ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 50 P320 | DOI: 10.1530/endoabs.50.P320

Androgen excess is highly prevalent in women with idiopathic intracranial hypertension and is biochemically distinct from polycystic ovary syndromes

Michael O’Reilly1, Catherine Hornby1, Connar Westgate1, Hannah Botfield1, Keira Markey1, James Mitchell1, Carl Jenkinson1, Lorna Gilligan1, Mark Sherlock2, James Gibney2, Jeremy Tomlinson3, Wiebke Arlt1 & Alexandra Sinclair1

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

Idiopathic intracranial hypertension (IIH) is a condition of unknown aetiology characterised by raised intracranial pressure, chronic headaches and blindness. Akin to polycystic ovary syndrome (PCOS), IIH patients are almost exclusively obese females of reproductive age. A distinct androgen excess profile has been noted in PCOS. Here, we aimed to delineate androgen metabolism in IIH compared to 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. Comprehensive serum androgen profiling, including 11-oxygenated androgens recently shown to represent the major androgens in PCOS, was carried out by by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 24-h urine steroid profiling by gas chromatography-mass spectrometry in all three groups. In IIH women (n=49) and a female cohort with non-IIH neurological disease (n=30), we also quantified androgens in cerebrospinal fluid (CSF) utilising LC-MS/MS.

PCOS patients had increased insulin resistance, as measured by HOMA-IR (P<0.05), while HOMA-IR in IIH did not differ from controls. 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 significantly increased CSF androstenedione and testosterone compared to controls (all P<0.0001).

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 mechanistic role of androgen excess in the pathogenesis of IIH.