Brain Metabolism Altered in Patients with Cushing’s Disease, Study Finds

Certain regions of the brain in patients with Cushing’s disease are associated with altered metabolism, indicating a mechanism of cognitive impairment, new study shows.

The study, “Voxel-based comparison of brain glucose metabolism between patients with Cushing’s disease and healthy subjects,” was published in the journal NeuroImage: Clinical.

Excessive cortisol, as seen in patients with Cushing’s disease (CD), is associated with many symptoms, including cognitive impairment and psychiatric problems. This can lead to an impaired quality of life as symptoms often persist, even after treatment. So it is necessary to determine how cortisol leads to these neuropsychiatric symptoms.

Studies have shown that certain regions of the brain, particularly those that are involved in regulation and activity of cortisol, such as the hippocampus, the amygdala, and the cerebellum, undergo structural changes.

Radiological imaging, such as magnetic resonance imaging (MRI), has been shown to be a reliable and noninvasive way to explore the changes that occur in the brain when exposed to high levels of cortisol.

In particular, [18F]-Fluorodeoxyglucose positron emission tomography (FDG PET) has emerged as a way of determining functional changes in the brains of patients with cognitive disorders. FDG is a glucose-like compound that is metabolized by the brain and therefore, can provide insight on the metabolic changes in the brain.

Researchers in China used the FDG PET method to determine the changes in brain metabolism associated with serum cortisol levels in patients with Cushing’s compared to healthy people.

In the first part of the study, researchers determined that Cushing’s disease patients and healthy individuals exhibited different FDG metabolism in particular parts of the brain.

Regions such as the hippocampus, amygdala, basal ganglia, and cerebellum showed significantly higher FDG uptake in Cushing’s patients. However, there was a significantly decreased uptake of FDG in the cerebral cortex.

Interestingly, the metabolic rate of these regions, as determined by FDG uptake, was found to be significantly correlated to serum cortisol levels.

As the hippocampus, the amygdala, cerebellum, and the basal ganglia in Cushing’s disease patients had a significantly higher metabolic rate, this indicates high levels of cortisol-induced neurotoxic effects on these regions of the brain.

Therefore, the different metabolic rate in patients with CD, caused by high levels of cortisol, may explain the cognitive issues in these patients.

“Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up,” the authors concluded.