title: Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing's syndrome.
abstract: The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing's syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing's syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels < 3 and < 1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy. roberta.giordano@unito.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Giordano
authors.forename: Rita
authors.initials: R
authors.lastname: Berardelli
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karamouzis
authors.forename: Valentina
authors.initials: V
authors.lastname: D'Angelo
authors.forename: Andreea
authors.initials: A
authors.lastname: Picu
authors.forename: Clizia
authors.initials: C
authors.lastname: Zichi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Fussotto
authors.forename: Maria
authors.initials: M
authors.lastname: Manzo
authors.forename: Giulio
authors.initials: G
authors.lastname: Mengozzi
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arvat
mesh_terms: D000525:Alprazolam / Q000008:administration & dosage / Q000627:therapeutic use*; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D003907:Dexamethasone; D006854:Hydrocortisone; D000525:Alprazolam