478. Saccadic eye movement responses to DHEA & alprazolam in patients with adrenal insuffiency

Abstract

Patients with adrenal insufficiency (AI) are an ideal population for evaluating physiological effects of circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA-S. Secreted by the adrenal cortex in response to adrenocorticotropin, these neurosteroids are in vitro negative modulators of the GABAA-receptor. The study was designed to assess the effects of DHEA and the GABA-agonist alprazolam (ALP) on saccadic eye movements (SEMs) in 4 AI patients and matched control subjects. The study was a randomized, double-blind, placebo-controlled, crossover with treatments of placebo, DHEA, ALP, and ALP+DHEA. On each study day, blood samples were obtained and SEMs were assessed at 10 sessions in 12 hours after single-day oral administration of study drug(s). Patients with AI had lower DHEA and DHEA-S than control subjects in the placebo treatment (p < 0.0001). After DHEA, there were similar DHEA-S, but lower DHEA concentrations in AI subjects. Baseline SEMs were similar for both groups. AI and controls missed 7 and 1 sessions, respectively due to impairment. After ALP and ALP+DHEA, 5 and 3 sessions were missed, respectively. Peak SEM velocity (VEL) was faster (2) or equal (2) after ALP+DH than after ALP in AI; in controls, VEL was slower (3) or equal (1), respectively. These data from a limited number of subjects suggest that single day DHEA ameliorates ALP-induced slowing of VEL in patients with AI. In controls, DHEA worsens impairment. Since SEM VEL is a GABAA-receptor mediated response not under voluntary control, these data support justification for administering DHEA to patients with AI, but not to healthy individuals.