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

From the Guidelines

Elevated lactate dehydrogenase (LDH) levels can result from almost any condition that causes cellular lysis or injury, including strenuous exercise, liver disease, myocardial infarction, kidney disease, hemolysis, pneumonia, and countless other conditions. The causes of elevated LDH are numerous and varied, reflecting the widespread distribution of LDH in body tissues. Common causes include:

• Myocardial infarction (heart attack), where damaged heart muscle releases LDH into the bloodstream
• Hemolytic anemia, where red blood cells break down prematurely
• Various malignancies such as lymphomas, leukemias, and solid tumors that have high cell turnover rates
• Liver diseases like hepatitis and cirrhosis
• Muscle damage from trauma, rhabdomyolysis, or muscular dystrophies
• Pulmonary conditions including pulmonary embolism and pneumonia
• Kidney diseases Certain medications can also cause LDH elevation, as can strenuous exercise 1. When evaluating elevated LDH, it's essential to consider it as a non-specific marker of tissue damage and correlate it with other clinical findings and more specific tests. LDH is an intracellular enzyme present in nearly all body tissues, particularly concentrated in the heart, liver, red blood cells, kidneys, muscles, brain, and lungs, which explains why damage to any of these tissues can result in increased serum LDH levels as the enzyme leaks from damaged cells into the bloodstream. In the context of osteosarcoma, elevated serum LDH level is also associated with a worse prognosis 2.

From the Research

Causes of Elevated Lactate Dehydrogenase (LDH)

Elevated LDH levels can be caused by various factors, including:

• Benign conditions, which account for 60% of cases 3
• Malignant conditions, which account for 36% of cases 3
• Undetermined conditions, which account for 5% of cases 3
• Cancer, particularly metastatic cancer and hematologic malignancies 4, 5
• Infections, such as sepsis and pneumonia 5
• Liver metastases 5
• Hematologic malignancies, such as leukemia and lymphoma 5
• Cardiac conditions, such as myocardial infarction 6
• Hepatic encephalopathy and lung fibrosis, which have high AUCs and sensitivities for elevated LDH activities 6
• Other conditions, such as gout and cerebral ischemia, which may have decreased LDH activities 6

Diagnostic and Prognostic Value of LDH

LDH has a diagnostic and prognostic value in various diseases, including:

• Cancer, where high LDH levels are associated with a poor prognosis 4
• Liver metastases, where high LDH levels are associated with a poor prognosis 5
• Hematologic malignancies, where high LDH levels are associated with a poor prognosis 5
• Infections, where high LDH levels are associated with a poor prognosis 5
• Hepatic encephalopathy and lung fibrosis, where LDH activities have high AUCs and sensitities 6

LDH Isoenzymes

LDH isoenzymes have different distributions in various tissues and can be used as biomarkers for specific diseases, including:

• Cardiac conditions, where the LDH1 isoenzyme is elevated 7
• Hepatic conditions, where the LDH5 isoenzyme is elevated 7
• Muscular conditions, where the LDH3 isoenzyme is elevated 7
• Other conditions, where different LDH isoenzymes may be elevated or decreased 7