Endocrine Abstracts

Subclinical Cushing’s syndrome (SCS) is a status of altered hypothalamo-pituitary-adrenal (HPA)-axis secretion in the absence of the classical signs or symptoms of overt cortisol excess. Among the various tests used for the diagnosis of SCS, the 1-mg dexamethasone test (DST) is the most used. Alprazolam (ALP), a benzodiazepine activating GABAergic receptors, possesses clear centrally-mediated inhibitory effects on ACTH and cortisol secretion in normal subjects, while it does not modify ACTH and cortisol hypersecretion in patients with overt hypercortisolism.

Aim of the study was to verify the effect of alprazolam (1 mg p.o. at 23.00 h) on the cortisol response to DST test (1 mg at 24.00 h) in 22 patients with adrenal adenomas (AA) and SCS (14♀ and 8♂, age: 66.3±1.8 years), 11 patients with non-functioning AA (NF, 7♀ and 4♂;55.9±2.9), 10 patients with overt Cushing’s syndrome (five of adrenal nature, CS, 4♀ and 1♂,42.0±3.8; 5 with Cushing’s disease, CD, 4♀ and 1♂,58.0±5.6). 14 normal subjects (NS, 9♀ and 5♂;55.8±2.2) were enrolled as controls. SCS was defined by a post-DST cortisol level>1.8 μg/dl and one of the following: midnight serum cortisol>7.5 μg/dl, ACTH<5 pg/ml or UFC>100 μg/24 h. ALP reduced cortisol secretion after DST in patients with SCS (P<0.05), while it was ineffective in CS and CD patients. ALP pre-treatment reduced cortisol values <1.8 μg/dl in five patients with SCS but in none CS or CD. All NF and NS showed cortisol levels <1.8 μg/dl after DST and ALP+DST.

These data demonstrate that GABAergic activation by ALP still modulates adrenal hyperfunction in patients with subclinical hypercortisolism but not in those with overt disease, suggesting only a partial autonomous adrenal cortisol secretion in SCS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST in distinguishing functional from organic subclinical hypercortisolism should be confirmed.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.