(CSEMP069) INCREASED PROLACTIN SECRETION IN INFERIOR PETROSAL SINUS SAMPLING FOLLOWING DESMOPRESSIN ADMINISTRATION IN PATIENTS WITH ACTH-DEPENDENT CUSHING'S SYNDROME

Abstract:

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 now used 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 2015 and 2022. IPSSs using desmopressin were collected, as well as those using either CRH or CRH + desmopressin for comparison. ACTH and PRL were measured in bilateral petrosal sinuses before and 3, 5, and 10 minutes after a 10 mcg IV desmopressin bolus; and simultaneous peripheral ACTH, PRL and cortisol were measured. A >50% central PRL increase 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 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). 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 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 had a >50% PRL increase after stimulation.

Conclusion: In our study, 50% of IPSSs showed a significant central prolactin increase after desmopressin in patients with CD, but none in patients with EAS. In pathology of corticotroph adenomas from patients with prolactin stimulation by desmopressin, there was no expression of prolactin by IHC. Further research is needed to better understand the mechanisms for prolactin secretion following ACTH secretagogue administration and its potential clinical implications.