FRI187 Increased Prolactin Secretion In Inferior Petrosal Sinus Sampling Following Desmopressin Administration In Patients With ACTH-Dependent Cushing’s Syndrome

Abstract

Abstract Disclosure: M. Guay-Gagnon: None. N. Younes: None. A. La Fontaine: None. S. Larose: None. É. Thérasse: None. A. Lacroix: None. Background: Previous studies have described an increase in central prolactin (PRL) secretion in response to corticotropin-releasing hormone (CRH) during inferior petrosal sinus sampling (IPSS) in a proportion of patients with Cushing’s disease (CD). Desmopressin is used during IPSS instead of CRH because of its wider availability, lower cost, and similar accuracy. It is unknown whether central PRL secretion can also increase after desmopressin as it does after CRH. Objective: Evaluate the central PRL response to desmopressin administration in patients with ACTH-dependent Cushing’s syndrome (CS) undergoing IPSS. Method: We conducted a retrospective study of patients who underwent IPSS in our center between January 2015 and May 2022. IPSSs using desmopressin were collected, as well as those using either CRH (1 mcg/kg IV bolus) or CRH + desmopressin for comparison. ACTH and PRL were measured in bilateral petrosal sinuses at −5, 0, and 3, 5, 10 minutes after a 10 mcg IV desmopressin bolus; simultaneous peripheral ACTH, PRL and cortisol were measured at -5, 0, 3, 5, 10, 30, 45 and 60 minutes. A >50% central PRL increase from the average of −5 and 0 minutes values to peak value was considered a positive response. Results: 30 IPSSs performed with desmopressin were included: 24 patients with CD and 6 patients with ectopic ACTH secretion (EAS). 73.3% were women and mean age was 48.2 ± 14.8 y.o. 12 patients with CD (50%) had a >50% PRL increase on at least one side. The peak PRL value and highest central/peripheral (C/P) ACTH ratio after desmopressin were ipsilateral in 10 out of 12 patients (83%). Among the 9 patients whose pathology was available, only one showed co-expression of ACTH and PRL on immunohistochemistry (IHC), along with GH. In contrast, among the 12 patients with no PRL response, 2 had ACTH and PRL co-expression, and 1 had PRL expression only. No somatic genetic USP8 analyses were performed. Among the 6 patients with EAS, none had a central or peripheral PRL response after desmopressin. 21 IPSSs with either CRH or CRH + desmopressin were collected. 14 out of 18 patients (77.8%) with CD had a >50% PRL increase after stimulation. For 10 out of these 14 patients (71.4%), peak PRL value and C/P ACTH ratio were ipsilateral. 2 out of 3 IPSSs with CRH or CRH + desmopressin in patients with EAS (one resected pulmonary neuroendocrine tumor and one occult EAS) had a >50% PRL increase after stimulation. Conclusion: In our study, 50% of IPSSs showed a significant central PRL increase after desmopressin in patients with CD, but none in patients with EAS. In IPSSs with CRH or CRH + desmopressin, a significant PRL increase was observed in 77.8% of patients with CD, and 2 out of 3 patients with EAS. On pathology, there was no correlation with PRL expression on IHC. Further research is needed to better understand the mechanisms for prolactin secretion following ACTH secretagogue administration and its potential clinical implications. Presentation: Friday, June 16, 2023