What are the implications of elevated Lactate Dehydrogenase (LDH)?

From the Guidelines

Elevated lactate dehydrogenase (LDH) is a nonspecific marker of tissue damage that requires further investigation to determine the underlying cause, and management should focus on treating the underlying condition rather than the LDH elevation itself. When LDH is elevated, a comprehensive workup should include a complete blood count, comprehensive metabolic panel, and evaluation of organ-specific markers based on clinical presentation. LDH is an enzyme found in nearly all body tissues, with highest concentrations in the heart, liver, muscles, kidneys, lungs, and red blood cells. Common causes of elevated LDH include hemolysis, myocardial infarction, liver disease, muscle damage, certain cancers (particularly lymphomas and leukemias), and pulmonary conditions like pneumonia or pulmonary embolism.

Key Considerations

• The pattern of LDH isoenzyme elevation can sometimes help pinpoint the source of tissue damage. For example, LDH-1 elevation suggests cardiac injury, while LDH-5 points to liver or skeletal muscle damage.
• Serial LDH measurements may be useful in monitoring disease progression or response to treatment, particularly in certain malignancies where LDH serves as a tumor marker, as seen in studies such as 1 which discusses the prognostic significance of LDH levels in osteosarcoma.
• Elevated LDH levels are associated with a worse prognosis in various conditions, including osteosarcoma, as reported by Bacci et al. in 1, and follicular lymphoma, as outlined in the 'Follicular Lymphoma-specific International Prognostic Index' (FLIPI) risk factors in 1.
• In the context of plasma cell leukemia, elevated LDH and β2-microglobulin serum levels are indicative of a high tumor burden and aggressive clinical presentation, as discussed in 1.
• The NCCN clinical practice guidelines in oncology for multiple myeloma also highlight the importance of assessing LDH levels as part of the initial diagnostic workup to evaluate tumor cell burden, as stated in 1.

From the Research

Elevated LDH: Clinical Implications

Elevated lactate dehydrogenase (LDH) levels have been associated with various clinical conditions, including malignant lymphoma, cancer, and idiopathic pulmonary arterial hypertension. The following points summarize the clinical implications of elevated LDH:

• Malignant Lymphoma: Elevated serum LDH levels can be an early marker of occult malignant lymphoma, as seen in a study published in 1984 2. In this study, three patients with elevated LDH levels were found to have malignant lymphoma, highlighting the importance of further diagnostic investigation in patients with unexplained elevated LDH levels.
• Cancer: Very high isolated LDH levels (> 800 IU/ml) can be a distinguishing biomarker for the presence of cancer, liver metastases, hematologic malignancies, and infection, as reported in a 2014 study 3. This study found that patients with very high isolated LDH levels had a higher mortality rate and more in-hospital complications compared to controls.
• Multiple Myeloma: Increased serum LDH levels are associated with features of advanced disease and poor survival in patients with multiple myeloma, as shown in a 2011 study 4. This study found that patients with increased LDH levels had a median overall survival of 21 months, compared to 54 months for patients with normal LDH levels.
• Immune Suppression: Elevated LDH levels can be a marker of immune suppression in cancer, as LDH-A alters the tumor microenvironment and promotes the growth of immune-suppressive cells, as discussed in a 2017 study 5.
• Idiopathic Pulmonary Arterial Hypertension: High levels of serum LDH correlate with the severity and mortality of idiopathic pulmonary arterial hypertension, as reported in a 2015 study 6. This study found that patients with elevated S-LDH levels (> 250 IU/l) had a significantly lower survival rate compared to those with lower S-LDH levels.

Key Findings

The studies highlight the importance of considering elevated LDH levels as a potential indicator of underlying clinical conditions, including:

• Malignant lymphoma
• Cancer
• Multiple myeloma
• Immune suppression
• Idiopathic pulmonary arterial hypertension

These findings suggest that elevated LDH levels warrant further diagnostic investigation and may be associated with poor prognosis and increased mortality in certain clinical conditions 2, 3, 4, 5, 6.