Twenty-five studies were included in the review (n=8,631). Study quality was generally good. All but one of the studies enrolled an appropriate spectrum of patients and all but one clearly reported the selection criteria. Verification bias was a potential problem in nine studies.
Urinary free cortisol (14 studies): The summary positive likelihood ratio was 10.6 (95% CI 5.5 to 20.5) and summary negative likelihood ratio was 0.16 (95% CI 0.08 to 0.33). There was moderate heterogeneity in the diagnostic odds ratio (I2=44%) and values for the likelihood ratio were not reported.
Midnight serum cortisol (six studies): The summary positive likelihood ratio was 9.5 (95% CI 1.7 to 54.1) and summary negative likelihood ratio was 0.09 (95% CI 0.03 to 0.28). There was considerable heterogeneity in the diagnostic odds ratio (I2=78%). In studies in which thresholds were assay driven, the test had poorer performance (two studies) than those in which thresholds were outcome driven (four studies): positive likelihood ratio 1.8 compared with 26.6 and negative likelihood ratio 0.47 compared with 0.05.
Midnight salivary cortisol (four studies): The summary positive likelihood ratio was 8.8 (95% CI 3.5 to 21.8) and summary negative likelihood ratio was 0.07 (95% CI 0.00 to 1.20). There was moderate heterogeneity in the diagnostic odds ratio (I2=50%).
1mg overnight DST (14 studies): The summary positive likelihood ratio was 11.6 (95% CI 5.8 to 23.1) and summary negative likelihood ratio was 0.09 (95% CI 0.05 to 0.14). There was little heterogeneity in the diagnostic odds ratio (I2=11%). Studies in which the prevalence of Cushing's syndrome was under 50% showed better performance (11 studies) than those in which the prevalence was over 50% (three studies): positive likelihood ratio 16.4 compared with 2.8 and negative likelihood ratio 0.06 compared with 0.11.
Two-day 2mg DST (eight studies): The summary positive likelihood ratio was 7.3 (95% CI 3.6 to 15.2) and summary negative likelihood ratio was 0.18 (95% CI 0.06 to 0.52). There was no heterogeneity in the diagnostic odds ratio (I2=0%).
Urinary free cortisol plus 1mg overnight DST (three studies): The summary positive likelihood ratio was 15.4 (95% CI 0.7 to 358.0) and summary negative likelihood ratio was 0.11 (95% CI 0.01 to 1.57). There was considerable heterogeneity in the diagnostic odds ratio (I2=90%).
All subgroups analyses, with the exception of those detailed above, failed to show significant associations.