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 (S.D.) age, 51(14) years, range 1973) with secondary adrenal insufficiency. Patients randomly received first a low dose hydrocortisone (0.20.3 mg/kg body weight) during 10 weeks followed by a high dose (0.40.6 mg/kg body weight) for another 10 weeks, or vice versa. Cognitive performance of patients was measured at baseline and after each treatment period. A battery of 11 standardized cognitive tests covering 4 cognitive domains (memory, attention, executive functioning and social cognition) was used.
Results: Patients in the high dose condition scored significantly worse on short term memory (15 Words Test, P=0.028, Z-score low dose (S.D.)=0.35 (1.01), Z-score high dose (S.D.)=−0.03 (1.03), d=0.38) and showed a higher variability of reaction time in the phasic alertness task (Test of Attentional Performance, P=0.015, Z-score low dose (S.D.)=−0.14 (0.82), Z-score high dose (S.D.)=−0.42 (0.79), d=0.35) compared to patients in the low dose condition. A trend towards more impaired scores on social cognition (P=0.065) and fewer impaired scores on psychomotor speed (P=0.092) was observed in the low dose condition. No differences were found on the other measures of cognitive performance.
Conclusion: In patients with secondary adrenal insufficiency, a higher physiological dose of hydrocortisone has a negative influence on short-term memory and aspects of attention compared to a lower dose after 10 weeks of treatment.