Lactate dehydrogenase (LDH) test

ALSO KNOWN AS: Lactic acid dehydrogenase, L-lactate: NAD+ oxidoreductase, LD test, lactic dehydrogenase

DEFINITION: Lactate dehydrogenase (LDH) is a ubiquitous intracellular enzyme that catalyzes the interconversion of pyruvate and lactate. In oncology, it is a serum marker for cell damage or turnover. The enzyme is a tetramer of H (heart) and M (muscle) subunits, allowing five possible isoenzyme forms—LDH-1 (H4), LDH-2 (H3M1), LDH-3 (H2M2), LDH-4 (H1M3), and LDH-5 (M4).

Cancers diagnosed: Malignancies causing effusions, germ-cell tumors, and other tumors with high cell turnover, including melanoma, lymphoma, testicular cancer, and leukemia

Why performed: Serum LDH is elevated in many non-neoplastic diseases. In oncology, its concentration may estimate the stage of disease and prognosis in several cancers, such as non-Hodgkin lymphoma, myeloma, and metastatic prostate carcinoma. The ratio of serum LDH to LDH concentration in pleural, peritoneal, or pericardial effusions can help distinguish benign from malignant processes. High LDH concentrations in effusion fluid suggest the presence of cancer. Because the five isoenzymes have characteristic relative abundances in different tissues, a determination can assist in diagnosing several tumors. LDH tests are also used to monitor the progress of chemotherapy treatment.

Patient preparation: No fasting or other special preparation is necessary for this simple blood test.

Steps of the procedure: After the blood sample is collected, the serum is isolated by centrifugation, and the activity of the enzyme is measured in either the forward direction (oxidation of lactate and NAD+ to pyruvate, NADH, and H+) or the reverse direction. In the forward reaction, the rate of appearance of NADH can be followed spectrophotometrically because it strongly absorbs ultraviolet (UV) light at 340 nM; NAD+ does not. The enzyme activity is calculated by comparing the rate of NADH appearance in the patient sample to rates obtained from standard preparations. If the cause of elevated LDH cannot be determined by other means, the isoenzymes can be separated by electrophoresis, with LDH-1 (all H subunits) migrating fastest, followed in order by LDH-2 through LDH-5. LDH can also be visualized in tissue sections by immunohistochemistry.

After the procedure: No special aftercare is required other than monitoring the blood collection site for signs of infection until healed.

Risks: There are no risks to the patient. High false positive rates are seen in patients with other systemic illnesses.

Results: Abnormally high LDH values and abnormal isoenzyme patterns are seen in many diseases and must be interpreted considering clinical history and other laboratory results. Results for enzyme activity obtained with different methods are not interchangeable. In oncology, abrupt increases in LDH indicate an unfavorable prognosis in terminally ill patients, particularly those with melanoma. The LDH-1 isoenzyme is reliably elevated in germ-cell tumors (teratoma, seminoma, or ovarian dysgerminoma) and can serve as a tumor marker. In leukemia, lymphoma, and multiple myeloma, LDH-3 and LDH-4 are often elevated. Elevated LDH-5 in colorectal cancer is strongly associated with poor survival.

Bibliography

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Farhana, Aisha, and Sarah L. Lappin. "Biochemistry, Lactate Dehydrogenase." National Library of Medicine, 1 May 2023, www.ncbi.nlm.nih.gov/books/NBK557536. Accessed 20 June 2024.

Feng, Yangbo, et al. “Lactate Dehydrogenase A: A Key Player in Carcinogenesis and Potential Target in Cancer Therapy.” Cancer Medicine, vol. 7, no. 12, 2018, pp. 6124-6136. doi:10.1002/cam4.1820.

"Lactate Dehydrogenase Test." MedlinePlus, 30 Oct. 2023, medlineplus.gov/lab-tests/lactate-dehydrogenase-ldh-test. Accessed 20 June 2024.

"LDH Test." Cleveland Clinic, 15 Apr. 2024, my.clevelandclinic.org/health/diagnostics/22736-lactate-dehydrogenase-ldh-test. Accessed 20 June 2024.

Philipp, Alexander B., et al. "Circulating Cell-Free Methylated DNA and Lactate Dehydrogenase Release in Colorectal Cancer." BMC Cancer, vol. 14, no. 1, 2014, pp. 1–21. doi:10.1186/1471-2407-14-245.

Wu, Mei-ying, et al. "Clinical Evaluation of Potential Usefulness of Serum Lactate Dehydrogenase (LDH) in 2019 Novel Coronavirus (COVID-19) Pneumonia." Respiratory Research, vol. 21, 2020, pp. 1-6.

doi.org/10.1186/s12931-020-01427-8.