What is an LD (Lactate Dehydrogenase) Isoenzyme Panel?
An LD isoenzyme panel is a laboratory test that separates and measures the five distinct forms (isoenzymes) of lactate dehydrogenase enzyme in blood or body fluids, though routine determination of LDH isoenzymes is not recommended in clinical practice for most conditions. 1
Basic Biochemistry
Lactate dehydrogenase exists as a tetrameric protein composed of two types of subunits—M (muscle/A) and H (heart/B)—that combine to form five distinct isoenzymes designated LD1 through LD5. 2, 3
- LD1 (HHHH): Predominantly found in heart and red blood cells 3
- LD2 (HHHM): Found in heart and red blood cells 3
- LD3 (HHMM): Found in lungs and other tissues 3
- LD4 (HMMM): Found in liver, skeletal muscle, and kidney 3
- LD5 (MMMM): Predominantly found in liver and skeletal muscle 3
Clinical Measurement
The panel is performed using cellulose acetate electrophoresis followed by formazan staining to separate and visualize the five isoenzyme bands. 4 Total LDH activity is measured using the pyruvate to lactate reaction according to standardized methods. 2
Limited Clinical Utility
The European Germ Cell Cancer Consensus Group explicitly states that routine determination of LDH isoenzymes is not recommended, even in cancer diagnosis where total LDH has established prognostic value. 1
When Total LDH Alone is Sufficient:
- Testicular germ cell tumors: Total LDH is mandatory for advanced disease and serves as an important prognostic factor, but isoenzyme fractionation adds no clinical value 1
- Melanoma staging: Elevated total LDH is incorporated into AJCC stage IV classification as an independent predictor of poor outcome, without need for isoenzyme analysis 1, 5
- Multiple myeloma: Total LDH helps assess tumor burden in the Revised International Staging System 1, 5
- Pediatric acute lymphoblastic leukemia: Total LDH is part of the tumor lysis syndrome panel 1
Specific Scenarios Where Isoenzyme Patterns May Provide Information
Malignant vs. Non-Malignant Differentiation:
In serum, LD4 and LD5 isoenzymes are predominant in both malignant and non-malignant diseases, but serum LD5 is significantly higher than LD4 in malignant disease, while LD4 exceeds LD5 in non-malignant disease. 4
- Sensitivity for malignant ascites: LD5 activity 100%, LD4 activity 94%, LD1 activity 90% 6
- Specificity for malignant ascites: LD1 activity 70%, LD4 activity 62%, LD5 activity 56% 6
Ascitic Fluid Analysis:
In malignant ascites, LDH-4 and LDH-5 activities are significantly higher, while LDH-1 activity is lower compared to non-malignant ascites. 6
- Sterile cirrhotic ascites: LDH-1 activity is significantly higher than in spontaneous bacterial peritonitis, malignancy, tuberculosis, or heart failure 6
- Spontaneous bacterial peritonitis: LDH-2 and LDH-3 activities are elevated 6
Pleural Effusion Analysis:
LDH-4 and LDH-5 are the predominant isoenzymes in both pleural and ascitic fluids from malignant and non-malignant diseases, but the isoenzyme pattern does not reliably differentiate between specific types of malignancies. 4
- Empyema thoracis shows the highest pleural fluid total LDH activity 4
- Pleural fluid total LDH is useful for monitoring patients with chest tubes 4
Important Caveats
The serum LDH isoenzyme pattern is frequently modified by differing elimination rates of each isoenzyme and can be altered by LD-immunoglobulin complexes, genetic variants, or tumor-produced LD. 2
Isoenzyme patterns show great variation between species and cannot be extrapolated from one species to another, which is particularly important in veterinary medicine. 3
Hemolysis of blood samples can falsely elevate LDH levels, making proper specimen handling critical. 5
Normal Distribution Pattern
In healthy individuals, serum LD1 and LD2 isoenzymes are predominant, reflecting the normal contribution from cardiac and red blood cell turnover. 4 This baseline pattern shifts toward LD4 and LD5 predominance when tissue damage releases isoenzymes from liver, skeletal muscle, or malignant cells. 4, 3