title: Hippocampal dysfunction in cured Cushing's syndrome patients, detected by (1) H-MR-spectroscopy.
abstract: BACKGROUND
  Proton magnetic resonance spectroscopy ((1) H-MRS) is a sensitive, noninvasive imaging technique capable of measuring brain metabolites in vivo. Chronic exposure to endogenous hypercortisolism in Cushing's syndrome (CS) is associated with negative effects on memory and hippocampal volumes, even after biochemical cure.
  
  
  OBJECTIVE
  To investigate metabolites in the hippocampi of CS patients and controls, using (1) H-MRS.
  
  
  METHODS
  Eighteen right-handed cured CS patients (age 44·8 ± 12·5 years, 12·6 ± 3·8 years of education) and 18 right-handed healthy controls, matched for age (40·0 ± 11·9) and years of education (14·4 ± 3·8), underwent 3-Tesla magnetic resonance imaging (3T MRI) and (1) H-MRS including the head of each hippocampus. Concentrations of Glu (Glutamate), Glx (Glutamate + Glutamine), NAA (N-Acetyl-aspartate), total NAA (N-Acetyl-aspartate + N-Acetyl-aspartyl-Glutamate), Cho (Glycerophosphocholine and Phosphocholine compounds), Cr (Creatine) and MI (mionositol) were measured (mmol/l). Hippocampal volumes (mm(3) ) were additionally calculated using an automated procedure (FreeSurfer).
  
  
  RESULTS
  CS patients had lower NAA than controls in the left and right hippocampus (5·2 ± 1·0 vs 6·1 ± 0·7, P < 0·05; 4·9 ± 0·8 vs 6·1 ± 0·6, P < 0·001, respectively), and lower total NAA on the right side (5·7 ± 0·9 vs 6·3 ± 0·9, P < 0·05), suggesting neuronal dysfunction/loss. CS patients had higher Glx than controls in both hippocampi (10·4 ± 1·9 vs 8·6 ± 1·4, P < 0·01; 9·9 ± 1·6 vs 8·9 ± 1·3, P < 0·05, respectively), suggesting glial proliferation, as a repair mechanism after neuronal dysfunction. No differences were found in the other brain metabolites, and there were no differences in left (3815·78 ± 502·96) and right (3980·75 ± 369·44) total hippocampal volumes between CS patients and controls (3945·08 ± 408·90 and 4108·39 ± 365·11, respectively).
  
  
  CONCLUSIONS
  Persistently abnormal metabolites are evidenced in the hippocampi of CS patients despite endocrine cure. These functional alterations could be early markers of glucocorticoid neurotoxicity, preceding hippocampal volume reduction.
authors.affiliation: Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Resmini
authors.forename: Alicia
authors.initials: A
authors.lastname: Santos
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gómez-Anson
authors.forename: Olga
authors.initials: O
authors.lastname: López-Mourelo
authors.forename: Patricia
authors.initials: P
authors.lastname: Pires
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vives-Gilabert
authors.forename: Iris
authors.initials: I
authors.lastname: Crespo
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Portella
authors.forename: Manel
authors.initials: M
authors.lastname: de Juan-Delago
authors.forename: Susan M
authors.initials: SM
authors.lastname: Webb
mesh_terms: D000328:Adult; D003480:Cushing Syndrome / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged