Document Detail

Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients with idiopathic intracranial hypertension: a link between 11beta-HSD1 and intracranial pressure regulation?
MedLine Citation:
PMID:  20826586     Owner:  NLM     Status:  MEDLINE    
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.
Alexandra J Sinclair; Elizabeth A Walker; Michael A Burdon; Andre P van Beek; Ido P Kema; Beverly A Hughes; Philip I Murray; Peter G Nightingale; Paul M Stewart; Saaeha Rauz; Jeremy W Tomlinson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-08
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  2011-01-14     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5348-56     Citation Subset:  AIM; IM    
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MeSH Terms
11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors,  metabolism*
Adrenal Cortex Hormones / blood,  cerebrospinal fluid*,  urine
Biological Markers / cerebrospinal fluid,  metabolism
Choroid Plexus / pathology,  physiopathology
Chromatography, Liquid
Epithelial Cells / pathology
Gas Chromatography-Mass Spectrometry
Hydrocortisone / blood,  cerebrospinal fluid,  metabolism*
Intracranial Hypertension / complications,  metabolism,  physiopathology*
Intracranial Pressure / physiology*
Mass Spectrometry
Obesity / blood,  cerebrospinal fluid,  complications,  urine
Polymerase Chain Reaction
RNA / genetics,  isolation & purification
RNA, Messenger / genetics
Steroids / urine
Weight Loss
Grant Support
G0601430//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Biological Markers; 0/RNA, Messenger; 0/Steroids; 63231-63-0/RNA; EC Dehydrogenase Type 1; WI4X0X7BPJ/Hydrocortisone

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