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Lactate Dehydrogenase (LDH)

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A Quick Guide for Patients: Understanding LDH

  • What is Lactate Dehydrogenase (LDH)? Lactate Dehydrogenase (LDH) is an enzyme found inside almost every cell in your body. When cells are damaged or destroyed, they release LDH into the bloodstream.
  • A General Alarm Bell: A high LDH level is a non-specific "alarm bell" that signals tissue injury somewhere in the body. It does not point to a specific disease on its own.
  • Many Possible Causes: An elevated LDH can be caused by many conditions, ranging from strenuous exercise and minor injuries to more serious issues like heart, liver, or blood disorders, infections, and cancer.
  • Role in Cancer Care: In oncology, LDH is used as a non-specific tumor marker. It can help estimate the amount of cancer (tumor burden) and provide prognostic information. It is particularly useful for monitoring lymphomas and testicular cancer.
  • Context is Key: Your doctor will always interpret your LDH result in the context of your symptoms, a physical exam, and other, more specific, lab tests and imaging studies.

Lactate Dehydrogenase (LDH) Overview

Lactate dehydrogenase (LDH) is an enzyme found in nearly all body tissues, catalyzing the reversible conversion of lactate to pyruvate in the final step of glycolysis. It plays a crucial role in energy production, particularly under anaerobic conditions. LDH is released into the bloodstream when cells are damaged or destroyed, making its serum levels a non-specific marker of tissue injury.

LDH measurement in blood is used clinically to detect and monitor conditions involving cell damage, including cancers, hemolysis, heart attacks, liver diseases, and infections. It is not diagnostic on its own but provides supportive evidence when combined with other tests.

Tumour markers serve as indispensable tools in the realm of cancer detection and diagnosis, offering valuable insights into disease progression and treatment response.

Indications for LDH Testing

LDH testing is indicated in various clinical scenarios:

  1. Tumor Marker Evaluation:
    • Monitoring disease progression, treatment response, and recurrence in lymphomas, germ cell tumors, and other malignancies.
    • Part of prognostic scoring systems (e.g., International Prognostic Index for lymphomas).
  2. Hemolysis Detection: To confirm intravascular hemolysis in hemolytic anemias, where LDH elevation accompanies reduced haptoglobin and elevated bilirubin.
  3. Myocardial Infarction: Historically used (now largely replaced by troponins) to detect heart muscle damage.
  4. Liver and Muscle Injury: Assessing damage in hepatitis, cirrhosis, muscular dystrophies, or rhabdomyolysis.
  5. Infections and Inflammation: Elevated in severe infections like sepsis or meningitis.

LDH Biology and Isoenzymes

LDH is a tetrameric enzyme composed of H (heart) and M (muscle) subunits, forming five isoenzymes (LDH-1 to LDH-5) separable by electrophoresis:

  • LDH-1 (HHHH): Predominant in heart and red blood cells.
  • LDH-2 (HHHM): Abundant in white blood cells and kidney.
  • LDH-3 (HHMM): Found in lungs and platelets.
  • LDH-4 (HMMM): Present in liver and skeletal muscle.
  • LDH-5 (MMMM): Highest in liver and skeletal muscle.

Isoenzyme analysis helps localize the source of elevation (e.g., LDH-1 flip in myocardial infarction). LDH requires NAD+ as a cofactor and is inhibited by high lactate levels.

LDH as a Tumor Marker

Elevated LDH is a non-specific tumor marker reflecting tumor burden and cell turnover:

  • Lymphomas: High LDH in non-Hodgkin and Hodgkin lymphomas correlates with aggressive disease and poor prognosis.
  • Germ Cell Tumors: Markedly elevated in seminomas and non-seminomas; used for staging, monitoring chemotherapy, and detecting relapse.
  • Other Cancers: Seen in melanoma, neuroblastoma, Ewing sarcoma, and leukemias. Part of lactate-driven Warburg effect in cancer metabolism.

Declining LDH post-treatment indicates response; rising levels suggest progression.

LDH in Hemolysis and Anemia

LDH is highly concentrated in erythrocytes, making it a sensitive marker for hemolysis:

  • Intravascular Hemolysis: Causes dramatic LDH elevation (often >1000 U/L), with LDH-1 and LDH-2 predominant.
  • Conditions: Autoimmune hemolytic anemia, sickle cell crisis, thrombotic thrombocytopenic purpura (TTP), or mechanical hemolysis (e.g., prosthetic valves).

Combined with low haptoglobin, schistocytes on smear, and reticulocytosis for diagnosis.

LDH in Heart and Liver Diseases

Cardiac: LDH-1 elevation (with LDH-1 > LDH-2 "flip") in myocardial infarction, though troponins are preferred now.

Hepatic: LDH-5 predominant in acute hepatitis, cirrhosis, or liver metastases. Less specific than ALT/AST but useful in monitoring.

Also elevated in pulmonary embolism (LDH-3) and muscle disorders like dermatomyositis.

Interpreting LDH Levels

Normal serum LDH: 140-280 U/L (varies by lab and method). Interpretation considers:

  • Mild Elevation (1-2x normal): Non-specific; seen in inflammation, minor injury.
  • Moderate (2-10x): Hemolysis, infections, tissue necrosis.
  • Severe (>10x): Extensive cell death (e.g., tumor lysis syndrome, massive hemolysis).
  • Isoenzymes: Provide tissue specificity.

Always correlate with clinical context and other markers.

LDH in Other Conditions

LDH elevates in:

  • Megaloblastic anemias (ineffective erythropoiesis).
  • Renal infarction or rejection.
  • Hypoxia, shock, or sepsis.
  • Testicular torsion or trauma.

False elevations from hemolyzed samples (in vitro hemolysis). LDH in pleural/peritoneal fluids aids in distinguishing exudates (high LDH) from transudates.

Frequently Asked Questions (FAQ)

My LDH level is high. Should I be worried about cancer?

Not necessarily. While LDH is used as a tumor marker, it is extremely non-specific. An elevated LDH is much more likely to be caused by other common issues, such as strenuous exercise, a minor infection, anemia, or a problem with the blood sample itself (hemolysis). Your doctor will only consider cancer if other, more specific signs and symptoms are present.

Why is my blood sample for LDH sometimes rejected or needs to be redrawn?

This is usually due to "hemolysis." Red blood cells are packed with LDH. If the blood cells break during or after the blood draw (due to a difficult draw or rough handling), the LDH leaks out into the serum, causing a falsely high result that does not reflect what is actually happening in your body. To ensure an accurate reading, the lab may request a new, non-hemolyzed sample.

If LDH is so non-specific, why is it still used in cancer care?

In the context of a known cancer diagnosis (like lymphoma or testicular cancer), LDH becomes a very useful tool. It provides a simple, inexpensive way to estimate the overall "bulk" or activity of the tumor. Watching the LDH level fall during chemotherapy is a reassuring sign that the treatment is destroying cancer cells. Conversely, a rising level can be an early warning sign of disease progression or relapse.

Expert Interpretation is Key

An LDH level is never interpreted in isolation. It is a piece of a larger clinical puzzle. Always discuss your lab results with your healthcare provider to understand their significance in your specific situation.

Contact a Specialist for a Second Opinion

References

  1. National Cancer Institute (NCI). (n.d.). Tumor Markers. Retrieved from https://www.cancer.gov/about-cancer/diagnosis-staging/symptoms
  2. Mayo Clinic Laboratories. (n.d.). LD - Overview: Lactate Dehydrogenase (LDH), Serum. Retrieved from https://www.mayocliniclabs.com/test-catalog/Overview/8344
  3. American Society of Hematology (ASH). (2023). Hematology, ASH Education Program. Retrieved from https://ashpublications.org/hematology/issue/2023/1
  4. Oldenburg J, et al. (2022). Testicular seminoma and non-seminoma: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology, 33(4), 362-375. https://doi.org/10.1016/j.annonc.2022.02.007
  5. Drent M, et al. (1996). Usefulness of lactate dehydrogenase in pleural effusions. Chest, 110(4), 1033-1037. https://doi.org/10.1378/chest.110.4.1033
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