Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients with idiopathic intracranial hypertension: a link between 11beta-HSD1 and intracranial pressure regulation?

J Clin Endocrinol Metab. 2010 Dec;95(12):5348-56. doi: 10.1210/jc.2010-0729. Epub 2010 Sep 8.


Context: 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.

Design and setting: We conducted in vitro analysis of CP and AGT and a prospective in vivo cohort study set in two tertiary care centers.

Patients or other participants: Twenty-five obese adult female patients with active IIH were studied, and 22 completed the study.

Intervention: Fasted serum, CSF, and 24-h urine samples were collected at baseline, after 3-month observation, and after a 3-month diet.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism*
  • Adrenal Cortex Hormones / blood
  • Adrenal Cortex Hormones / cerebrospinal fluid*
  • Adrenal Cortex Hormones / urine
  • Adult
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Choroid Plexus / pathology
  • Choroid Plexus / physiopathology
  • Chromatography, Liquid
  • Epithelial Cells / pathology
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / cerebrospinal fluid
  • Hydrocortisone / metabolism*
  • Intracranial Hypertension / complications
  • Intracranial Hypertension / metabolism
  • Intracranial Hypertension / physiopathology*
  • Intracranial Pressure / physiology*
  • Mass Spectrometry
  • Obesity / blood
  • Obesity / cerebrospinal fluid
  • Obesity / complications
  • Obesity / urine
  • Polymerase Chain Reaction
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / genetics
  • Steroids / urine
  • Weight Loss


  • Adrenal Cortex Hormones
  • Biomarkers
  • RNA, Messenger
  • Steroids
  • RNA
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Hydrocortisone