Cerebrospinal fluid corticosteroid levels and cortisol metabolism in patients with idiopathic intracranial hypertension: a link between 11β-HSD1 and intracranial …
AJ Sinclair, EA Walker, MA Burdon… - The Journal of …, 2010 - academic.oup.com
The Journal of Clinical Endocrinology & Metabolism, 2010•academic.oup.com
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 …
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 …
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.
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