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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

Departments of Endocrinology, Diabetes and Metabolism (S.T., D.V., J.K., E.S., N.T.) and Radiology (I.S.K.), Evangelismos Hospital, 105 052 Athens, Greece

Address all correspondence and requests for reprints to: Dr. S. Tsagarakis, M.D., Ph.D., Department of Endocrinology, Athens Polyclinic Hospital, 105 052 Athens, Greece. E-mail: stsagara{at}otenet.gr.

Context: Although bilateral inferior petrosal sinus sampling (BIPSS) 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.

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				M. Boscaro and G. Arnaldi Approach to the Patient with Possible Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3121 - 3131. [Abstract] [Full Text] [PDF]

				F Castinetti, I Morange, H Dufour, P Jaquet, B Conte-Devolx, N Girard, and T Brue Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing's syndrome Eur. J. Endocrinol., September 1, 2007; 157(3): 271 - 277. [Abstract] [Full Text] [PDF]