Chronic exposure to high circulating levels of glucocorticoids has detrimental effects in health, including metabolic abnormalities, as exemplified in Cushing’s Syndrome (CS). Magnetic Resonance Imaging(MRI) studies have found volumetric changes in gray and white of the brain, in CS patients during the course of active disease, but also in remission. In order to explore this further, we performed brain volumetric analyses in AdKO mice. The AdKO mouse is an accurate model for CS, as it presents key traits of it (i.e. hypercorticosteronemia, female alopecia, central obesity, and fat deposition in the back of the neck (“buffalo hump”)). The results indicate that AdKO mice have smaller volumes in several brain regions. Furthermore, we found an increase in Myelin Basic Protein (MBP, an oligodendrocyte marker) expression in the cingular cortex (Cg), as well as a decrease in the expression of GFAP (Glial Fibrilary Acidic Protein, a marker for reactive astrocytes) and IBA1 (Ionized calcium-Binding Adapter molecule 1, a marker for microglia) in the Cingular regions of the Anterior Corpus Callosum (ACC). We also found reductions for the three markers in Hippocampus. These results indicate that long term hypercorticosteronemia might result in abberant myelination, and that there might be a degree of white matter damage, as both repair (GFAP) and immune (IBA1) responses are decreased. These findings bring light about a probable cause for the changes observed in the brains of human patients, and serve as a background for further exploration of their subcellular and molecular mechanisms.