Altered microstructural pattern of white matter in Cushing’s disease identified by automated fiber quantification

A growing body of evidence suggests that altered brain structure plays a crucial role in the pathogenesis of neuropsychological abnormalities induced by hypercortisolism in patients with Cushing’s disease. While most studies mainly focus on gray matter, white matter structure has been largely overlooked. In the current study, we conducted a cross-sectional diffusion tensor imaging study on 58 patients with Cushing’s disease and 54 matched healthy individuals to profile the microstructural pattern using automated fiber quantification and investigate its association with neuroendocrine and neuropsychological deficits. The study revealed that microstructural pattern showed a widespread mean diffusivity, radial diffusivity increase, fractional anisotropy decrease and partial axial diffusivity increase among tracts notably in corpus callosum forceps, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus and arcuate fasciculus, while within the same tract abnormalities localized to specific positions. Moreover, compromised microstructural pattern of white matter in specific tracts and locations along the trajectory were associated with ACTH and cortisol concentration and cognitive decline in patients with Cushing’s disease. Collectively, our study elucidates the form of white matter pathology induced by hypercortisolism and its association with cognitive decline which may provide further targets for early identification and intervention of Cushing’s disease.