Brain Tissue Changes in Cushing’s Syndrome May Correlate with Disease Symptoms, Study Suggests

In addition to changes in volume of certain brain structures, people with Cushing’s syndrome also show widespread changes in the consistency of brain tissue, namely in white matter, which is made of nerve fibers or axons.  Importantly, such changes may correlate with disease symptoms.

The study with those findings, “Computerized analysis of brain MRI parameters dynamics in young patients with Cushing Syndrome – a case-control study,” was published in the Journal of Clinical Endocrinology & Metabolism.

Cushing’s is caused by excess cortisol in the body (hypercortisolism). Alongside several physical manifestations, Cushing’s syndrome also is associated with neuropsychiatric and cognitive symptoms, indicating involvement of the central nervous system (brain and spinal cord).

Studies of Cushing’s patients have shown reduction of the hippocampus and cortex’s volume. The hippocampus has a major role in learning and memory, while the cortex is responsible for many functions, including language and information processing.

Knowing this, investigators at the Eunice Kennedy Shriver National Institute of Child Health and Human Development set out to analyze the changes in brain magnetic resonance imaging (MRI) parameters in patients with persistently high levels of cortisol, in people in remission, and in healthy (control) subjects.

To better understand the implications of Cushing’s on the brain, the team analyzed two consecutive MRI scans for everyone in the study sample. MRI data was crossed with both cortisol levels and Cushing’s syndrome status (persistent or resolved).

Researchers examined MRI scans of 37 subjects (median age 14 years), including eight controls and 29 patients — eight with unresolved Cushing’s and 21 in remission. Among patients, 12 had Cushing’s disease (meaning their Cushing’s was caused by a tumor in the pituitary gland), 15 had adrenal Cushing’s, and two had ectopic Cushing’s syndrome (caused by a tumor elsewhere in the body).

The team found that higher cortisol levels, measured through a 24-hour cortisol urine test, correlated significantly with lower activity in the subcortical gray matter, in the total cerebral white matter, and in the corpus callosum.

The brain is composed of gray and white matter. The first consists of cell bodies — the control center of neurons — while the latter is made up of nerve cell projections, known as axons or fibers, connecting distinct parts of gray matter. The corpus callosum is a thick band of nerve fibers that divides the cerebral cortex lobes into left and right hemispheres.

There was a more pronounced increase in white matter volume in patients with persistent Cushing’s syndrome, compared to those in remission, and a reduced white matter volume in patients achieving remission, in comparison to controls.

This could be explained by the fact that cortisol stimulates the production of myelin (the protective covering of nerve fibers), which increases white matter volume. On the other hand, when the excess cortisol resolves, the sharp decrease in cortisol levels could damage the myelin layer, thus provoking a decrease in white matter volume.

In comparison to controls, patients with resolved Cushing’s syndrome had a higher growth in cortical thickness of the frontal lobe, a highly cognitive area. This finding is supported by previous evidence indicating the brain is able to recover from cortisol damage following appropriate Cushing’s treatment.

Researchers concluded that, in the context of Cushing’s syndrome, changes in white and gray matter consistency may correlate better with the clinical manifestations of the disease than volume changes alone.