Jorien Werumeus Buning1, Pauline Brummelman2, Janneke Koerts3, Robin P F Dullaart2, Gerrit van den Berg2, Melanie M van der Klauw2, Oliver Tucha3, Bruce H R Wolffenbuttel2, André P van Beek2. 1. 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. 2. Department of Endocrinology, University of Groningen, University Medical Center Groningen, De Brug, AA31, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. 3. Department of Clinical and Developmental Neuropsychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS Groningen, The Netherlands.
Abstract
CONTEXT: 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. 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 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.
RCT Entities:
CONTEXT: 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. 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 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: Jorien Werumeus Buning; Karl-Heinz Konopka; Pauline Brummelman; Janneke Koerts; Robin P F Dullaart; Gerrit van den Berg; Melanie M van der Klauw; Oliver Tucha; Bruce H R Wolffenbuttel; André P van Beek Journal: PLoS One Date: 2017-07-07 Impact factor: 3.240
Authors: Jorien Werumeus Buning; Jenny E Kootstra-Ros; Pauline Brummelman; Gerrit van den Berg; Melanie van der Klauw; Bruce H R Wolffenbuttel; André P van Beek; Robin P F Dullaart Journal: Eur J Clin Invest Date: 2016-04-15 Impact factor: 4.686
Authors: Annet Vulto; Ragnhildur Bergthorsdottir; Martijn van Faassen; Ido P Kema; Gudmundur Johannsson; André P van Beek Journal: Clin Endocrinol (Oxf) Date: 2019-06-20 Impact factor: 3.478