What is the normal reference range for serum lactate dehydrogenase (LDH) and which conditions can cause an elevated LDH level?

Serum Lactate Dehydrogenase (LDH): Normal Range and Causes of Elevation

Normal Reference Range

The normal reference range for serum LDH is laboratory-specific and depends on the assay methodology employed, but the upper limit of normal (ULN) typically falls between 200-250 U/L in most clinical laboratories. 1

• LDH activity is quantified by spectrophotometric monitoring of the reversible conversion of lactate to pyruvate using NAD⁺/NADH as a co-enzyme 1
• The test may be ordered as "LDH," "total LDH," or "lactic acid dehydrogenase" 1
• Total LDH measurement reflects combined enzymatic activity from all tissue sources 1

Conditions Causing Elevated LDH

Malignancies (Most Clinically Significant)

Hematologic malignancies are among the most common causes of marked LDH elevation, particularly those with high proliferative rates. 2

• Burkitt's lymphoma and B-cell acute lymphoblastic leukemia carry the highest risk for extreme LDH elevation due to high proliferative rates and tumor sensitivity to chemotherapy 3
• Other B-cell non-Hodgkin's lymphomas and T-cell ALL can produce marked elevations 3
• Plasma cell leukemia shows elevated LDH associated with high tumor burden and aggressive clinical presentation 1
• Testicular germ cell tumors use LDH for risk stratification: LDH >1.5× ULN indicates intermediate prognosis in non-seminomatous tumors, while LDH >10× ULN defines poor prognosis with 5-year overall survival of only 67% 3
• Osteosarcoma patients with elevated LDH have 5-year disease-free survival of 39.5% versus 60% for those with normal values, and elevated LDH correlates with metastatic disease 3
• Stage IV melanoma incorporates elevated LDH into AJCC staging as a key prognostic factor 3
• Bulky small cell lung cancer and metastatic germ cell carcinoma are high-risk solid tumors for LDH elevation 3

Tissue Damage and Organ Injury

Hemolysis causes LDH elevation in combination with decreased haptoglobin and elevated indirect bilirubin. 2

• Myocardial infarction releases LDH from damaged cardiac tissue 2
• Liver disease of various etiologies elevates LDH, though this is nonspecific 2
• Muscle damage from strenuous exercise or rhabdomyolysis temporarily elevates LDH 2, 3
• Kidney disease contributes to elevated LDH levels 2

Infections and Inflammatory Conditions

Sepsis and septic shock can elevate LDH levels in critically ill patients. 2

• Infections of various types can cause LDH elevation 2, 4
• Very high isolated LDH (≥800 IU/mL) is a distinguishing biomarker for infection (57% vs. 28% in controls) 4

Pleural and Peritoneal Fluid Disorders

Exudative pleural effusions show pleural fluid LDH >2/3 the upper limit of normal serum LDH or pleural fluid LDH/serum LDH ratio >0.6 by Light's criteria. 2, 1

• Pleural fluid LDH <250 U/L suggests cardiac origin when other criteria are met (albumin gradient >1.2, bilateral effusion) 3
• Secondary peritonitis from perforated viscus shows ascitic LDH levels higher than serum LDH levels 2, 3

Pregnancy-Related Causes

Preeclampsia causes LDH elevation and requires evaluation for underlying pathological processes in pregnant women. 2, 3

Iatrogenic and Device-Related Causes

Mechanical circulatory support devices cause baseline hemolysis with LDH elevation; levels >2.5 times ULN require evaluation for pump thrombosis. 2, 3

• Tumor lysis syndrome occurs spontaneously or after treatment with corticosteroids, monoclonal antibodies, or chemotherapeutic agents, particularly in high tumor burden malignancies 2, 3
• Drug-induced liver injury is an uncommon cause of mild aminotransferase and LDH elevation 2

Laboratory Artifact

Hemolysis of blood samples can falsely elevate LDH levels and requires repeat testing. 2, 3

Interpretation by Degree of Elevation

Mild LDH elevation (<5× ULN) is most commonly associated with benign causes, including liver disease, hemolysis, myocardial infarction, kidney disease, muscle damage, and infections. 2, 3

• Extreme LDH elevation (>10× normal) carries a poor prognosis with high mortality rate, regardless of benign or malignant etiology 2
• Very high isolated LDH (≥800 IU/mL) is associated with 26.6% mortality rate versus 4.3% in controls and is an independent predictor of mortality 4

Critical Diagnostic Pitfalls

Clinical context is essential: LDH must be interpreted alongside other clinical and laboratory findings, never in isolation. 2, 3

• LDH has low specificity since it may be elevated due to numerous reasons 5
• In males with unexplained LDH >1.5× ULN, include serum AFP and β-hCG testing because LDH at this level carries prognostic significance for germ-cell tumors 3
• Do not rely on LDH alone to diagnose cancer; combine LDH with disease-specific markers to improve specificity 3
• Assess hepatic function when LDH is mildly elevated by ordering ALT, AST, alkaline phosphatase, and total bilirubin 3