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Context Idiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown aetiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism yet to be assessed. Objective To determine the basal glucocorticoid phenotype in IIH and assess the effects of weight loss on the IIH glucocorticoid phenotype. Design A retrospective case-control study and a separate exploratory analysis of a prospective randomised intervention study. Methods The case-control study compared female IIH patients to body mass index, age, and sex-matched controls. The randomised intervention study, different IIH patients were randomized to either a community weight management intervention, or bariatric surgery, with patients assessed at baseline and 12 months. Glucocorticoid levels were determined utilising 24-hour urinary steroid profiles alongside the measurement of adipose tissue 11β-HSD1 activity. Results Compared to control subjects, patients with active IIH had increased systemic 11β-hydroxysteroid dehydrogenase (11β-HSD1) and 5α-reductase activity. The intervention study demonstrated that weight loss following bariatric surgery reduced systemic 11β-HSD1 and 5α-reductase activity. Reductions in these were associated with reduced ICP. Subcutaneous adipose tissue explants demonstrated elevated 11β-HSD1 activity compared to samples from matched controls. Conclusion We demonstrate that in IIH, there is a phenotype of elevated systemic and adipose 11β-HSD1 activity in excess to that mediated by obesity. Bariatric surgery to induce weight loss was associated with reductions in 11β-HSD1 activity and decreased ICP. These data reflect new insights into the IIH phenotype and further point towards metabolic dysregulation as a feature of IIH.

Original publication




Journal article


Eur J Endocrinol

Publication Date