2025 Proffered Presentations
S020: A MULTI-CENTER COMPARISON OF CRH VS. DDAVP STIMULATION RESPONSES IN INFERIOR PETROSAL SINUS SAMPLING FOR CUSHING'S DISEASE
Michael Karsy1; Julie Silverstein2; Albert Kim2; James Evans3; Sarah Collopy3; Robert Rennert4; William Couldwell4; Garni Barkhoudarian5; Dan Kelly5; Juan Fernandez-Miranda6; Donato Pacione7; Won Kim8; Marvin Bergsneider8; Michael Chicoine9; Gabriel Zada10; Varun Kshettry11; Kyle Wu12; Carolina Benjamin13; Jamie Van Gompel14; Michael Catalino15; Adam Mamelak16; Nathan Zwagerman17; Andrew Little18; Kevin Yuen18; Ildiko ITorok18; Paul Gardner19; 1Drexel University College of Medicine; 2Washington University School of Medicine; 3Jefferson University; 4University of Utah; 5Pacific Neuroscience Institute; 6Stanford University; 7New York University; 8University of California, Los Angeles; 9University of Missouri, Columbia; 10Keck School of Medicine, University of Southern California; 11Cleveland Clinic Foundation; 12Ohio State College of Medicine, Ohio State University; 13Miller School of Medicine, University of Miami; 14Mayo Clinic; 15University of Virginia; 16Cedars-Sinai Medical Center; 17Medical College of Wisconsin; 18Barrow Neurological Institute; 19University of Pittsburgh Medical Center
Introduction: Inferior petrosal sinus sampling (IPSS) is an important method for confirming a central source of hypercortisolism and diagnosis of Cushing’s disease (CD). IPSS can be especially helpful in MRI-negative disease or unclear sources of adrenocorticotropin hormone (ACTH). Recently, centers are stimulating with desmopressin/DDAVP instead of corticotropin releasing hormone (CRH) due to reagent availability. To study the potential clinical implications of this change, we compared the stimulation profiles of DDAVP and CRH in the multi-center Registry of Adenomas of the PItuitary and Related Disorders (RAPID).
Methods: Patients who underwent IPSS for management of CD were included. A descriptive analysis of surgical characteristics and laboratory values as well as stimulation protocols and response were performed. Changes in ACTH level on the IPSS localized and nonlocalized sides were compared after DDAVP or CRH stimulation. ACTH levels were normalized to peripheral levels.
Results: 108/780 patients with CD underwent IPSS testing. Among patients with IPSS, 93/108 (86.11%) demonstrated positive pathology or long-term hormonal remission. Stimulation agents included DDAVP (n=57), CRH (n=36) or both (n=1). No difference in demographic, surgical or pathology characteristics were seen between DDAVP or CRH patients (p>0.05). Long-term remission was similar for treated patients after DDAVP vs. CRH stimulation (66.7% vs. 74.1%; p=0.05) workup with a mean follow-up of 28.8±25.2 and 24.9±24.7 months. Peak ACTH levels of 44.7±73.1 and 57.1±70.0 pg/ml at 5 minutes (p=0.4) corresponded to a 2.7X increase in ACTH for both DDAVP vs. CRH paradigms. CRH stimulation peaked earlier than DDAVP, showing a 6.2X increase in ACTH at 2 minutes, compared to 2.0X for DDAVP.
Discussion: CRH stimulation showed a more robust stimulation response than DDAVP for localizing ACTH levels during IPSS at 2 minutes but both agents showed efficacy at 5 minutes. Given the limited availability of CRH, elevations of ACTH of 2.0-2.7X after DDAVP stimulation at 2-5 minutes may help identify ACTH lateralization thresholds for DDAVP.
Figure 1: Normalized ACTH levels for DDAVP vs. CRH stimulation during IPSS for localized sides
Figure 2: Comparison of normalized ACTH after DDAVP or CRH stimulation