What is the normal serum lactate dehydrogenase (LDH) range in adults and how should an abnormal LDH result be evaluated?

Normal LDH Range and Evaluation of Abnormal Results

The normal serum LDH range in adults is approximately 140-280 U/L (though this varies by laboratory), and an abnormal result requires systematic evaluation based on the degree of elevation and clinical context, prioritizing assessment for malignancy, hemolysis, tissue ischemia, and organ damage. 1

Normal Reference Range

• The upper limit of normal (ULN) for serum LDH typically falls between 250-280 U/L in most clinical laboratories, though specific reference ranges vary by institution and assay method 1, 2
• LDH exists as five isoenzymes (LDH1-LDH5) with different tissue distributions: LDH1 and LDH2 predominate in heart and red blood cells, LDH3 in lungs, and LDH4-LDH5 in liver and skeletal muscle 2, 3

Stratification by Degree of Elevation

Mild Elevation (<5× ULN, approximately <1,400 U/L)

• Most commonly associated with benign causes including liver disease, hemolysis, myocardial infarction, kidney disease, infections, and strenuous exercise 1
• Order hepatic function tests (ALT, AST, alkaline phosphatase, total bilirubin) to identify hepatitis, cirrhosis, or biliary obstruction 1
• Repeat the LDH measurement if the blood sample appears hemolyzed, as in-vitro hemolysis falsely elevates LDH values 1
• Review medication history for drug-induced liver injury 1

Moderate Elevation (5-10× ULN, approximately 1,400-2,800 U/L)

• In males with unexplained LDH >1.5× ULN (approximately >450 U/L), measure serum AFP and β-hCG because this level carries prognostic significance for testicular germ cell tumors 1
• Consider hematologic malignancies, particularly if accompanied by cytopenias or lymphadenopathy 1, 4
• Evaluate for metastatic solid tumors, especially liver metastases (14% prevalence in patients with very high isolated LDH) 4

Severe Elevation (>10× ULN, approximately >2,800 U/L)

• Carries high mortality risk and warrants urgent evaluation for tumor lysis syndrome, particularly in Burkitt's lymphoma, B-cell ALL, and bulky small cell lung cancer 1
• Measure serum uric acid, potassium, phosphate, calcium, and creatinine to assess for tumor lysis syndrome 1
• Very high isolated LDH (≥800 U/L without concomitant ALT/AST elevation) is an independent predictor of mortality with 26.6% in-hospital death rate 4

Disease-Specific Diagnostic Applications

Malignancy Assessment

• Do not rely on LDH alone to diagnose cancer; combine with disease-specific markers (AFP/β-hCG for testicular cancer, β-2 microglobulin for multiple myeloma) to improve specificity 1
• 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 osteosarcoma, elevated LDH correlates with metastatic disease and worse prognosis: 5-year disease-free survival of 39.5% versus 60% for normal values 1
• In multiple myeloma staging (Revised ISS), elevated LDH combined with β2-microglobulin >5.5 mg/L or high-risk FISH abnormalities defines stage III disease 5
• In stage IV melanoma, elevated LDH is incorporated into AJCC staging as an independent predictor of poor outcome 1

Pleural Effusion Characterization

• Pleural fluid is exudative if pleural fluid LDH/serum LDH ratio >0.6, OR if pleural fluid LDH >2/3 the ULN for serum LDH (Light's criteria) 5, 1
• Pleural fluid LDH <250 U/L suggests cardiac origin when albumin gradient >1.2 g/dL and effusion is bilateral 1
• In secondary peritonitis from perforated viscus, ascitic LDH levels exceed serum LDH levels 1

Hemolysis Detection

• Check LDH isoenzymes if hemolysis is suspected: disproportionate elevation of LDH1 and LDH2 indicates red blood cell destruction 3
• However, in thrombotic thrombocytopenic purpura (TTP), LDH5 (liver/skeletal muscle origin) is consistently elevated 1-2 fold, while LDH1/LDH2 are not disproportionately increased, suggesting systemic ischemic tissue damage rather than pure hemolysis 3
• In patients with mechanical circulatory support devices, LDH elevation >2.5× ULN requires evaluation for pump thrombosis 1

Infection and Inflammation

• Infections (viral, tuberculous) and autoimmune conditions typically present with normal or only mildly elevated LDH 6
• In community-acquired pneumonia, quantitative bacterial culture of bronchoalveolar lavage fluid with LDH measurement helps distinguish infection from colonization 5
• In febrile neutropenia with myelodysplastic syndromes, markedly rising LDH suggests progression to acute leukemia and warrants intensification to hypomethylating agents (azacitidine or decitabine) 1

Critical Pitfalls to Avoid

• Never use LDH concentrations alone to guide treatment decisions, particularly in pure seminoma where post-orchiectomy LDH should not determine staging or prognosis 1
• Tumor lysis during chemotherapy causes 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
• Strenuous exercise temporarily elevates LDH due to muscle damage—consider timing of blood draw relative to physical activity 1
• In pregnancy, LDH elevation requires evaluation for preeclampsia, particularly when accompanied by hypertension and proteinuria 1

Algorithmic Approach to Abnormal LDH

1. Confirm validity: Rule out hemolyzed specimen and repeat if necessary 1
2. Quantify elevation: Mild (<5× ULN), moderate (5-10× ULN), or severe (>10× ULN) 1
3. Assess clinical context:
   • Cancer history or suspicion → measure disease-specific tumor markers 1
   • Pleural effusion → apply Light's criteria with pleural fluid LDH 5, 1
   • Suspected hemolysis → check LDH isoenzymes, haptoglobin, indirect bilirubin 3
   • High tumor burden → assess tumor lysis syndrome risk with uric acid, electrolytes 1
4. Order targeted imaging: CT chest/abdomen/pelvis for suspected malignancy or lymphadenopathy 6
5. Consider tissue diagnosis: Excisional lymph node biopsy or bone marrow biopsy when indicated 6