspicion:
- Tumor markers (AFP, β-HCG) for suspected germ cell tumors
- S-100 protein for melanoma
- Imaging studies based on clinical findings:
- Chest radiograph
- Abdominal ultrasound
- CT or MRI for suspected malignancy
Monitoring and Treatment Implications
- In patients with known malignancy, serial LDH measurements help monitor treatment response 1
- Rising levels may indicate disease progression or treatment failure
- Normalization of previously elevated LDH may indicate effective treatment
- Very high isolated LDH (≥800 IU/L) is associated with longer hospital stays and higher mortality rates 2
Caveats and Limitations
- LDH lacks specificity and must be interpreted in clinical context
- Serial measurements are more valuable than single readings
- LDH elevation reflects existing tumor burden but cannot predict recurrence in tumor-free patients
- Patients should not be treated based solely on elevated LDH without further investigation 1
- False elevations can occur with hemolysis during blood collection
Key Takeaway
An elevated LDH level should never be dismissed as insignificant. It warrants thorough investigation, especially when markedly elevated, as it may be the earliest indicator of serious underlying pathology, particularly occult malignancy 2, 3.