What causes false positive Angiotensin-Converting Enzyme (ACE) levels?

Causes of False Positive Angiotensin-Converting Enzyme (ACE) Levels

The most common causes of false positive ACE levels include sarcoidosis, HIV infection, granulomatous diseases, and cocaine use with levamisole adulteration. 1, 2, 3

Primary Causes of Elevated ACE Levels

• Granulomatous Diseases:

  • Sarcoidosis is the most well-established cause of elevated ACE levels, with 77-85% of patients with active sarcoidosis showing elevated levels 2, 4
  • Silicosis can cause ACE elevation (mean 646.5 ng/mL vs 453.7 ng/mL in controls) 5
  • Miliary tuberculosis (but not cavitary tuberculosis) shows elevated ACE levels (mean 647.0 ng/mL) 5

• Infectious Diseases:

  • HIV infection significantly elevates ACE levels (55.4-57.2 U/L vs 31.9 U/L in controls) 3
  • Parasitic infections can lead to elevated p-ANCA with specificity to certain antigens, potentially affecting ACE levels 1

• Drug-Related Causes:

  • Cocaine use, particularly when adulterated with levamisole, can cause ANCA-positive vasculitis and affect ACE levels 1
  • Certain medications may interfere with ACE measurement by affecting enzyme activity 5

• Other Medical Conditions:

  • Inflammatory bowel disease can be associated with p-ANCA positivity 1
  • Rheumatoid arthritis may show elevated ACE levels 1
  • Autoimmune liver disease can present with abnormal ACE levels 1

Physiological Factors Affecting ACE Levels

• Age and Gender Variations:

  • ACE activity is greater in male subjects than in females of comparable age 2
  • Children have higher ACE levels than adults 2
  • Increasing age can affect baseline ACE levels 6

• Smoking Status:

  • History of smoking can influence ACE levels and is a risk factor for ACE-inhibitor induced angioedema 6

Laboratory and Technical Considerations

• Assay Variations:

  • Different methods for measuring ACE (activity vs. concentration) may yield different results 5
  • Immunoassays measuring ACE concentration avoid problems with inhibitors but may have different reference ranges 5

• Endogenous Inhibitors:

  • Presence of endogenous ACE inhibitors can affect activity measurements but not concentration measurements 5
  • COPD patients show elevation of ACE specific activity, suggesting release of different ACE isozymes with higher specific activity 5

Clinical Implications

• Diagnostic Value:

  • Serum ACE has a very high negative predictive value (97% in adults, 96.9% in children) for sarcoidosis, making it useful for ruling out the disease 4
  • Positive predictive value is much lower (43.6% in adults, 10% in children), indicating that elevated levels require further confirmation 4

• Monitoring Considerations:

  • ACE levels in sarcoidosis patients receiving corticosteroids typically normalize, making it useful for monitoring treatment response 2
  • Patients with resolved sarcoidosis generally show normal ACE levels 2

Important Caveats

• Reduced ACE Levels:

  • Chronic obstructive lung disease, lung cancer, tuberculosis, and cystic fibrosis can actually reduce serum ACE levels compared to controls 2
  • Corticosteroid therapy significantly reduces ACE levels 2

• ACE Inhibitor Therapy:

  • Patients taking ACE inhibitors will have falsely low ACE activity levels, though ACE concentration may still be measurable 5
  • ACE inhibitors can cause cough in 5-10% of white patients and up to 50% in Chinese patients, which could confound respiratory symptom evaluation 1

Understanding these various causes of false positive ACE levels is crucial for accurate interpretation of test results and appropriate clinical decision-making.