What is LDH (Lactate Dehydrogenase) Marker?
LDH is an enzyme found in nearly all body tissues that serves as a nonspecific biomarker of tissue damage, cell death, and increased cellular turnover, with critical applications in cancer diagnosis, prognosis, and monitoring, as well as in distinguishing types of pleural effusions.
Biochemical Function
LDH catalyzes the reversible conversion of lactate to pyruvate (and vice versa) using NAD+/NADH as a coenzyme system, representing the final step in glycolysis. 1, 2
The enzyme exists as five isoenzyme forms (LDH-1 through LDH-5) composed of two subunit types (H and M), creating tetrameric structures: LDH-H4, -H3M1, -H2M2, -H1M3, and -M4. 3
Different tissues contain varying proportions of these isoenzymes, which allows for tissue-specific identification when LDH is elevated—though routine isoenzyme testing is not recommended in most clinical scenarios. 4, 5
Primary Clinical Applications in Cancer
Testicular Germ Cell Tumors
LDH is mandatory for all patients with testicular cancer alongside AFP and β-HCG, serving critical roles in diagnosis, risk stratification, and treatment monitoring. 4
Measure LDH before orchiectomy and again after surgery to establish half-life kinetics (normal half-life approximately 3-5 days), which helps distinguish persistent disease from normal clearance. 4, 6
For advanced testicular cancer, LDH levels determine prognostic groups: good prognosis requires LDH <1.5× upper limit of normal (ULN), intermediate prognosis is LDH 1.5-10× ULN, and poor prognosis is LDH >10× ULN. 6
LDH is less specific than AFP and β-HCG but remains an independent prognostic factor—never use LDH elevation alone to guide treatment decisions in pure seminoma. 4, 6
Other Malignancies
In osteosarcoma, elevated LDH correlates with metastatic disease and significantly worse outcomes: 5-year disease-free survival of 39.5% with high LDH versus 60% with normal values. 6
For stage IV melanoma, elevated LDH is incorporated into AJCC staging as an independent predictor of poor outcome. 6
Elevated LDH reflects high tumor burden in plasma cell leukemia, multiple myeloma (measured at diagnosis alongside β-2 microglobulin), and lymphomas. 6, 7
Pleural Effusion Diagnosis
LDH is a key component of Light's criteria for distinguishing exudative from transudative pleural effusions with 98% sensitivity and 72% specificity. 7
Pleural fluid is exudative if: (1) pleural fluid LDH/serum LDH ratio >0.6, OR (2) pleural fluid LDH >2/3 the upper limit of normal for serum LDH. 6, 7
Pleural fluid LDH <250 U/L suggests cardiac origin when combined with albumin gradient >1.2 and bilateral effusion. 6
Non-Malignant Causes of Elevation
Numerous benign conditions elevate LDH, including hemolysis (in vivo or in vitro), liver disease, myocardial infarction, kidney disease, infections, and strenuous exercise. 6
Always repeat LDH measurement if the blood sample appears hemolyzed, as in-vitro hemolysis falsely elevates values. 6
Secondary peritonitis from perforated viscus shows ascitic LDH levels higher than serum LDH levels. 6
Tumor Lysis Syndrome Risk Assessment
Tumor burden reflected by serum LDH is the main predictor for developing tumor lysis syndrome, particularly in Burkitt's lymphoma, B-cell ALL, and bulky small cell lung cancer. 6
In mantle-cell lymphoma with high tumor burden, measure serum LDH to evaluate spontaneous tumor lysis syndrome risk and include serum uric acid measurement. 6
Practical Interpretation Algorithm
When LDH is Mildly Elevated (1.5-5× ULN):
Order hepatic function tests (ALT, AST, alkaline phosphatase, total bilirubin) to identify hepatitis, cirrhosis, or biliary obstruction. 6
In males with unexplained LDH >1.5× ULN, include serum AFP and β-HCG testing because this level carries prognostic significance for testicular tumors. 6
Consider medication review for drug-induced liver injury, though this is an uncommon cause. 6
When LDH is Markedly Elevated (>10× ULN):
This carries high mortality risk and suggests massive tissue destruction, severe hemolysis, or high-grade malignancy. 6
Evaluate for tumor lysis syndrome in cancer patients, particularly those with hematologic malignancies. 6
Critical Pitfalls to Avoid
Never diagnose cancer based on LDH alone—always combine with disease-specific markers (AFP/β-HCG for testicular cancer, β-2 microglobulin for myeloma) to improve specificity. 6
Do not use post-orchiectomy LDH to stage or predict prognosis in seminoma patients with involved nodes or metastatic disease. 6
Recognize that 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. 6
The diagnostic value of LDH depends entirely on clinical context—interpret alongside other clinical and laboratory findings rather than in isolation. 6