Structural and functional brain alterations in Cushing’s disease: A narrative review

Neurocognitive and psychiatric symptoms are non-negligible in Cushing’s disease and are accompanied by structural and functional alterations of the brain. In this review, we have summarized multimodal neuroimaging and neurophysiological studies to highlight the current and historical understandings of the structural and functional brain alterations in Cushing’s disease. Specifically, structural studies showed atrophy of the gray matter, loss of white matter integrity, and demyelination in widespread brain regions. Functional imaging studies have identified three major functional brain connectome networks influenced by hypercortisolemia: the limbic network, the default mode network, and the executive control network. After endocrinological remission, atrophy of gray matter regions and the compromised functional network activities were partially reversible, and the widespread white matter integrity alterations cannot recover in years. In conclusion, Cushing’s disease patients display structural and functional brain connectomic alterations, which provides insights into the neurocognitive and psychiatric symptoms observed in this disease.