title: Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients with idiopathic intracranial hypertension: a link between 11beta-HSD1 and intracranial pressure regulation?
abstract: BACKGROUND
  The etiology of idiopathic intracranial hypertension (IIH) is unknown. We hypothesized that obesity and elevated intracranial pressure may be linked through increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity.
  
  
  OBJECTIVE
  The aim was to characterize 11β-HSD1 in human cerebrospinal fluid (CSF) secretory [choroid plexus (CP)] and drainage [arachnoid granulation tissue (AGT)] structures, and to evaluate 11β-HSD1 activity after therapeutic weight loss in IIH.
  
  
  METHODS
  We conducted in vitro analysis of CP and AGT and a prospective in vivo cohort study set in two tertiary care centers.
  
  
  METHODS
  Twenty-five obese adult female patients with active IIH were studied, and 22 completed the study.
  
  
  METHODS
  Fasted serum, CSF, and 24-h urine samples were collected at baseline, after 3-month observation, and after a 3-month diet.
  
  
  METHODS
  Changes in urine, serum, and CSF glucocorticoids (measured by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry) after weight loss were measured.
  
  
  RESULTS
  11β-HSD1 and key elements of the glucocorticoid signaling pathway were expressed in CP and AGT. After weight loss (14.2±7.8 kg; P<0.001), global 11β-HSD1 activity decreased (P=0.001) and correlated with reduction in intracranial pressure (r=0.504; P=0.028). CSF and serum glucocorticoids remained stable, although the change in CSF cortisone levels correlated with weight loss (r=-0.512; P=0.018).
  
  
  CONCLUSIONS
  Therapeutic weight loss in IIH is associated with a reduction in global 11β-HSD1 activity. Elevated 11β-HSD1 may represent a pathogenic mechanism in IIH, potentially via manipulation of CSF dynamics at the CP and AGT. Although further clarification of the functional role of 11β-HSD1 in IIH is needed, our results suggest that 11β-HSD1 inhibition may have therapeutic potential in IIH.
authors.affiliation: Academic Unit of Ophthalmology, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham and Midland Eye Centre, Dudley Road, Birmingham B18 7QU, United Kingdom.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Sinclair
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Walker
authors.forename: Michael A
authors.initials: MA
authors.lastname: Burdon
authors.forename: Andre P
authors.initials: AP
authors.lastname: van Beek
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Hughes
authors.forename: Philip I
authors.initials: PI
authors.lastname: Murray
authors.forename: Peter G
authors.initials: PG
authors.lastname: Nightingale
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Saaeha
authors.initials: S
authors.lastname: Rauz
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Tomlinson
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000097:blood / Q000134:cerebrospinal fluid* / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D002831:Choroid Plexus / Q000473:pathology / Q000503:physiopathology; D002853:Chromatography, Liquid; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D019586:Intracranial Hypertension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000502:physiology*; D013058:Mass Spectrometry; D009765:Obesity / Q000097:blood / Q000134:cerebrospinal fluid / Q000150:complications / Q000652:urine; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D013256:Steroids / Q000652:urine; D015431:Weight Loss
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D012333:RNA, Messenger; D013256:Steroids; D012313:RNA; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone