Mild cognitive deficits in patients on stable treatment for primary adrenal insufficiency

Abstract

Background: The brain is a major target area for cortisol considering its high density of glucocorticoid receptors. Previous studies in patients treated for hypercortisolism, such as in Cushing’s disease (CD), suggest that hypothalamic–pituitary–adrenal axis dysregulation is related to cognitive impairment. However, there is a very limited body of research on the effects of hypocortisolism on cognitive functioning. Aim: To evaluate cognitive functioning in patients with hypocortisolism (primary adrenal insufficiency (PAI)) and to examine thepossible effect of postponing early-morningHydrocortisone intake. Furthermore,we aimed to compare cognitive functioning of patients with PAI to patients with CD. Methods: Thirty-one patients with PAI and 31 healthymatched controls underwent eight neuropsychological tests, evaluating memory and executive functioning. An additional 29 patients with PAI were included who postponed their morning Hydrocortisone intake. Scores of patients in remission of CD were obtained from previous research. Results: Compared to 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 and an attention task (both P<0.05).No importantdifferenceswereobservedbetweenpatients with andwithout Hydrocortisone intake, or between patients with PAI and patients in remission of CD. Conclusion: The present study demonstrates that patients on long-term Hydrocortisone replacement for PAI show mild cognitive deficits compared to 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.