Effects of short-term nocturnal cortisol replacement on cognitive function and quality of life in patients with primary or secondary adrenal insufficiency: a pilot study.

Cortisol replacement in patients with adrenal insufficiency usually consists of hydrocortisone (HC) given orally during day time. Due to the short half-life of hydrocortisone, cortisol levels between midnight and early morning are very low in contrast to the physiological rise of cortisol serum levels during this time. We investigated whether short-term cortisol replacement during the night improves cognitive function and well-being in these patients. Fourteen patients with adrenal insufficiency were put on HC infusion between midnight and 8 a.m. They subsequently underwent neurocognitive testing to measure intellectual functioning, concentration, memory and fine motor skills. Quality of life and mood were also evaluated. All tests were repeated after 2-4 weeks during usual oral glucocorticoid replacement therapy. Blood samples were taken for cortisol, epinephrine and norepinephrine measurement. With the exception of the digit symbol test with better scoring in the oral group (p = 0.005) there were no significant differences in neurocognitive testing, vegetative functions and quality of life on the two occasions. However, a higher cortisol level was associated with a worse performance in short-term memory. Plasma epinephrine concentration was subnormal in both groups, but increased only after intravenous hydrocortisone replacement. Mimicking the physiological rise in cortisol secretion during the night in this pilot study did neither significantly affect quality of life nor cognitive performance and vegetative functions. There was no improvement in general well being. Hydrocortisone infusion during night time might improve adrenomedullary reserve in patients with adrenal insufficiency.