The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency - Results from a randomized controlled trial

Context: A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with secondary adrenal insufficiency (SAD. However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. Objective: To examine the effects of a high physiological HC dose in comparison to a low physiological HC dose on cognition. Design and setting: This study was a randomized double blind cross-over study at the University Medical Center Groningen. This study is registered with ClinicalTrials.gov, number NCT01546922. Patients: Forty-seven patients (29 males, 18 females; mean [SD] age, 51 [14] years, range 19-73) with SAI participated. Intervention(s): Patients randomly received first a low dose of HC (0.2-0.3 mg/kg body weight/day) during 10 weeks followed by a high dose (0.4-0.6 mg/kg body weight/day) for another 10 weeks, or vice versa. HC substitution was given in three divided doses with the highest dose in the morning. Main outcome measure(s): Cognitive performance (memory, attention, executive functioning and social cognition) of patients was measured at baseline and after each treatment period using a battery of 12 standardized cognitive tests. Results: The higher dose of HC resulted in significantly higher systemic cortisol exposure for example measured at 1 h after first dose ingestion (mean [SD], low dose: 653 [281] nmol/L; high dose: 930 [148] nmol/L; P<0.001). No differences in cognitive performance were found between the two dose regimens. Conclusions: No negative influence on memory, attention, executive functioning and social cognition was observed after 10 weeks of treatment with a higher physiological dose of HC in patients with SAI when compared to a lower dose. (C) 2015 Elsevier Ltd. All rights reserved.