Endocrine Abstracts

Background: Gaining a correct genetic diagnosis for patients with adrenal insufficiency is important not only to enable genetic counselling within their families, but also for correct treatment and long term management. Adrenal insufficiency is genetically heterogeneous and the long-term sequelae for many of the gene defects, including the progression of the disease and involvement of other tissues, is unknown. Next-generation sequencing (NGS) technologies allow parallel seque...

Glucocorticoids (GCs) are steroid hormones used to treat inflammatory diseases such as rheumatoid arthritis, but their clinical efficacy is hampered by development of side effects such as impaired wound healing. GCs bind the glucocorticoid receptor (GR) to mediate cellular effects. The inactive GR is held in multi-protein complex in the cytoplasm and upon ligand binding undergoes a conformational change, interacts with cytoplasmic enzymes to mediate non-genomic effects (within...

Chronic wounds contribute significantly to patient morbidity, mortality and associated healthcare costs. Glucocorticoid (GC) excess and hypoxia are both associated with impaired wound healing (WH) outcomes. The cyclooxygerase 2 (COX2) pathway is an integral component of inflammation and WH. Locally, GC availability is regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which generates cortisol from inactive cortisone. Although we recently demon...

Introduction: Adrenocortical carcinoma (ACC) is an aggressive malignancy with a high rate of recurrence. Regular post-operative follow-up imaging is necessary, but associated with high radiation exposure and frequent diagnostic ambiguity. Urine steroid metabolomics has recently been introduced as a novel diagnostic tool for the detection of adrenocortical malignancy in patients with adrenal incidentalomas. Here we present the first clinical study assessing the performance of t...

Endogenous glucocorticoids are secreted in hourly pulses, establishing a characteristic ultradian rhythm. Accordingly, the glucocorticoid receptor (GR) is activated in distinct pulses, causing target-gene pulsing. In contrast, constant glucocorticoid treatment causes aberrant target-gene overexpression in cell culture models, however this has not yet been described in vivo. Therefore, here we assess the effect of altering the glucocorticoid ultradian pattern on transc...

Steroid hormones and bile acids are potent regulators of metabolic phenotype. The enzyme 5β-reductase (AKR1D1) has a crucial role in bile acid synthesis and also generates 5β-reduced dihydrosteroid metabolites, regulating intra-cellular steroid availability though the clearance of cortisol, testosterone, androstenedione, and progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid metabolism, we have hypothesised that it plays a key role in me...