Background – Young patients with Cushing Syndrome (CS) may develop cognitive and behavioral alterations during disease course.

Methods - To define the implications of CS on the brain, we analyzed consecutive MRI scans of patients with (n=29) vs. without CS (n=8). Multiple brain compartments were processed for total and gray/white matter (GM/WM) volumes and intensities; and cortical volume, thickness and surface-area. Dynamics (last/baseline scans ratio per parameter) were analyzed vs. cortisol levels and CS status (persistent, resolved and non-CS).

Results - 24-hour urinary free cortisol (24hUFC) measurements had inverse correlation with the intensity of subcortical GM structures and of the corpus callosum, and with the cerebral WM intensity. 24hUFC dynamics had negative correlation with volume dynamics of multiple cerebral and cerebellar structures. Patients with persistent CS had less increase in cortical thickness and WM intensity, and less decrease in WM volume compared with patients with resolution of CS. Patients with resolution of their CS had less increase in subcortical GM and cerebral WM volumes, but more increase in cortical thickness of frontal lobe vs. controls.

Conclusion - Changes in WM/GM consistency, intensity and homogeneity in patients with CS, may correlate with CS clinical consequences better than volume dynamics alone.

Supplementary table 1 Comparison of brain MRI parameters, between patients with CS achieving vs. not achieving remission

Supplementary table 2 Comparison of brain MRI parameter dynamics between patients with CS achieving remission vs. controls