• Jorien Werumeus Buning, Pauline Brummelman, Janneke Koerts, Robin P F Dullaart, Gerrit van den Berg, Melanie M van der Klauw, Oliver Tucha, Bruce H R Wolffenbuttel, and André P van Beek.
• Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Electronic address: j.werumeus.buning@umcg.nl.
• Psychoneuroendocrinology. 2015 May 1; 55: 36-47.

ContextA wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with secondary adrenal insufficiency (SAI). However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain.ObjectiveTo examine the effects of a high physiological HC dose in comparison to a low physiological HC dose on cognition.Design And SettingThis study was a randomized double blind cross-over study at the University Medical Center Groningen. This study is registered with ClinicalTrials.gov, number NCT01546922.PatientsForty-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.ResultsThe higher dose of HC resulted in significantly higher systemic cortisol exposure for example measured at 1h 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.ConclusionsNo 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.Copyright © 2015 Elsevier Ltd. All rights reserved.

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