CushieBlog

Purpose

Bilateral inferior petrosal sinus sampling (BIPSS) is considered the most accurate procedure to confirm the diagnosis of Cushing’s disease (CD). However, it is a cumbersome and costly procedure. We aim to determine whether the corticotropin-releasing hormone (CRH) test alone might differentiate CD from ectopic adrenocorticotropin (ACTH) syndrome (EAS).

Methods

In this retrospective, observational study we investigated 523 consecutive patients with ACTH-dependent hypercortisolism: 502 with CD and 21 with EAS. All patients underwent a CRH test and surgery for the removal of the ACTH-secreting tumor. Two hundred patients with CD and 17 with EAS underwent BIPSS. The diagnostic CRH test performance included sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR).

Results

using a 50% ACTH increase as the threshold, the CRH test correctly classified 438 cases of CD (87%) and 20 cases of EAS (95%). The diagnostic metrics were as follows: SE 87%, SP 95%, PPV 99%, NPV 23%, accuracy 92%, PLR 18.35, and NLR 0.05. BIPSS correctly diagnosed all cases of EAS (100%) and 188 cases of CD (94%).

Conclusions

Our study shows that a positive CRH test reliably differentiates CD from EAS and obviates the need for BIPSS. The performance of CRH test is similar in patients with and without a visible pituitary microadenoma or a microadenoma < 6 mm. Accepting the very low probability of EAS in a patient with positive ACTH response to CRH, we can propose pituitary surgery without performing BIPSS.