Detrimental effects of hypercortisolism on brain structure and related risk factors

Brain structural abnormalities are often observed on magnetic resonance imaging (MRI) scans of Cushing's syndrome patients, but the pathogenesis is not fully understood. To understand the relationship between brain structural abnormalities and potential risk factors in active Cushing's disease (CD) patients, a total of 101 treatment-naïve CD patients and 95 sex-, age- and education matched controls with non-functioning adenomas (NFA) underwent clinical evaluation and MRI investigation, and the relative risk factors were analyzed. 14 patients in sustained remission after transsphenoidal surgery were followed. Compared with the NFA subjects, the patients with CD had more cortical (P < 0.01) and subcortical atrophy (P < 0.01) and a higher prevalence of white matter hyperintensity (WMH) (P < 0.01). WMH severity in CD patients positively correlated with age (r = 0.532, P = 0.000), disease course (r = 0.257, P = 0.009), postprandial glucose (r = 0.278, P = 0.005), frequency of left ventricular hypertrophy (r = 0.398, P = 0.001) and hypothyroidism (r = 0.246, P = 0.014). The markers of cortical and subcortical atrophy (sylvian fissure ratio, bifrontal ratio, bicaudate ratio and third ventricle width) were positively associated with the progression of WMH in the CD patients. In the follow-up of 14 patients with CD, brain atrophy and WMH was partially reversible after correction of hypercortisolism. In conclusions, brain atrophy and WMH were more likely to appear in CD patients and were possibly partially reversible following correction of hypercortisolism.