Endocrine Abstracts

Background: Alongside various physical symptoms, patients with high levels of cortisol, such as typically found in Cushing’s disease, often display a wide variety of neuropsychiatric symptoms such as depression, psychosis, mania and cognitive impairments. This indicates involvement of the central nervous system in hypercortisolism.

Methods: Various neuroimaging approaches can be used to examine the effects of hypercortisolism on the brain. The frequently used structural magnetic resonance imaging (MRI) techniques allow detection of alterations of volume or shape of brain regions or in local grey matter volume. Common functional MRI (fMRI) designs detect changes in task related activity. More novel approaches, such as resting-state fMRI or diffusion tensor imaging (DTI) focus on structural and functional connectivity between brain regions.

Results: Early structural MRI studies in Cushing’s disease found indications for bilateral reductions of the volume of the hippocampus and the cerebellum. More recent structural MRI studies also implicate the amygdala and the medial prefrontal cortex, not only in active, but also in remitted hypercortisolism. In addition, specific diffuse alterations of white matter connectivity, suggestive of demyelination were found in both conditions. Furthermore, patients also show disturbed resting state functional connectivity, altered activity during the processing of emotional information and changes in markers of neuronal viability. Data suggests partial reversibility of these functional and structural MRI findings, but longitudinal studies are lacking.

Conclusion: Patients with current or past (endogenous) hypercortisolism show alterations of structure, activity and connectivity of brain circuitry involved in emotion regulation and cognitive processes. Longitudinal studies are lacking and translational approaches are needed to further elucidate the underlying processes.