Low Serum LDH: Clinical Significance and Evaluation
Low serum lactate dehydrogenase (LDH) levels have minimal clinical significance and are rarely associated with pathological conditions; they do not require routine investigation in the absence of specific clinical concerns. 1, 2
Why Low LDH Is Clinically Unimportant
The medical literature and clinical guidelines focus almost exclusively on elevated LDH because this enzyme serves as a marker of tissue damage, cell turnover, and specific disease states. 3, 1 Low LDH values lack established diagnostic or prognostic utility across all major clinical domains—cardiology, hepatology, hematology, and oncology. 2
- LDH is released from damaged cells through compromised cell membranes, making elevated levels clinically meaningful as indicators of tissue injury, hemolysis, malignancy, or inflammation. 3, 4
- No disease states are characterized by pathologically low LDH, unlike elevated LDH which has well-defined associations with myocardial infarction, hemolytic anemia, lymphomas, testicular cancer, and numerous other conditions. 2
- Systematic reviews of LDH clinical applications identify no rational use for investigating low values, as they provide no diagnostic, monitoring, or prognostic information. 2
Technical Considerations
Low LDH measurements may occasionally reflect pre-analytical issues rather than true physiological states:
- Sample handling errors can theoretically reduce measured LDH activity, though this is far less common than the false elevation caused by in-vitro hemolysis. 3
- Laboratory reference ranges are established to capture normal physiological variation, and values at the lower end of normal simply represent individual biological variability without clinical consequence. 5
When to Ignore Low LDH
Do not pursue further workup for isolated low LDH values in asymptomatic patients, as no evidence supports clinical benefit from such investigations. 2
- If low LDH is discovered incidentally during routine testing, no additional laboratory tests, imaging, or specialist referrals are warranted based solely on this finding. 2
- Focus clinical attention on elevated LDH when present, as this has established diagnostic utility in differentiating transudative from exudative pleural effusions (Light's criteria), diagnosing hemolysis, and risk-stratifying malignancies. 6, 3, 7
Common Clinical Pitfall
The most important pitfall is over-interpreting or investigating low LDH values, which wastes healthcare resources and may cause unnecessary patient anxiety without providing actionable clinical information. 2 Clinicians should reserve LDH interpretation for elevated values where extensive evidence supports clinical decision-making. 3, 2