Adrenocorticotropin responsiveness to acute octreotide administration is not affected by mifepristone premedication in patients with Cushing’s disease

Octreotide (OCT) is ineffective in patients with Cushing’s disease (CD) due to the cortisol-induced down-regulation of somatostatin receptor subtype 2 which was shown to be reversible in vitro by using anti-glucocorticoid mifepristone. This study aimed to verify, in vivo, if mifepristone can modulate response to acute OCT administration in patients with CD. Three men and two postmenopausal women (age 52.5 ± 2 years) with CD were enrolled in the study. OCT (100 μg, s.c.) was administered alone on the first day (OCT-only), and it was then given after mifepristone administration (2 × 200 mg, p.os, 12 and 1 h before OCT), 3 days later (OCT-mif). ACTH and cortisol levels were measured before OCT administration and every 60 min thereafter for 6 h. Baseline ACTH and cortisol values, nadir values and percentage decrements (Δn) were compared during both tests. Mean ACTH-Δn did not differ significantly during the two tests. Both tests induced a <30 % decrease in plasma ACTH in three patients (#1, 2 and 3) and a >50 % decrease in the other two cases (#4 and 5). Cortisol decreased in patients #4 and 5, during both tests. ACTH-Δn did not correlate with morning cortisol nor with urinary free cortisol values. Patients #4 and 5 with the highest ACTH-Δn had the lowest cortisol values after 1 mg of dexamethasone. Brief mifepristone pre-treatment does not modify ACTH and cortisol response to acute OCT administration in CD. However, OCT seems to be more effective in patients with partially preserved cortisol inhibitory feedback.