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Background Patients with adrenal insufficiency (AI) are treated with glucocorticoid replacement therapy (GRT). Although current glucocorticoid regimens aim to mimic the physiological circadian rhythm of cortisol secretion, temporary phases of hypo- and hypercortisolism are common undesired effects which lead to a variety of consequences like increased cardiovascular risk and premature mortality. Additionally, poor quality of life (QoL) and impaired sleep have been reported. However, little is known about these topics regarding the effects of daily dosage, duration of therapy, and patients with different forms of AI (primary, PAI, and secondary, SAI). Methods In this study, 40 adults with AI substituted with hydrocortisone (HC) and 20 matched healthy controls completed questionnaires evaluating depressive symptoms, subjective health status, quality of sleep and daytime sleepiness. Furthermore, demographic data, dosage of HC, duration of therapy and co-medication were evaluated. Patients were compared in different groups. Results Patients assessed general health significantly worse than controls; likewise, daytime sleepiness was reported significantly more often. Depressive symptoms differed significantly in the two groups but did not reach clinically relevant scores. There was no difference between patients with PAI and SAI. High dosage of hydrocortisone had negative impact on mental health but not on sleep quality or daytime sleepiness. Conclusions The present data highlight that poor QoL and impaired sleep are still severe and underrated issues in current GRT and might be additional factors for premature mortality in patients with AI. Some AI patients reach normal or near-normal self-assessed QoL and sleep, even despite unphysiological replacement.

Introduction Patients with primary and secondary adrenal insufficiency (PAI/ SAI) are usually treated with glucocorticoid replacement therapy which fails to mimic the circadian rhythm of cortisol secretion thereby resulting in temporary hypo- and hypercortisolism. The unphysiological replacement is associated with impairment in cognitive function. Dual-release hydrocortisone (DR-HC) resembles the daily normal cortisol profile which improves metabolic parameters and quality of life but currently little is known about its impact on cognitive function. Material and Methods Twenty adults with adrenal insufficiency (12 PAI, 8 SAI) treated with DR-HC underwent 10 neuropsychological tests, evaluating intellectual abilities, mindset, memory, executive functioning, attention and alertness. Furthermore, demographic data, quality of life, symptoms of depression and quality of sleep were evaluated by well-established questionnaires (AddiQoL, SF-36, Beck Depression Inventory, Pittsburgh sleep quality index). Patients were split into 2 groups with respect to diagnosis (PAI vs. SAI) and to dosage (≤20mg/d vs. >20 mg/d, defined by median split). Because of use of standardized tests all patients could be compared to healthy controls. Moreover eighteen DR-HC treated adults were compared with eighteen adults on conventional-HC treatment matched for age, sex, education and diagnosis. Results Compared to standard values patients on DR-HC reached improved scores in intellectual abilities (p=0.000) and memory (p=0.001) and impaired scores in alertness (p=0.000). With respect to diagnosis patients with PAI performed better on intellectual abilities (IQ 121.3 vs. 103.8; p=0.038) and on executive functioning (79.2% vs. 45.0%; p=0.026) and reported a longer time to fall asleep (36 min. vs. 12 min.; p=0.026) than patients with SAI. Regarding DR-HC dosage, there was no significant difference in cognitive function. Patients on high dose reported a better subjective quality of sleep (p=0.028) than patients on low dose. In comparison to conventional-HC treatment, patients with DR-HC tended to show better results in executive functioning (59.2% vs. 66.1%; p=0.099). We found no further significant differences between both treatment modalities. Conclusion Patients with PAI reached better results in several cognitive functions and had a worse quality of sleep than patients with SAI. Our data suggest a positive impact of DR-HC on quality of sleep. DR-HC may be better for executive functioning than conventional-HC.