Endocrine Abstracts

Introduction: Differentiation between Cushing’s disease (CD) and ectopic Cushing’s syndrome (ECS) remains a diagnostic challenge. Currently available tests lack sufficient sensitivity and specificity or are invasive and technically difficult. Recently, an ACTH-UFC index has been proposed to differentiate the two forms of ACTH dependent Cushing’s syndrome (CS) (Ding, 2021). This work aimed to confirm the diagnostic utility of the ACTH-UFC index to differentiate CD from ECS.

Methods: Retrospective analysis of patients with ACTH-dependent CS seen at the Endocrinology Departments of Puerta de Hierro and Ramón y Cajal Hospitals between 1983 and 2021. The tests’ diagnostic performance was evaluated by ROC curves. Gold standard for CD or ECS diagnosis was based on positive staining for ACTH in a tumor sample, remission of CS after tumor excision or inferior petrosal sinus sampling.

Results: 80 patients were included (56 female, median age 43 years). 66 were diagnosed with CD (82.5%) and 14 with ECS (17.5%). Median plasma cortisol was 24 μg/dl at 0800 h, 21 μg/dl at 23 h, and 16 μg/dl after suppression with 1 mg dexamethasone, with no significant difference between both groups. Median UFC was 250 μg/day (887 μg/day in the ECS group Vs 221 μg/day in the CD group; P<0.001) and median plasma ACTH was 50 pg/ml (88 pg/ml Vs 48 pg/ml; P=0.014). The area under the ROC curve (AUC) for the ACTH-UFC index in predicting CD among ACTH-dependent CS was 0.852, lower than the 0.977 in the original study. The optimal cut-off value for the ACTH-UFC index was 1.0 (sensitivity of 68% and specificity of 93% to identify CD). In multivariate analysis, UFC showed an independent association with the diagnosis, with values >250 μg/day increasing the probability of ECS by 16.2 times (P=0.01). ACTH levels did not show this association. Accordingly AUC from isolated UFC was similar to that of the ACTH-UFC index (0.828). The exclusion from the analysis of cases with clinical evidence of ECS nullified the diagnostic utility of the ACTH-UFC index (AUC=0.652) and the isolated UFC (AUC=0.567). Nevertheless, diagnosing CD with an ACTH-UFC index ≤1 and ECS with an index ≧28, could save 63% of cases from additional testing, with a 98% certainty of correctly diagnosis.

Conclusions: ACTH-UFC index showed a worse diagnostic performance than referred and not superior to isolated UFC. In cases with greater diagnostic difficulty, neither of these tests were useful. However ACTH-UFC index could save more than 60% of cases from additional testing.