SFEBES2017 Poster Presentations Obesity and Metabolism (31 abstracts)
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.