Reversibility of Cerebral Atrophy in Cushing's Disease
Cerebral atrophy has been shown to be reversible in patients with Cushing's disease. Following resection of adrenocorticotropin hormone-secreting pituitary adenomas, hippocampal formation volume has been shown to increase by as much as 10%. The increase in hippocampal formation volume correlates with the magnitude of decrease in urinary free cortisol. In addition, improvements in memory correlate with decreases in cortisol levels as well as with increases in hippocampal formation volume. Age has been identified as a significant factor that influences the speed of recovery. Younger patients regain and sustain their improvement in cognitive functioning more quickly than older subjects. These findings suggest that at least some of the deleterious effects of prolonged hyper-cortisolemia on cognitive functioning and hippocampal volume are reversible.
In summary, Cushing's disease is associated with hippocampal and generalized brain atrophy. Excess glucocorticoids cause retraction and simplification of dendrites in the hippocampus, and these morphological changes probably account for the hippocampal volume loss. Furthermore, a profound loss of synapses is also seen in Cushing's disease. These findings suggest the possibility that volume measures may be underestimating the change in neural structures. Several mechanisms by which glucocorticoids affect the brain include decreased neurogenesis, glucose utilization, and synthesis of neurotrophic factors as well as increased actions of EAA. We have reviewed the evidence correlating hippocampal atrophy and cognitive deficits and have shown that these effects appear to reversible. Further investigations into the mechanisms by which glucocorticoids affect the brain and peripheral tissues are essential. These mechanistic details may eventually provide targets for preventing or treating the brain atrophy, cognitive impairments, and mood disorders common in patients with Cushing's disease.