A Multicenter Comparison of CRH versus DDAVP Stimulation Responses in Inferior Petrosal Sinus Sampling for Cushing’s Disease

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 multicenter 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: Out of 780 patients, 108 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 differences 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 versus 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 2.7× increase in ACTH for both DDAVP vs. CRH paradigms. CRH stimulation peaked earlier than DDAVP, showing a 6.2× increase in ACTH at 2 minutes, compared to 2.0× 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 to 2.7× after DDAVP stimulation at 2 to 5 minutes may help identify ACTH lateralization thresholds for DDAVP.

Fig. 1 Normalized ACTH levels for DDAVP vs. CRH stimulation during IPSS for localized sides.

Fig. 2 Comparison of normalized ACTH after DDAVP or CRH stimulation.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
07 February 2025