What is LDH (Lactate Dehydrogenase)?
LDH is an intracellular enzyme that catalyzes the reversible conversion of lactate to pyruvate (and vice versa) during glucose metabolism, and when measured in blood, serves as a nonspecific marker of tissue damage, cell turnover, and disease severity across multiple organ systems. 1, 2
Biochemical Function
LDH exists as five different isoenzymes (LDH-1 through LDH-5) formed from combinations of two subunit types (M and H), with each isoform having distinct tissue distribution and biochemical properties. 2, 3
The enzyme is predominantly cytoplasmic but has multi-organellar locations, playing a central role in both aerobic and anaerobic cellular metabolism by maintaining the NAD+/NADH coenzyme system. 2
LDH is normally present in high concentrations within cells of the heart, liver, skeletal muscle, kidney, and red blood cells, with lower amounts in lung, smooth muscle, and brain. 3
Clinical Measurement and Interpretation
Serum LDH is measured using enzymatic activity assays that detect the conversion of lactate to pyruvate or vice versa, with results highly dependent on assay method and laboratory-specific reference ranges. 1
Elevated LDH is defined as levels exceeding 1.5 times the laboratory-specific upper limit of normal (ULN), though this threshold varies by clinical context. 1, 4
The enzyme has no biological half-life in the traditional sense since it reflects ongoing cellular release rather than clearance of a secreted protein. 2
Why LDH Becomes Elevated
Any process causing tissue damage or increased cellular turnover releases intracellular LDH into the bloodstream, making it a nonspecific marker that can be elevated in both malignant and benign conditions. 1, 2
Common benign causes include hemolysis (including artifactual from blood sample handling), myocardial infarction, liver disease (hepatitis, cirrhosis, biliary obstruction), muscle disease, kidney disease, and infections. 1, 4
Malignant conditions frequently associated with elevated LDH include lymphoma, small-cell lung cancer, Ewing sarcoma, osteogenic sarcoma, germ cell tumors, and metastatic disease. 1
Very high isolated LDH (≥800 IU/mL) is a distinguishing biomarker for metastatic cancer (particularly liver metastases), hematologic malignancies, and severe infections, and independently predicts mortality in hospitalized patients. 5
Clinical Applications in Cancer
In testicular germ cell tumors, LDH serves as a mandatory prognostic marker (not diagnostic) and should be measured in advanced disease alongside AFP and β-HCG, with levels >1.5× ULN indicating worse prognosis. 1, 6
LDH cannot distinguish between seminoma and nonseminoma (both tumor types can elevate it), making it useless for histologic discrimination—only AFP provides this distinction. 6
In stage IV melanoma, serum LDH is incorporated into AJCC staging as a key prognostic factor, with elevated levels defining the M1c category (worst prognosis) regardless of metastatic site. 1, 4
In osteosarcoma, elevated LDH correlates with metastatic disease at presentation and significantly worse outcomes, with 5-year disease-free survival of 39.5% versus 60% for normal values. 4
Critical Limitations and Pitfalls
Because LDH is widely distributed across all tissues, an elevated total LDH is a nonspecific finding that requires clinical context and additional testing to determine the underlying cause. 1, 3
Hemolysis of blood samples is a common cause of falsely elevated LDH and must be excluded before clinical interpretation. 1, 4
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 is necessary to distinguish tumor progression from lysis. 1, 4
LDH should never be used alone to guide treatment decisions—it must be interpreted alongside other clinical findings, imaging, and disease-specific markers. 1, 4
Prognostic Value Across Diseases
In cancer patients, elevated LDH generally indicates higher tumor burden, more aggressive disease biology, and poorer prognosis across multiple tumor types. 4, 7
The degree of LDH elevation matters: mild elevation (<5× ULN) is most commonly benign, while severe elevation (>10× normal) carries high mortality and warrants urgent investigation for life-threatening conditions like tumor lysis syndrome. 4
In hospitalized medical patients, very high isolated LDH (≥800 IU/mL) is associated with significantly more admission days (9.3 vs 4.1 days), major in-hospital complications, and mortality (26.6% vs 4.3%). 5