Causes of Low Lactate Dehydrogenase (LDH) Levels
Low LDH levels are uncommon and generally not considered clinically significant, but can occur in liver disease, hypothyroidism, and certain genetic disorders affecting LDH synthesis.
Understanding LDH and Its Normal Function
Lactate dehydrogenase (LDH) is an intracellular enzyme present in nearly all body tissues that catalyzes the conversion of lactate to pyruvate. It exists as five different isoenzymes (LDH1-LDH5), each predominantly found in different tissues:
- LDH1 & LDH2: Heart, red blood cells, kidneys
- LDH3: Lungs, lymphatic tissue
- LDH4: Placenta, kidneys
- LDH5: Liver, skeletal muscle
Normal serum LDH levels typically range from 140-280 IU/L, though reference ranges may vary between laboratories.
Primary Causes of Low LDH Levels
1. Liver Diseases
- Chronic liver disease/cirrhosis: The liver is the only organ for LDH biosynthesis, so advanced liver disease can result in decreased LDH production 1
- Cholestatic liver disease: Patients with cholestasis may have transiently decreased LDH levels 1
2. Endocrine Disorders
- Hyperthyroidism: Patients with hyperthyroidism can have lower LDH concentrations compared to euthyroid controls 1
- Hypothyroidism (less common): Some cases may present with low LDH
3. Genetic Factors
- Hereditary LDH deficiency: Rare genetic disorders affecting LDH synthesis
- Congenital absence of LDH isoenzymes: Extremely rare condition
4. Medication Effects
- Certain drugs: Some medications may interfere with LDH production, particularly liver-toxic substances 1
- Anabolic steroids: Can reduce LDH levels by up to 40% 1
5. Laboratory Considerations
- Hemolysis during sample collection: Can falsely lower measured LDH levels
- Prolonged sample storage: LDH activity may decrease if samples are not processed promptly
- Laboratory error: Calibration issues or technical problems
Clinical Significance and Evaluation
Low LDH levels are generally not considered clinically significant and are rarely the focus of diagnostic workup. In contrast, elevated LDH is commonly used as a marker for tissue damage, hemolysis, and malignancy 2.
When low LDH is observed:
- Verify the result: Consider repeating the test to rule out laboratory error
- Review medications: Check for drugs that might affect LDH levels
- Evaluate liver function: Since the liver is the primary site of LDH synthesis, assess liver function with comprehensive liver tests
- Consider thyroid function: Thyroid disorders can influence LDH levels 1
Comparison with High LDH
While low LDH is uncommon and generally not concerning, elevated LDH is clinically significant and associated with:
- Tissue damage or necrosis
- Hemolysis
- Malignancies (particularly hematologic and metastatic disease) 3
- Infections
- Myocardial infarction
Very high isolated LDH (≥800 IU/L) is associated with higher mortality and is a distinguishing biomarker for cancer, liver metastases, hematologic malignancies, and severe infections 3.
Conclusion
Low LDH levels are relatively uncommon and generally not considered clinically significant. When observed, they may be associated with liver disease, certain medications, or rare genetic disorders. The clinical focus is typically on elevated LDH levels, which are more commonly associated with pathological conditions requiring further investigation.