What are the causes of elevated Lactate Dehydrogenase (LDH) levels?

Causes of Elevated Lactate Dehydrogenase (LDH) Levels

Elevated LDH levels are associated with various clinical conditions including malignancies, infections, cardiac conditions, liver disorders, muscle disorders, and renal conditions, with the degree of elevation often correlating with disease severity and mortality risk. 1

Major Categories of LDH Elevation

Malignancies

• Hematologic malignancies: Often cause markedly elevated LDH (>900 IU/L) 1
  • Malignant lymphomas - can present with elevated LDH even in occult/preclinical stages 2
  • Multiple myeloma - high-grade myeloma with aggressive features often shows LDH >300 IU/L 3
• Solid tumors:
  • Metastatic cancer, particularly liver metastases (14% of cases with very high LDH) 4
  • Advanced stage cancers - LDH serves as both a diagnostic marker and prognostic indicator 5

Infections

• Represent 57% of cases with very high isolated LDH (≥800 IU/L) 4
• Various bacterial, viral, and fungal infections can cause LDH elevation
• Severity of infection often correlates with degree of LDH elevation

Tissue Damage

• Cardiac conditions:
  • Myocardial infarction
  • Heart failure
• Liver disorders:
  • Hepatitis
  • Cirrhosis
• Muscle disorders:
  • Rhabdomyolysis
  • Muscular dystrophies
  • Trauma
• Pulmonary conditions:
  • Pulmonary embolism
  • Pneumonia
• Hemolytic conditions:
  • Hemolytic anemia
  • Thrombotic thrombocytopenic purpura

Clinical Significance of LDH Elevation

Diagnostic Value

• Very high isolated LDH (≥800 IU/L) is a distinguishing biomarker for:
  • Cancer (27% vs. 4% in controls) 4
  • Liver metastases (14% vs. 3%) 4
  • Hematologic malignancies (5% vs. 0%) 4
  • Infections (57% vs. 28%) 4

Prognostic Value

• Very high LDH is associated with:
  • Longer hospital stays (9.3 vs. 4.1 days) 4
  • More in-hospital complications 4
  • Higher mortality rate (26.6% vs. 4.3%) 4
  • Independent predictor of mortality in hospitalized patients 4
• In cancer patients, elevated LDH indicates:
  • More aggressive disease 5
  • Poorer response to treatment 5
  • Shorter survival time 3

Evaluation Approach for Elevated LDH

1. Initial laboratory evaluation:

   • Complete blood count with differential
   • Liver function tests
   • Renal function tests
   • Inflammatory markers (CRP, ESR)
   • Cardiac markers if cardiac etiology suspected (troponin, BNP/NT-proBNP)
   • D-dimer
   • Serum ferritin 1

2. Imaging studies:

   • Chest radiograph
   • Abdominal ultrasound to evaluate liver, spleen, and lymph nodes
   • Consider echocardiography if cardiac symptoms present 1
   • Advanced imaging (CT, PET) if malignancy suspected 1

3. Specialized testing:

   • Blood cultures if infection suspected
   • Tumor markers if malignancy suspected
   • LDH isoenzyme analysis to determine source of elevation 1

Clinical Pearls and Pitfalls

• Pearl: LDH isoenzyme analysis can help narrow the differential diagnosis when the source of elevation is unclear 1
• Pearl: Serial measurements of LDH can help monitor disease progression and treatment efficacy 1
• Pitfall: Patients should not be treated based solely on an elevated LDH without identifying the underlying cause 1
• Pitfall: Even normal-high LDH levels in newly diagnosed myeloma patients may suggest presence of an aggressive tumor subpopulation with poorer prognosis 3
• Pitfall: LDH elevations can be influenced by treatments such as blood transfusions, growth factors, radiotherapy, and chemotherapy 6

When to Be Particularly Concerned

• LDH elevations >10 times normal range carry a particularly poor prognosis with mortality rates >50% 6
• Unexplained LDH elevations warrant thorough investigation for occult malignancy, including consideration of abdominal CT scan 2
• In patients with known malignancy, rising LDH levels may indicate disease progression or treatment failure 6