What does elevated Lactate Dehydrogenase (LDH) indicate?

Elevated LDH: Clinical Significance and Diagnostic Implications

Elevated lactate dehydrogenase (LDH) indicates tissue damage, increased cellular turnover, or high tumor burden, and serves as both a diagnostic marker for malignancy and a prognostic indicator for disease severity and mortality across multiple conditions. 1

Primary Diagnostic Considerations

Malignancy Assessment

• Elevated LDH is a distinguishing biomarker for cancer, with very high isolated LDH (≥800 IU/mL) associated with malignancy in 27% of cases versus 4% in controls. 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. 3, 1
• LDH is a tumor marker in testicular germ cell tumors used for diagnosis, prognosis, and treatment monitoring, with LDH >2.5× upper limit of normal (ULN) defining worse prognostic categories. 1
• In multiple myeloma, LDH levels help assess tumor cell burden, particularly in lymphoma-like or plasmablastic variants. 3
• Elevated LDH may be an early and only sign of occult malignant lymphoma, warranting thorough investigation including abdominal CT scan. 4

Non-Malignant Causes

• Numerous benign conditions elevate LDH, including liver disease, hemolysis, myocardial infarction, kidney disease, and infections. 1
• Very high isolated LDH is associated with infection in 57% of cases versus 28% in controls. 2
• Strenuous exercise can temporarily elevate LDH due to muscle damage. 1
• In pleural effusions, pleural fluid LDH >2/3 the upper limit of normal serum LDH or pleural fluid LDH/serum LDH ratio >0.6 indicates an exudate by Light's criteria. 1

Prognostic Significance

Mortality and Morbidity Prediction

• Very high isolated LDH is an independent predictor of mortality in admitted medical patients, with mortality rates of 26.6% versus 4.3% in controls. 2
• Patients with very high LDH have significantly more admission days (9.3 vs. 4.1 days) and more in-hospital major complications. 2
• In cancer of unknown primary, elevated LDH combined with ECOG performance status >1 defines poor prognosis. 1

Disease-Specific Prognostic Value

• In testicular germ cell tumors, LDH >1.5× ULN indicates intermediate prognosis, while LDH >10× ULN defines poor prognosis with 5-year overall survival of only 67%. 1
• In stage IV melanoma, elevated LDH is incorporated into AJCC staging as a key prognostic factor. 1
• Elevated LDH reflects high tumor burden and aggressive clinical presentation in plasma cell leukemia. 1

Clinical Algorithm for Interpretation

Degree of Elevation Matters

• Mild elevation (<5× ULN) is most commonly associated with benign causes and requires clinical context for interpretation. 1
• Very high elevation (≥800 IU/mL without concomitant ALT/AST elevation) warrants thorough investigation for metastatic cancer (particularly liver metastases in 14% of cases), hematologic malignancies (5% of cases), or severe infection. 2
• Extreme elevation (>10× normal) carries high mortality risk and is seen in Burkitt's lymphoma, B-cell ALL, and tumor lysis syndrome. 1

Specific Clinical Contexts

• In known cancer patients, use LDH for prognostic stratification per disease-specific guidelines (testicular cancer, osteosarcoma, multiple myeloma). 3, 1
• Measure LDH at initial diagnostic workup for multiple myeloma alongside beta-2 microglobulin to assess tumor cell burden. 3
• In testicular cancer, measure serum LDH shortly after orchiectomy and before any subsequent treatment for risk stratification. 1
• Do NOT use LDH alone to guide treatment decisions, particularly in pure seminoma with involved nodes or metastatic disease. 1

Critical Pitfalls to Avoid

• Hemolysis of blood samples can falsely elevate LDH levels, so repeat testing if hemolysis is suspected. 1
• 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. 1
• The diagnostic value of LDH depends entirely on clinical context and must be interpreted alongside other clinical and laboratory findings, not in isolation. 1
• LDH isoenzyme patterns vary significantly between species and tissues, so total LDH activity alone may be nonspecific without clinical correlation. 5