Endocrine Abstracts (2017) 49 EP798 | DOI: 10.1530/endoabs.49.EP798

Dissecting the androgen excess phenotype of women with idiopathic intracranial hypertension

Michael O’Reilly1, Catherine Hornby1, Connar Westgate1, Hannah Botfield1, Keira Markey1, Carl Jenkinson1, Lorna Gilligan1, Mark Sherlock2, James Gibney2, Jeremy Tomlinson3, Wiebke Arlt1 & Alexandra Sinclair1

1University of Birmingham, Birmingham, UK; 2Tallaght Hospital and Trinity College, Dublin, Ireland; 3University of Oxford, Oxford, UK.

Abstract: Idiopathic intracranial hypertension (IIH) is a devastating neurological condition, with elevated intracranial pressure of unknown aetiology. IIH is largely a disease of obese females of reproductive age. The clinical phenotype of IIH overlaps with polycystic ovary syndrome (PCOS), with prevalent obesity, hyperandrogenism and anovulation. In this study, we aimed to delineate the androgen excess phenotype of IIH women compared to those with PCOS and simple obesity. Women with IIH (n=70), alongside age- and BMI-matched cohorts with PCOS (n=60) and simple obesity (n=40), were recruited to an in vivo study. Serum classic and 11-oxygenated androgens were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and urinary steroid excretion by gas chromatography-mass spectrometry. Cerebrospinal fluid (CSF) androgens were quantified by LC-MS/MS in IIH women (n=49) and a female cohort with non-IIH neurological disease (n=30). PCOS patients had increased insulin resistance, as measured by HOMA-IR (P<0.05), while HOMA-IR in IIH and controls did not differ. Serum testosterone was higher in IIH compared to both PCOS and control women (P<0.001 for both); conversely, serum androstenedione was higher in PCOS women than in IIH (P<0.001) and controls (P<0.01). Serum levels of the 11-oxygenated androgen precursors 11β-hydroxyandrostenedione and 11-ketoandrostenedione were increased in PCOS (P<0.0001), while levels in IIH patients did not differ from controls. Systemic 5α-reductase activity, as measured by the ratio of 5α-tetrahydrocortisol/tetrahydrocortisol, was higher in IIH women compared to both PCOS and controls (P<0.05 for both). IIH women had increased CSF androstenedione and testosterone compared to controls (all P<0.0001). Using mass spectrometry-based analysis, we show that women with IIH have a distinct androgen excess phenotype compared to PCOS and simple obesity, with higher active serum androgens, 5α-reductase activity and increased CSF androgens. Further studies are needed to understand the role of androgen excess in the pathogenesis of IIH.