Diagnostic performance of adenosine deaminase activity in pleural fluid: a single-center experience with over 2100 consecutive patients

Eur J Intern Med. 2010 Oct;21(5):419-23. doi: 10.1016/j.ejim.2010.03.011. Epub 2010 May 1.


Objective: To determine the diagnostic utility of adenosine deaminase (ADA) in a large series of pleural effusions of different etiologies.

Methods: A retrospective study of 2104 consecutive patients presenting with pleural effusion was carried out at a Spanish university hospital. ADA levels in pleural fluid were determined using a non-Giusti automatic kinetic assay, and a receiver operating characteristics curve analysis was applied to estimate their discriminative properties.

Results: Pleural tuberculosis (TB) accounted for 221 (10.5%) effusions. Pleural fluid ADA >35U/L yielded 93% sensitivity, 90% specificity, a positive likelihood ratio (LR) of 10.05 and a negative LR of 0.07 for the diagnosis of TB among lymphocytic exudates. The ADA activity was significantly higher in neutrophil- (111.6U/L) than in lymphocyte-rich (62.4U/L; p=0.002) TB effusions. Overall, more than 40% of parapneumonics and half of lymphomatous effusions exceeded the cutoff set for TB. These were the only causes of ADA activity above 250U/L. When the prevalence of TB as a cause of exudative effusions is low (e.g., 1%), the estimated positive predictive value of the ADA test may be as low as 7%, although the negative predictive value remains high (99.9%).

Conclusion: Where available, pleural ADA should be routinely used to rule TB in or out in areas with moderate to high or low TB prevalence, respectively. A high ADA level is a characteristic not only of lymphocytic, but also of neutrophilic TB effusions. An extremely high ADA activity should raise suspicion of empyema or lymphoma.

MeSH terms

  • Adenosine Deaminase / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism*
  • Empyema / diagnosis
  • Empyema / epidemiology
  • Empyema / metabolism
  • Enzyme Activation / physiology
  • False Positive Reactions
  • Humans
  • Lymphoma / diagnosis
  • Lymphoma / epidemiology
  • Lymphoma / metabolism
  • Middle Aged
  • Pleural Effusion, Malignant / diagnosis*
  • Pleural Effusion, Malignant / epidemiology
  • Pleural Effusion, Malignant / metabolism*
  • Predictive Value of Tests
  • Prevalence
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tuberculosis, Pleural / diagnosis*
  • Tuberculosis, Pleural / epidemiology
  • Tuberculosis, Pleural / metabolism*
  • Young Adult


  • Biomarkers
  • ADA protein, human
  • Adenosine Deaminase