Background: The adverse effects of hypercortisolism on total human brain had been highlighted in previous neuroscience studies of Cushing’s disease (CD). However, the regional alterations associated with hypercortisolism remains unclear. The present study was carried out to examine gray matter (GM) alterations according to the different stages of chronic hypercortisolism exposure.

Design: Although longitudinal studies have been traditionally used to address the question of reversibility of brain alterations in CD, these studies would probably ignore the irreversible alterations induced by hypercortisolism. Thus, information from cross-sectional neuroimaging studies may provide more useful contributions to further clarify this issue.

Methods: To examine the GM alterations during hypercortisolism exposure and after resolution of the condition, ROI-based GM volumes (GMvs) of active and two biochemically remitted CD patient groups, as well as those of healthy control subjects were compared using the F test of one-way ANOVA.

Results: Cross-sectional analysis demonstrated significant altered GMvs in most of the brain sub-regions. Moreover, different relationship between clinical characteristic and regional GMvs and diverse trends after resolution of hypercortisolism were found in CD patients, which suggested different response to the hypercortisolism in different brain sub-regions.

Conclusion: Our study enhances the understanding of the structural alterations due to hypercortisolism. Furthermore, our study may facilitate the development of future studies with neuropsychological tests.