Hippocampal and cerebellar atrophy in patients with Cushing's disease

Neurosurg Focus. 2015 Nov;39(5):E5. doi: 10.3171/2015.8.FOCUS15324.


OBJECT 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. METHODS 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. RESULTS Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adrenocorticotropic 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. CONCLUSIONS 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.

Keywords: ACTH = adrenocorticotropic hormone; CD = Cushing’s disease; CS = Cushing’s syndrome; Cushing’s disease; DHEA-S = dehydroepiandrosterone sulfate; GM = gray matter; MNI = Montreal Neurological Institute; MPRAGE = magnetization-prepared rapid gradient echo; TIV = total intracranial volume; VBM = voxel-based morphometry; WM = white matter; atrophy; cerebellum; hippocampus.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Aged
  • Atrophy / metabolism
  • Atrophy / pathology
  • Cerebellum / metabolism
  • Cerebellum / pathology*
  • Dehydroepiandrosterone Sulfate / blood
  • Female
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Humans
  • Hydrocortisone / blood
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Pituitary ACTH Hypersecretion / blood
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Prospective Studies
  • Young Adult


  • Dehydroepiandrosterone Sulfate
  • Adrenocorticotropic Hormone
  • Hydrocortisone