Clinical Significance of Lactate Dehydrogenase (LDH)
LDH is a nonspecific marker of tissue damage and cellular turnover that serves critical roles in cancer prognostication, particularly for testicular germ cell tumors and osteosarcoma, while also aiding in the diagnosis of pleural effusions and indicating severe underlying disease when markedly elevated.
Diagnostic Applications
Cancer Detection and Monitoring
In testicular germ cell tumors, LDH is a mandatory tumor marker that must be measured post-orchiectomy and immediately before chemotherapy for risk stratification using the International Germ Cell Cancer Collaborative Group (IGCCCG) classification 1.
For seminomas, LDH levels determine prognostic groups: good prognosis requires LDH <2.5× upper limit of normal (ULN), while LDH >2.5× ULN defines a separate prognostic category with 3-year progression-free survival of 75-80% versus 92-93% for the good-prognosis group 1.
In non-seminomatous germ cell tumors, LDH >1.5× ULN indicates intermediate prognosis, and LDH >10× ULN defines poor prognosis with 5-year overall survival of only 67% 1.
Osteosarcoma patients with elevated LDH have significantly worse outcomes, with 5-year disease-free survival of 39.5% versus 60% for those with normal values, and elevated LDH correlates with metastatic disease at presentation 1, 2.
Very high isolated LDH (≥800 IU/mL) is a distinguishing biomarker for metastatic cancer (27% of cases), liver metastases (14%), and hematologic malignancies (5%), warranting thorough investigation for severe underlying disease 3.
Pleural Effusion Diagnosis
LDH is a key component of Light's criteria for distinguishing exudative from transudative pleural effusions 2.
Pleural fluid is exudative if: pleural fluid LDH/serum LDH ratio >0.6, OR pleural fluid LDH >2/3 the ULN for serum LDH 2.
Multiple Myeloma Assessment
LDH should be measured at initial diagnostic workup for multiple myeloma as it helps assess tumor cell burden alongside beta-2 microglobulin 1.
In plasma cell leukemia, elevated LDH reflects high tumor burden and aggressive clinical presentation 2.
Prognostic Significance
Cancer Risk Stratification
In cancer of unknown primary (CUP), a two-factor prognostic score combines ECOG performance status with LDH: good prognosis requires ECOG 0-1 AND normal LDH, while poor prognosis is defined by ECOG >1 OR elevated LDH 1.
Elevated LDH is an independent predictor of mortality in admitted medical patients with very high levels (≥800 IU/mL), associated with 26.6% in-hospital mortality versus 4.3% in controls 3.
In AL amyloidosis, elevated LDH above ULN is an independent adverse prognostic marker for overall survival and 6-month mortality, specifically in patients not eligible for stem cell transplantation 4.
Important Caveats in Testicular Cancer
Do NOT use post-orchiectomy LDH to stage or predict prognosis in seminoma patients with involved nodes or metastatic disease 1.
Do NOT use LDH concentrations alone to guide treatment decisions for pure seminoma, as conclusive evidence is lacking that selecting therapy based on tumor marker levels yields better outcomes 1.
Measure LDH when treatment concludes, as rising tumor markers soon after therapy usually indicate progressive disease requiring salvage therapy 1.
Interpretation Considerations
Non-Malignant Causes
Numerous benign conditions elevate LDH, including liver disease, hemolysis, myocardial infarction, kidney disease, infections, and strenuous exercise 2.
Hemolysis of blood samples can falsely elevate LDH levels, requiring careful specimen handling 2.
In chronic hemolytic anemias, LDH levels around 500 units are common due to ongoing red blood cell destruction and should be interpreted alongside reticulocyte count, haptoglobin, and indirect bilirubin 5.
Clinical Context Dependency
The diagnostic value of LDH depends entirely on clinical context and must be interpreted alongside other clinical and laboratory findings 2.
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 is recommended 2.
In renal cell carcinoma follow-up, routine LDH measurements lack demonstrated benefit for detecting metastasis in clinically localized disease, though LDH has prognostic value in advanced disease 1.
Practical Clinical Algorithm
When encountering elevated LDH:
Verify specimen integrity to exclude hemolysis artifact 2.
If LDH ≥800 IU/mL, investigate aggressively for metastatic cancer, hematologic malignancies, or severe infection 3.
In known cancer patients, use LDH for prognostic stratification per disease-specific guidelines (testicular cancer, osteosarcoma, CUP) 1.
In pleural effusion, apply Light's criteria using LDH alongside protein measurements 2.
In unexplained elevation, assess for hemolysis markers, liver function, cardiac injury, and tissue breakdown 2, 5.