Patients with adrenal insufficiency (AI) are treated with glucocorticoid (GC) replacement therapy. Although current GC regimens aim to mimic the physiological circadian rhythm of cortisol secretion, temporary phases of hypo- and hypercortisolism are common undesired effects. Both conditions may lead to impairment in cognitive functioning. At present, little is known about cognitive functioning in patients with AI, especially regarding the effects of dosage and duration of glucocorticoid replacement therapy. There is also little data available comparing the effects of GC therapy on patients with primary (PAI) and secondary (SAI) forms of AI. In this study 40 adults with AI (21 PAI, 19 SAI) substituted with hydrocortisone (HC) and 20 matched healthy controls underwent 10 different neuropsychological tests evaluating memory, executive functioning, attention, psychomotricity and general intellectual ability. Furthermore demographic data, dosage of HC, duration of therapy and co-medication were evaluated. Patients were compared in groups with regard to diagnosis, dosage and duration of therapy. Patients showed worse performance than controls in attention, though patients with PAI and SAI seemed to be equally impaired. There were no limitations in intellectual abilities or memory function. High dosage of HC was found to impair attention, visual-motoric skills and executive functioning while the duration of therapy showed no significant impact on cognitive functions. In conclusion, our study showed that AI patients on HC replacement therapy reveal significant cognitive deficits concerning attention. There was no difference between patients with PAI and SAI. Furthermore, high dosage seems to have a negative impact especially on executive functioning. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.