Endocrine Abstracts

Background: Hydrocortisone replacement for primary adrenal insufficiency (PAI) is targeted to mimic circadian endogenous cortisol secretion. Nevertheless, patients on stable treatment report impairments in quality of life. The brain is a major target area for cortisol considering it high density of glucocorticoid receptors and previous studies in patients treated for Cushing’s disease (CD) suggest that hypothalamic-pituitary-adrenal axis dysregulation is related to cognitive impairment.

Objective: To evaluate cognitive functioning in patients with PAI and to examine the possible effect of postponing early morning hydrocortisone intake. Furthermore, we aimed to assess cognitive functioning of patients with PAI relative to patients in remission of CD.

Patients and method: Cognitive functioning was measured in 31 patients with PAI and 31 healthy matched controls using eight neuropsychological tests, evaluating memory, verbal intelligence, and executive functioning. In addition, 29 patients were included who postponed their hydrocortisone intake to after the cognitive evaluation. Cognitive functioning scores of patients in remission of CD were obtained from previous research.

Results: Compared with controls, patients with PAI performed worse on auditory and visual memory tasks (all P≤0.024) and executive functioning tasks (all P≤0.012). In contrast, patients performed better on a concentration task (P=0.015) and made less errors during a focused attention task (P=0.041). No differences were observed between patients with and those that postponed hydrocortisone intake, except for fewer repeats during a verbal fluency task (P=0.025) in patients that postponed hydrocortisone intake. Patients with PAI performed generally similar to patients in remission of CD (except for concentration and logical memory).

Conclusions: Patients on long-term hydrocortisone replacement for PAI demonstrate mild cognitive deficits compared with controls, and perform generally similar to patients in remission of CD. Future longitudinal studies are needed to provide more insight into the development and course of the observed cognitive alterations.