The effects of glucocorticoid treatment on cognition in patients with secondary adrenal insufficiency - results from a RCT

Abstract

Introduction: A wide variety in hydrocortisone substitution dose-regimens are considered physiological for patients with secondary adrenal insufficiency. However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. So far, no studies have been performed to assess the effects of treatment regimens administered for a substantial period of time with a low physiological hydrocortisone dose in comparison to a high physiological hydrocortisone dose on cognition. Methods: This randomized, double blind cross-over study included 47 patients (mean(SD) age, 51(14) years, range 19-73) with secondary adrenal insufficiency. Patients were randomized to either group 1 (n=22), who first received a low dose during 10 weeks followed by a high dose for another 10 weeks, or group 2 (n=25), who first received a high dose followed by a low dose. All patients received a thrice-daily weight adjusted dose, with a total daily dose of 0.2-0.3 mg/kg body weight in the low dose condition and a total daily dose of 0.4-0.6 mg/kg body weight in the high dose condition. Cognitive performance of patients was measured at baseline and after each treatment period. A battery of 11 standardized cognitive tests which resulted in 37 test scores covering 4 cognitive domains (memory, attention, executive functioning and social cognition) was used. Results: Serum cortisol levels in the high dose condition were significantly higher compared to the serum cortisol levels in the low dose condition for both study periods. No differences in cognitive performance was found between the two dose regimens, except for short term memory (15 Words Test, p = 0.028, Z-score high dose (SD) = -0.03 (1.03), Z-score low dose (SD) = 0.35 (1.01), d = 0.38) and variability of reaction time in the phasic alertness task (Test of Attentional Performance, p = 0.015, Z-score high dose (SD) = -0.42 (0.79), Z-score low dose (SD) = -0.14 (0.82), d= 0.35). Conclusion Overall, no major negative influence on memory, attention, executive functioning and social cognition was observed after 10 weeks of treatment with a higher physiological dose of hydrocortisone in patients with secondary adrenal insufficiency when compared to a lower dose. However, minor effects of high doses of hydrocortisone on aspects of attention and short-term memory are present.