EFFECTIVENESS VERSUS EFFICACY - THE LIMITED VALUE IN CLINICAL-PRACTICE OF HIGH-DOSE DEXAMETHASONE SUPPRESSION TESTING IN THE DIFFERENTIAL-DIAGNOSIS OF ADRENOCORTICOTROPIN-DEPENDENT CUSHINGS-SYNDROME

High dose dexamethasone suppression testing has been widely employed i n the differentiation between pituitary ACTH-dependent hypercortisolis m [Cushing's disease (CD)] and the ectopic ACTH syndrome. We hypothesi zed that the high dose dexamethasone suppression test as it is perform ed in practice does not improve the ability to differentiate between t hese two types of ACTH-dependent Cushing's syndrome. Cases were drawn from 112 consecutive patients with ACTH-dependent Cushing's syndrome, who were then classified based upon results of inferior petrosal sinus sampling for ACTH levels. Analysis of test characteristics of high do se dexamethasone suppression testing was performed in the 73 patients for whom results are available. Statistical modeling was performed usi ng the 68 cases with complete data on all assessed variables. Logistic regression models were used to predict the probability of pituitary-d ependent Cushing's syndrome (CD) given the results of high dose dexame thasone suppression testing before and after adjustment for the contri bution of a series of potential covariates. Of the 112 patients with A CTH-dependent Cushing's syndrome, 15.2% had the ectopic ACTH syndrome, and the remainder had pituitary-dependent Cushing's syndrome (CD). Pa tients with the ectopic ACTH syndrome were significantly older (mean, 51.9 vs. 40.2), were more likely to be male (58.8% vs. 27.4%), had sho rter duration of clinical findings (mean, 11.6 us. 39.9 months), were more likely to have hypokalemia (50% vs. 8.6%), had higher baseline 24 -h urinary free cortisol [mean, 8317 vs. 1164 nmol/day (3015 vs. 422 m u g)] and plasma ACTH levels [mean, 47 vs. 17 pmol/L (210 vs. 78 pg/mL )] and were less likely to suppress urinary free cortisol or plasma co rtisol with high dose dexamethasone using the standard criterion of 50 % or more suppression compared with patients with pituitary-dependent Cushing's syndrome. Based upon the standard criterion, the sensitivity and specificity of the high dose dexamethasone suppression test for t he diagnosis of pituitary-dependent Cushing's syndrome were 81.0% and 66.7%, respectively. Although the mean percent suppression was signifi cantly greater for patients with CD than for those with the ectopic AC TH syndrome (72.2% vs. 41.3%), the range of suppression was 0-99% for each diagnosis. The area under the receiver operating characteristic c urve was 0.710 (95% confidence interval, 0.541-0.879). Logistic regres sion models were used to evaluate the probability of CD given the resp onsiveness to high dose dexamethasone suppression testing before and a fter adjustment for the potential contributions of other factors. A mo del including all of the variables (age, sex, duration, presence of hy pokalemia, urinary free cortisol, and plasma ACTH) had a diagnostic ac curacy of 92.7%. A model including all of these variables plus a binar y variable indicating whether the patient met the criterion of suppres sion by 50% or more resulted in 95.6% accuracy, whereas substitution o f this binary variable by percent suppression resulted in a model with 94.1% accuracy. There were no statistically significant differences a mong these models; their values for the c statistic, which is equivale nt to the area under the curve in a receiver operating characteristic analysis, mere all greater than 0.9. Logistic regression models indica te that the results of the dexamethasone suppression test add little t o the differential diagnosis of ACTH-dependent Cushing's syndrome, esp ecially after taking other clinical information into account. In our p atient population, the sensitivity and specificity of the dexamethason e suppression test were less than those reported by others. However, b ecause 20-33% of cases of ectopic ACTH syndrome are misdiagnosed with these logistic regression models, other techniques are necessary to ac hieve greater diagnostic accuracy.