title: Adrenocorticotropin responsiveness to acute octreotide administration is not affected by mifepristone premedication in patients with Cushing's disease.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino" (Pad. H, 4th Floor), Via Consolare Valeria 1, 98125, Messina, Italy, francesco.ferrau1@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrau
authors.forename: Francesco
authors.initials: F
authors.lastname: Trimarchi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cannavo
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000627:therapeutic use*; D015282:Octreotide / Q000494:pharmacology*; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000188:drug therapy*
chemical_list: D006727:Hormone Antagonists; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone; D015282:Octreotide