The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing's syndrome

Summary objective It has been reported previously that the paired interpretation of the corticotrophin‐releasing hormone (CRH) test and the 8‐mg dexamethasone suppression test (HDDST) could have higher diagnostic power than any single test in the differential diagnosis of ACTH‐dependent Cushing's syndrome. This finding has not been confirmed thereafter in large series. The aim of the present study has been to assess the operating characteristics of either the CRH test or the overnight HDDST and also to evaluate the potential utility of combining the interpretation of both tests in the differential diagnosis of ACTH‐dependent Cushing's syndrome. design and patients We have reviewed the medical records of 59 consecutive cases with ACTH‐dependent Cushing's syndrome: 49 patients with proven Cushing's disease (CD) and 10 patients with proven ectopic ACTH syndrome (EAS). Univariate curves of the receiver operating characteristics (ROC) have been performed to define the best cut‐off values, the sensitivity and the specificity for CRH and overnight HDDST. A comparison between the areas under the ROC curves has also been performed. results For the CRH test, the point on the ROC curve closest to 1 corresponded to a value of ACTH percentage increment of 50%[sensitivity 86% (72·6–94·8) and specificity 90% (55·5–98·3)]. The best threshold for cortisol percentage (30%) increment gave inferior results [sensitivity 61% (45·5–75·6) and specificity 70% (34·8–93·0)]. For the HDDST, the point on the ROC curve closest to 1 corresponded to a value of cortisol decrease from the baseline of 50%[sensitivity 77% (62·7–88·5), specificity 60% (26·4–87·6)]. The area under the ROC curve of the ACTH percentage increment after CRH was significantly greater than the area under the diagonal [0·9 (0·7–1·0), P= 0·0001]. Conversely, the area under the cortisol percentage decrement after dexamethasone was not different from that obtained by chance [0·7 (0·5–0·9), P= ns]. The area under the ROC curve of CRH is significantly greater than that of overnight HDDST (P = 0·03). A correct diagnosis has been achieved by the CRH test in 86·5% of cases and by the HDDST in 73% (P = 0·06). The combination of both tests has given a correct diagnosis in a significantly lower percentage of cases than the CRH test alone (69%, P= 0·04). The bilateral inferior petrosal sinus sampling (BIPSS) has been performed in 29 patients (24 CD, five EAS) who had negative imaging and/or discordant results of the noninvasive