Enhancing Cushing’s disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS

Abstract

IntroductionThe differential diagnosis between Cushing’s disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available.ObjectiveThis retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS), applying different cutoff values.MethodsA total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy.ResultsUsing the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance.DiscussionACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing’s syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS.

ACTH-dependent Cushing Syndrome with No Peripheral Response But a Marked Petrosal Sinus ACTH Response to Desmopressin

“…This is an unusual case of highly positive petrosal sinus ACTH stimulation by desmopressin without any peripheral response, suggesting a central source of ACTH in a patient with ACTH-dependant CS. Three similar cases with a lack of peripheral ACTH response in the initial desmopressin test but with a central response during IPSS were reported; however, simultaneous peripheral ACTH results were not provided ( 4 ). According to a recent meta-analysis, the desmopressin stimulation test has a sensitivity of 88% for discriminating CD from normal patients with clinical or biochemical features suggestive of CS, indicating nonetheless a false-negative rate of 12% ( 5 ).…”

Subtyping of Cushing’s Syndrome: A Step Ahead

“…Desmopressin is an alternative to CRH during BIPSS [31], with the same procedure and diagnostic accuracy; however, it is less ex-pensive [32]. Nonetheless, desmopressin is a pro-coagulant agent; its use during BIPSS needs extreme caution given the increased risk of thromboembolic events in CS [33].…”

Does Desmopressin Impact Lateralization in Bilateral Inferior Petrosal Sinus Sampling?

“…Despite its invasive procedure, BIPSS remains the established gold standard for the precise localization of ACTH)-dependent CS [3,5,10,12,13]. Landolt notably enhanced the sensitivity of BIPSS by incorporating CRH stimulation (14).…”