The Application of the Combined Corticotropin-Releasing Hormone plus Desmopressin Stimulation during Petrosal Sinus Sampling Is Both Sensitive and Specific in Differentiating Patients with Cushing’s Disease from Patients with the Occult Ectopic Adrenocorticotropin Syndrome

Abstract

Context:Although bilateral inferior petrosal sinus sampling (BI-PSS) with CRH stimulation is the most accurate procedure for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), 4 -15% of patients with Cushing's disease (CD) fail to demonstrate diagnostic gradients. Preliminary data suggest that a more potent stimulation by the combined administration of CRH plus desmopressin during BIPSS may provide some diagnostic advantage. A crucial issue, however, is whether such an amplified stimulation may affect the specificity of the procedure, and this was the main aim of the present study. Objective:We investigated the diagnostic accuracy of BIPSS performed by CRH plus desmopressin stimulation. Design and Setting:A retrospective analysis was conducted at a single tertiary care center. Participants:Fifty-four patients were admitted for the investigation of ACTH-dependent CS. CD was diagnosed in 47 patients; occult ectopic ACTH syndrome (oEAS) was histologically confirmed in seven patients. Intervention(s):All patients underwent BIPSS with CRH plus desmopressin administration. Additional noninvasive tests included CRH test, high-dose dexamethasone suppression test, desmopressin test, and pituitary magnetic resonance imaging. Main Outcome Measures:Gradients of inferior petrosal sinus (IPS) to peripheral (IPS/P) ACTH were calculated before and after stimulation with CRH plus desmopressin. Results:The sensitivity for a basal IPS/P gradient greater than 2 was 61.7%, with 100% specificity and a diagnostic accuracy of 66.7%. After stimulation with CRH plus desmopressin, receiver operating characteristic (ROC) curve analysis showed that a cutoff gradient of more than 2 offers the best test performance. In total, 46 of 47 patients with CD had an IPS/P gradient greater than 2, but none of the patients with oEAS, resulting in a sensitivity of 97.9%. The specificity was 100%, diagnostic accuracy was 98.2%, and the positive and negative predictive values were 100 and 87.5%, respectively. A subgroup of 18 patients (16 with CD and two with oEAS) had contradictory responses to routine tests with CRH and/or high-dose dexamethasone suppression test; sensitivity, specificity, and accuracy of BIPSS in this subgroup were 100%. Conclusions:The application of a combined stimulation with CRH plus desmopressin during BIPSS is associated with a high sensitivity but no loss of specificity. (J Clin Endocrinol Metab

The role of inferior petrosal sinus sampling in ACTH-dependent Cushing's syndrome: review and joint opinion statement by members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology

“…Stimulation with desmopressin and CRH together, performed to amplify corticotrope responses, identified a central/peripheral ACTH gradient in 46 of 47 patients with Cushing's disease. 63 The use of desmopressin however might mandate additional precautions during the sampling procedure, as this agent is a known hemostatic and causes release of von Willebrand factor as well as other factors of the coagulatory cascade in patients with Cushing's disease. 46 In this context, it is worth recalling that IPSS is an invasive maneuver that requires specific expertise to achieve successful bilateral cannulation and accurate and coordinated blood sampling and minimize untoward effects.…”

Evaluation of the diagnostic criteria for Cushing’s disease in Japan [Review]

“…Gradients of sinus (central) to peripheral ACTH are calculated before and after stimulation with CRH. Cushing's disease is diagnosed when the basal gradient is greater than 2, or the gradient after stimulation is greater than 3 [34]. Administration of CRH to stimulate ACTH secretion during sampling is routinely used to elicit diagnostic gradients in Cushing's disease, and to improve the sensitivity of this procedure [34].…”

Severe hypertension and hypokalemia as first clinical manifestations in ectopic Cushing's syndrome

“…Desmopressin can also be an option for ACTH stimulation during this procedure, improving the accuracy of the differential diagnosis of ACTH-dependent Cushing's syndrome by amplifying the pituitary-peripheral ratio (7). Moreover, recent published data has suggested that the application of a combined stimulation with CRH plus desmopressin is associated with a high sensitivity without losing specificity (8).…”