title: The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency--results from a randomized controlled trial.
abstract: BACKGROUND
  A 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.
  
  
  OBJECTIVE
  To examine the effects of a high physiological HC dose in comparison to a low physiological HC dose on cognition.
  
  
  METHODS
  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.
  
  
  METHODS
  Forty-seven patients (29 males, 18 females; mean [SD] age, 51 [14] years, range 19-73) with SAI participated.
  
  
  METHODS
  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.
  
  
  METHODS
  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 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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Jorien
authors.initials: J
authors.lastname: Werumeus Buning
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Brummelman
authors.affiliation: Department of Clinical and Developmental Neuropsychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS Groningen, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Koerts
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: van den Berg
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: van der Klauw
authors.affiliation: Department of Clinical and Developmental Neuropsychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS Groningen, The Netherlands.
authors.forename: Oliver
authors.initials: O
authors.lastname: Tucha
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
authors.forename: André P
authors.initials: AP
authors.lastname: van Beek
mesh_terms: D000309:Adrenal Insufficiency / Q000188:drug therapy* / Q000523:psychology; D000328:Adult; D000368:Aged; D001288:Attention; D003071:Cognition; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D056344:Executive Function; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D012938:Social Perception; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D006854:Hydrocortisone
keywords: Cognition; Hydrocortisone; Secondary adrenal insufficiency