What does an isolated elevation of lactate dehydrogenase (LDH) in a 31-year-old woman indicate?

Isolated LDH Elevation in a 31-Year-Old Woman

An isolated elevation of lactate dehydrogenase (LDH) in a 31-year-old woman most commonly indicates hemolysis, tissue injury, or occult malignancy, and requires immediate confirmation that the sample was not hemolyzed in vitro, followed by targeted evaluation based on the degree of elevation and clinical context. 1

Initial Diagnostic Approach

Confirm True Elevation

• Repeat the LDH measurement if the blood sample appears hemolyzed, because in-vitro hemolysis can falsely raise LDH values. 1 This is the single most common cause of spurious LDH elevation and must be excluded first. 2

Assess Degree of Elevation

• **Mild elevation (<5× upper limit normal) is most commonly associated with benign causes**, while severe elevation (>10× normal) carries a high mortality rate exceeding 50%. 1, 3
• Elevations 2-3× normal occur in 45% of cases, 3-10× normal in 47.5%, and >10× normal in only 7.5% of cases. 3

Systematic Evaluation by LDH Level

For Any Degree of Elevation: Rule Out Hemolysis First

The combination of elevated LDH and decreased haptoglobin is specific for hemolysis, as LDH alone can be elevated in liver disease, myocardial infarction, kidney disease, and muscle damage. 2

Order the following tests immediately:

• Haptoglobin (decreased in hemolysis) 2
• Indirect bilirubin (elevated in hemolysis) 2
• Reticulocyte count (elevated in active hemolysis) 2
• Direct Coombs test (positive in immune-mediated hemolysis) 2
• Peripheral blood smear (to identify spherocytes, schistocytes, or other abnormal morphologies) 2

Review medication history for hemolysis-inducing agents including daptomycin, cephalosporins, penicillins, NSAIDs, quinidine, and rifampin. 2

For Mild-Moderate Elevation (1.5-5× ULN): Assess Hepatic Function

Assess hepatic function when LDH is mildly elevated (≈1.5 × ULN) by ordering ALT, AST, alkaline phosphatase, and total bilirubin to identify hepatitis, cirrhosis, or biliary obstruction. 1 Isolated elevated alkaline phosphatase of hepatic origin that persists over time suggests chronic cholestatic processes. 4

For Moderate-Severe Elevation (>1.5× ULN): Screen for Malignancy

In a 31-year-old woman with unexplained LDH >1.5 × ULN, specific malignancy screening is warranted:

• Very high isolated LDH (≥800 IU/ml) is a distinguishing biomarker for cancer (27% vs. 4% in controls), liver metastases (14% vs. 3%), hematologic malignancies (5% vs. 0%), and infection (57% vs. 28%). 5

• Elevated LDH was the early and only sign of occult malignant lymphoma in asymptomatic patients, appearing 2 months before clinical manifestations. 6 A patient with no apparent cause for elevated serum LDH warrants thorough work-up including abdominal CT scan. 6

• Do not rely on LDH alone to diagnose cancer; combine LDH with disease-specific markers to improve specificity. 1 However, in a young woman, germ cell tumors are less likely than in males.

For Severe Elevation (>10× ULN): Urgent Evaluation Required

LDH elevation higher than 10-fold the normal rate is a pejorative predictive criterion, with hospitalization in intensive care in 73% of cases and mortality rate of 53%. 3 This level of elevation occurs in both benign (11 cases) and malignant (4 cases) diseases and does not differentiate between them. 3

Urgent evaluation should include:

• Assessment for tumor lysis syndrome risk, particularly if any hematologic malignancy is suspected 1
• Measurement of serum uric acid 1
• Complete blood count with differential 1
• Comprehensive metabolic panel 1

Age and Gender-Specific Considerations

Pregnancy-Related Causes

• Preeclampsia can cause elevated LDH and must be considered in any woman of childbearing age. 1 Check blood pressure, urinalysis for proteinuria, and platelet count.

Physiologic Causes

• Strenuous exercise can temporarily elevate LDH levels due to muscle damage. 1 Obtain detailed exercise history from the preceding 24-48 hours.
• Levels are physiologically higher in childhood associated with bone growth. 4

Common Pitfalls to Avoid

• Never interpret LDH in isolation; it must be assessed together with disease-specific markers such as haptoglobin for hemolysis, liver enzymes for hepatic disease, and tumor markers for malignancy. 1
• The degree of LDH elevation does not reliably differentiate benign from malignant causes (average values: 2708 vs 2842 UI/L). 3
• Haptoglobin can be decreased in patients with mechanical heart valves without clinically relevant hemolysis, and schizocytes may be absent in early thrombotic microangiopathy. 2
• In-vitro hemolysis is the most common cause of spurious elevation and must always be excluded first. 1, 2

Algorithmic Summary

1. Repeat test if sample hemolyzed 1
2. Check haptoglobin, indirect bilirubin, reticulocyte count, Coombs test, peripheral smear 2
3. If hemolysis confirmed: Review medications, assess for hereditary disorders 2
4. If no hemolysis: Order ALT, AST, alkaline phosphatase, bilirubin 1
5. If LDH ≥800 IU/ml or persistent elevation: Obtain abdominal CT scan to evaluate for occult malignancy, particularly lymphoma or liver metastases 6, 5
6. If LDH >10× ULN: Urgent hospitalization and intensive monitoring 3
7. Consider pregnancy testing and blood pressure measurement in all women of childbearing age 1