Normal Values of Adenosine Deaminase
There is no single "normal" reference range for adenosine deaminase (ADA) because the test is measured in different body fluids with different diagnostic thresholds, and serum ADA should not be used for tuberculosis diagnosis. 1, 2
Serum ADA Reference Ranges
- Serum ADA1: Upper limit 7.2 U/L 3
- Serum ADA2: Upper limit 14.6 U/L 3
- Total serum ADA in healthy donors: Mean 16.5 ± 3.18 U/L 4
Critical Caveat About Serum ADA
Never rely on serum ADA for tuberculosis diagnosis—it lacks specificity and is elevated in hepatitis, infectious mononucleosis, pneumonia, rheumatoid arthritis, empyema, and malignancy. 2 The British Thoracic Society and American College of Chest Physicians explicitly recommend measuring ADA in the appropriate body fluid (pleural, pericardial, peritoneal, or CSF) rather than serum. 2
Body Fluid ADA Diagnostic Thresholds
These are not "normal values" but rather diagnostic cutoffs to distinguish tuberculous from non-tuberculous disease:
Pleural Fluid
- Diagnostic threshold: 40 U/L 1
- Sensitivity: 76-90%, Specificity: 77-100% for tuberculous pleurisy 2
- Alternative threshold of 30 U/L yields 94% sensitivity and 95% specificity 5
- Values below 40 U/L generally exclude tuberculosis 1
Cerebrospinal Fluid (CSF)
- Diagnostic threshold: 9-10 U/L 6, 1
- Sensitivity: 79%, Specificity: 91% at this threshold 6, 1
- Values <4 U/L: Exclude tuberculosis with >93% sensitivity but <80% specificity 6, 1
- Values >8 U/L: Strongly suggest tuberculosis with >96% specificity but <59% sensitivity 6, 1
Peritoneal (Ascitic) Fluid
- Diagnostic threshold: 32-40 U/L in patients without cirrhosis 1
- Sensitivity: 100%, Specificity: 96.6-100% 1
- Lower threshold of 27-32 U/L in patients with cirrhosis 1
- Sensitivity: 91.7-100%, Specificity: 92-93.3% in cirrhotic patients 1
Pericardial Fluid
Critical Clinical Pitfalls
ADA Does Not Provide Definitive Diagnosis
ADA levels provide only supportive evidence and must be interpreted within the complete clinical context—they cannot definitively diagnose tuberculosis. 6, 1
False Positives
Empyema can elevate ADA above tuberculous thresholds (>40-47 U/L), creating a critical diagnostic pitfall. 7 To distinguish empyema from tuberculous pleurisy:
- Perform bench centrifugation: empyema leaves clear supernatant, tuberculous effusions remain milky 7
- Check pleural fluid glucose: empyema has significantly lower glucose (47.3 ± 25.3 mg/dL) versus non-infectious effusions (102.5 ± 35.6 mg/dL) 7
- Examine neutrophil predominance: bacterial effusions show 69 ± 23% neutrophils, while tuberculous effusions show lymphocyte predominance 7
- Send cultures for both bacteria AND tuberculosis simultaneously 7
HIV and Immunocompromised Patients
In HIV-infected patients, ADA concentrations may remain low even when tuberculosis is present, reducing test reliability. 2 However, one study found ADA remains sensitive (94%) even in patients with CD4 counts <50 cells/μL, with no correlation between ADA values and CD4 counts. 5
ADA Isoenzyme Analysis
High total ADA in tuberculous effusions is due mainly to ADA-2 (originating from monocytes/macrophages), not ADA-1. 8 Using combined criteria (ADA >47 U/L, ADA-2 >40 U/L, and 2'-deoxyadenosine deaminase/ADA ratio <0.49) achieves 100% sensitivity and 97% specificity for tuberculous pleurisy. 8