title: Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case-control study.
abstract: OBJECTIVE
  Patients with long-term remission of Cushing's disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction and clinical severity.
  
  
  METHODS
  A cross-sectional, case-control study.
  
  
  METHODS
  In 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, and anterior cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic resonance imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushing's syndrome severity index.
  
  
  RESULTS
  Compared with controls, patients had smaller grey matter volumes of areas in the ACC (on average 14%, P<0.05) and greater volume of the left posterior lobe of the cerebellum (on average 34%, P<0.05). As expected, patients with remitted CD reported more depressive symptoms (P=0.005), more anxiety (P=0.003), more social phobia (P=0.034), more apathy (P=0.002), and more cognitive failure (P=0.023) compared with controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity.
  
  
  CONCLUSIONS
  Patients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, C7-Q, Center for Endocrine Tumors, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Cornelie D
authors.initials: CD
authors.lastname: Andela
authors.forename: Steven J A
authors.initials: SJ
authors.lastname: van der Werff
authors.forename: J Nienke
authors.initials: JN
authors.lastname: Pannekoek
authors.forename: Susan M
authors.initials: SM
authors.lastname: van den Berg
authors.forename: Onno C
authors.initials: OC
authors.lastname: Meijer
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
authors.forename: Roos C
authors.initials: RC
authors.lastname: van der Mast
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Jitske
authors.initials: J
authors.lastname: Tiemensma
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: Nic J A
authors.initials: NJ
authors.lastname: van der Wee
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
mesh_terms: D000328:Adult; D001007:Anxiety / Q000209:etiology; D057565:Apathy; D016022:Case-Control Studies; D002531:Cerebellum / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000473:pathology / Q000523:psychology; D003863:Depression / Q000209:etiology; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology*; D009929:Organ Size; D010698:Phobic Disorders / Q000209:etiology; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000523:psychology* / Q000628:therapy; D010907:Pituitary Hormones / Q000097:blood; D012074:Remission Induction; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D010907:Pituitary Hormones; D006854:Hydrocortisone