Endocrine Abstracts

A tightly regulated stress system is pivotal for health and the adrenal cortex is a master regulator of the endocrine stress response. The adrenal cortex is characterized by constant cell renewal in part mediated by differentiation and lineage conversion of undifferentiated cell types. To date, the contribution of stem cells to organ plasticity during stress has been implicated but is not fully understood. Recently, we were able to show that a prolonged stress exposure leads t...

ContextPrenatal dexamethasone (Dex) therapy is used in female foetuses with congenital adrenal hyperplasia (CAH) to suppress adrenal androgen excess and prevent virilisation of the external genitalia. The prenatal dexamethasone dose of 20 µg/kg per day has been used for decades in prenatal CAH and is associated with risks for the treated mother and potentially for the unborn child. Despite the high medical need, no prospective, clinical studies had ...

Prostate Cancer (PC) affects 1-in-6 men in the UK, and obesity 1-in-3, with rates of both increasing. High-fat diet is linked with increased risk of PC death, and volume of peri-prostatic adipose tissue (PPAT) is associated with increased risk of lethal PC/reduced therapy response. Despite this, molecular mechanisms underpinning obesity-driven PC remain poorly-understood. This is important since weight-gain and central obesity are major side-effects of PC trea...

Self-limited delayed puberty is a condition that is frequently familial with strong genetic determinants. It has been linked to coding region sequence variation by next generation sequencing of affected individuals, identifying genetic regulation of gonadotropin-releasing hormone (GnRH) pathways underlying this condition. However, the role of epigenetic modifiers of human pubertal timing is underexplored. The Hypothalamic-pituitary-gonadal (HPG) axis is unique as it is active ...

Background: Cut-offs for basal cortisol (early morning) have been determined to predict the 30-minute cortisol level post-synacthen, but not for determining when patients with suspected tertiary adrenal insufficiency (AI) are weaned off glucocorticoids.Aims: The aim of this study was to compare the predictive values of basal cortisol, basal ACTH and basal cortisol:ACTH ratio to determine appropriate thresholds to reduce ...

Adrenocortical carcinoma (ACC) is a rare tumour with a poor prognosis. There are a lack of successful targeted therapies and an urgent need to explore novel therapeutic avenues for ACC 1. In other cancer types, there has been some success in exploiting lipid metabolism. One example is manipulating intracellular cholesterol levels to starve cancer cells. 2 Another possibility is targeting the ligand-dependent nuclear receptors Liver-X receptors (LXRab), wh...

The General Medical Council’s publication ‘Outcomes for Graduates’ places emphasis on doctors being able to integrate biomedical science, research, and scholarship with clinical practice. In response, a new paradigm of assessment was introduced for the intercalated Bachelor of Science (iBSc) in Endocrinology program at Imperial College School of Medicine. The approach involves authentic “active learning” assessments analogous to tasks encountered in a ...

Background: The current screening test for adrenal insufficiency (AI) involves patients attending hospital for an “early” morning serum cortisol sample, generally taken some considerable time after the child has woken. This risks missing the morning cortisol peak, leading to false positive results. It requires venepuncture, which is unpleasant for children. Saliva collection is non-invasive, simple and can be undertaken on waking at home, providing a...

Background: 5-Hydroxyindoleacetic acid (5-HIAA) is the main metabolite of serotonin and is measured in all patients newly diagnosed with neuroendocrine tumours both to diagnose carcinoid syndrome and to monitor treatment response for those with an elevated baseline level. Each test requires patients to avoid certain foods and collect urine over a 24 hour period. It is not known to what extent patients adhere to these requirements or find them burdensome. There...

Liver X receptors (LXRs) are are ligand-dependent transcription factors, members of the nuclear receptor superfamily of transcription factors. In humans two LXR isoforms exist, LXRα (NR1H3) and LXRβ (NR1H2). LXRα is expressed predominantly in metabolically active tissues, while LXRβ is expressed in the majority of tissues. They have long been known to have critical roles in regulation of lipid metabolism, particu...