Endocrine Abstracts

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 w...

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. Wo...

In patients with autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion; patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Recent early-phase studieshave demonstrated that some endogenous steroidogenic function – Residual Adrenal Function (RAF) - is maintained at the point of diagnosis in a proportion of AAD patients; this...

Active androgens exert immunomodulatory actions at sites of inflammation and lower levels are implicated in the increased incidence of rheumatoid arthritis (RA) in females. However, inflammatory regulation of intracrine androgen metabolism within cell populations at sites of inflammation remain poorly defined. In this study we characterised immune and stromal cell androgen metabolism in RA patients and assessed their functional significance. Using the online Accelerating Medic...

Introduction: Gas chromatography mass spectrometry (GC-MS) is the gold standard method for urinary steroid profiling. However, GC-MS requires chemical derivatisation, long run times, is labour intensive, expensive, and unsuitable for rapid multi-sample analysis, limiting its use in routine clinical practice. GC-MS urinary steroid metabolomics, the combination of steroid profiling and machine learning (Generalized Matrix Learning Vector Quantization) was shown to have superior ...

Polycystic ovary syndrome (PCOS) affects 10% of women and is associated with an increased risk of type 2 diabetes and fatty liver disease. Androgen excess is an important driver of metabolic risk in PCOS. In adipose tissue from women with PCOS, increased activation of androstenedione (A4) to testosterone (T) by the enzyme AKR1C3 results in systemic lipotoxicity. Recent in-vitro studies also demonstrated that T and 11-ketotestosterone (11KT) activate the androgen recep...

Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with dysregulated glucocorticoid metabolism. Advanced stages of NAFLD are associated with adverse outcome and current strategies to stage disease severity are still reliant upon liver biopsy. We have previously described changes to enzymatic pathways that regulate cortisol bioavailability; 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1) regenerates cortisol from inactive cortisone, and A-ring re...

Context: Cytochrome P450 (CYP) 17A1 is located at major branch points of steroidogenesis exerting two distinct catalytic activities: 17α-hydroxylase generates glucocorticoid precursors and 17,20-lyase generates the principal sex steroid precursor dehydroepiandrosterone (DHEA). CYP17A1 deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. In severe 17OHD, affected individuals typically present with both glucocorticoid and sex steroid deficiency and mineraloc...

Clinical vignette: We investigated a 33-year-old woman diagnosed during pregnancy with a 7cm unilateral adrenal mass associated with severe ACTH-independent glucocorticoid and androgen excess, a steroid phenotype usually indicative of adrenocortical carcinoma. Pregnancy had been achieved with in-vitro fertilisation on the assumption of underlying PCOS. Neonatal death occurred soon after emergency delivery due to foetal growth arrest at 26 weeks gestation. Hist...

Background: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome. Primary unilateral macronodular adrenal hyperplasia with concomitant glucocorticoid and androgen excess has never been studied before.Methods: We investigated a woman with a large, heterogeneous 7 cm adrenal mass (with a radiologically normal contralateral adrenal) and adrenocorticotropic hormone (ACTH)-independent glucocorticoid and androge...