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Background The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). Methods We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. Results Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P < .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. Conclusions These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.

Louise S Roper,1–3 Peter Nightingale,4 Zhangjie Su,5,6 James L Mitchell,1–3 Antonio Belli,5,6 Alexandra J Sinclair1–3 1Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, 2Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, 3Department of Neurology, 4Wolfson Computer Laboratory, University Hospital Birmingham NHS Foundation Trust, 5Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, 6Health Research Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK Background: Posttraumatic headache (PTH) occurs in up to 82% of patients with traumatic brain injury (TBI). Posttraumatic stress disorder (PTSD) occurs in 39% of those with PTH. This study evaluates whether PTSD affects PTH disability. Methods: Eighty-six patients with TBI were prospectively evaluated in a secondary care trauma center. Headache disability was assessed using the Headache Impact Test version 6 and signs indicative of PTSD using the PTSD Check List Civilian version. Results: Increased PTSD-type symptoms were significantly associated with increased headache disability (p