Hippocampal and cerebellar atrophy in patients with Cushing’s disease

Abstract

<jats:sec> <jats:title>OBJECT</jats:title> <jats:p>Cushing’s disease (CD) may cause atrophy of different regions of the human brain, mostly affecting the hippocampus and the cerebellum. This study evaluates the use of 3-T MRI of newly diagnosed patients with CD to detect atrophic degeneration with voxel-based volumetry.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>Subjects with newly diagnosed, untreated CD were included and underwent 3-T MRI. Images were analyzed using a voxelwise statistical test to detect reduction of brain parenchyma. In addition, an atlas-based volumetric study for regions likely to be affected by CD was performed.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adre-nocorticotropic hormone (median 17.5 pmol/L), cortisol (949.4 nmol/L), and dehydroepiandrosterone sulfate (5.4 μmol/L). The following values are expressed as the mean ± SD. The voxelwise statistical test revealed clusters of significantly reduced gray matter in the hippocampus and cerebellum, with volumes of 2.90 ± 0.26 ml (right hippocampus), 2.89 ± 0.28 ml (left hippocampus), 41.95 ± 4.67 ml (right cerebellar hemisphere), and 42.11 ± 4.59 ml (left cerebellar hemisphere). Healthy control volunteers showed volumes of 3.22 ± 0.25 ml for the right hippocampus, 3.23 ± 0.25 ml for the left hippocampus, 50.87 ± 4.23 ml for the right cerebellar hemisphere, and 50.42 ± 3.97 ml for the left cerebellar hemisphere.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Patients with untreated CD show significant reduction of gray matter in the cerebellum and hippocampus. These changes can be analyzed and objectified with the quantitative voxel-based method described in this study.</jats:p></jats:sec>

Moderating Effects of Cortisol on Neural-Cognitive Association in Cognitively Normal Elderly Subjects

“…The mean and standard deviation of serum cortisol levels were 32.34 ± 46.50 ng/mL (range = 7.95–305.77 ng/mL) in our samples, which is similar to the plasma cortisol levels reported in 95 healthy elderly men at 9 am (range = 38.48–329.10 ng/mL, age range 65–70 years old, MacLullich et al, 2005), and is much lower than the levels in Cushing’s disease patients (range = 147.05–829.31 ng/mL, Burkhardt et al, 2015). Details of the demographic data are reported in Table 1.…”

“…For instance, brain atrophy in bilateral hippocampal and cerebellar gray matter (GM) expressing high levels of glucocorticoid receptors (de Kloet et al, 2005; Hawrylycz et al, 2012) was observed in patients with uncontrolled Cushing’s disease, a state with high cortisol levels in the blood (Burkhardt et al, 2015). A recent meta-analysis showed that the damaging effect of high cortisol levels in Cushing’s syndrome on the human brain was irreversible (Andela et al, 2015).…”

Depression and Anxiety Scores Are Associated with Amygdala Volume in Cushing’s Syndrome: Preliminary Study

“…In fact, for the hippocampus a 10% increase has been demonstrated after disease remission [32]. Similar results have been found for the cerebellum, where smaller grey matter volumes were found in active patients compared to controls but did not differ when comparing with patients in remission [9, 13, 33]. …”

Volumetric magnetic resonance imaging analysis in patients with short‐term remission of Cushing's disease

“…However, these studies did not include segmentation of the white and grey matter. Accessing modern and more sophisticated analytical tools, three volumetric MR studies have yielded inconsistent results . Resmini et al …”

“…Accessing modern and more sophisticated analytical tools, three volumetric MR studies have yielded inconsistent results. 8,30,31 Resmini et al 30 found no differences in hippocampal volume between patients with active CS and HC, Andela et al 8 did not find alterations in the grey matter of hippocampus in patients with long-term remission CD. Two diffusion tensor-imaging studies demonstrated widespread reductions of white matter integrity in patients with CD.…”