Obesity, 11β-hydroxysteroid dehydrogenase and metabolic changes in the pathogenesis of idiopathic intracranial hypertension

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http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/2529 http://eprints.org/relation/ispreviewThumbnailVersionOf http://etheses.bham.ac.uk/id/document/2529 http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/2529 archive 4031 disk0/00/00/10/13 2010-11-10 17:38:03 2019-01-23 09:53:19 2011-07-19 16:27:50 thesis show 0 Sinclair Alexandra Rauz Saaeha Walker Elizabeth Stewart Paul M Burdon Michael University of Birmingham Obesity, 11β-hydroxysteroid dehydrogenase and metabolic changes in the pathogenesis of idiopathic intracranial hypertension unpub RE R1 QP 10col_mede Idiopathic intracranial hypertension (IIH) is a blinding condition amongst the young obese female population characterised by elevated intracranial pressure (ICP). The aetiology of IIH is not known and, as highlighted in the 2005 Cochrane review, an evidence base for treatment has not been established, although weight loss is frequently advocated. Obesity is associated with dysregulation of cortisol metabolism by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Additionally, 11β-HSD1 has a role in the regulation of intraocular pressure. This thesis hypothesised that 11β-HSD1 is involved in the aetiology of IIH and examined the roles of obesity, 11β-HSD1 and metabolic changes in the pathogenesis and treatment of IIH. We demonstrated that ICP regulating structures (choroid plexus and arachnoid granulation tissue), are potential glucocorticoid target tissues expressing 11β-HSD1. Metabolomic analysis identified a unique biofluid metabolite biomarker profile, with potential implications for IIH pathogenesis. We established the therapeutic efficacy of weight loss in IIH (improving headaches, papilloedema and ICP) and provided evidence that the beneficial effects may relate to alterations in the glucocorticoid profile driving 11β-HSD1 and potentially, 5α reductase. These studies have started to address the important issues of causation and treatment in IIH and provide avenues for future research into this complex condition. 2010-07 2010-03 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. public 281 University of Birmingham School of Immunity and Infection d_ph na 2010-07 graduation