Endocrine Abstracts

Introduction: The 250µg Short Synacthen test (SST) is the reference standard for a diagnosis of adrenal insufficiency (AI) in most endocrine centres. The test is expensive and time consuming, requiring clinic attendance. We hypothesised that a cheaper home waking salivary cortisone (WSC) is predictive of the SST 30-minute cortisol >430 nmol/l cut-off and carried out a diagnostic accuracy study to assess the predictive value of the WSC in diagnosing and excluding AI. W...

Primary hyperparathyroidism (PHP), usually due to multigland hyperplasia, occurs in >90% of patients with multiple endocrine neoplasia type 1 (MEN1). The literature is divided on the optimal surgical management for such patients. We report a retrospective cohort study on the long-term outcomes associated with limited, subtotal, or total parathyroidectomy as initial surgery for PHP in MEN1. The primary endpoint was recurrent PHP defined as an adjusted serum calcium >2.6 mmol/l ...

Endocrine Society guidelines recommend random growth hormone (RGH) <1 mcg/l as indicative of biochemical control of acromegaly. Growth hormone (GH) control may also be determined using the mean GH (MGH) of a growth hormone day curve (GHDC). We report a retrospective analysis of 461 consecutive GHDCs, from 121 patients with treated acromegaly, performed in a single centre between 2009 and 2019. Each GHDC contained 7–9 GH measurements (mean 8.9) taken at regular interva...

Promiscuous multi-agonists that simultaneously activate two or three key receptors (incretin- and/or glucagon receptor) were recently shown to improve glycemic control in mice. Here we investigated the underlying mechanisms of multi-agonists to enhance insulin secretion in murine islets and human pancreatic β-cells. These mixed agonists display a greater potency in cAMP signaling as compared to the native incretins. However, pharmacological blockade of cAMP signaling only...

The anti-fibrotic, vasodilatory, and angiogenic therapeutic properties of relaxin peptide have been shown in several animal models of human diseases and in clinical trials. Using high-throughput screening of small molecule library, structure-activity relationship (SAR) studies, ligand-receptor interaction modeling, site-specific mutagenesis, and transgenic animal studies we discovered the first series of small molecule agonists of relaxin GPCR, RXFP1. The lead compound ML290 i...

Androgen Receptor (AR) is central to prostate cancer (PCa) tumorigenesis and metastases. The genomic actions of androgens are mediated by the AR in complex with multiple chromatin modifying coregulators. We and others have identified lysine demethylases (KDMs) as important mediators of androgen signaling and increased expression of specific coregulators, including KDM1A, are implicated in PCa recurrence. There is an urgent need for new PCa treatments. While androgen deprivatio...

Introduction: Fine needle aspiration cytology (FNAC) is a widely adopted pre-operative investigatory tool for thyroid nodules. The British Thyroid Association (BTA) recently updated guidelines recommending that an FNAC that initially yields benign cytology (Thy2) should be repeated if there is any clinical or ultrasound (US) suspicion (1). We postulate that there is a tendency for a more conservative approach in older age groups with smaller thyroid nodules on US studies.<...

Introduction: Worldwide the Short Synacthen Test (SST) is the most popular investigation for adrenal insufficiency (AI). Its invasivity make it resource-intensive. Salivary cortisol is a well-established alternative to serum. We have developed a non-invasive alternative to the SST, using a novel formulation of Synacthen (containing a drug enhancer, chitosan) administered nasally and utilising saliva to measure glucocorticoid response.Methods: Four open-l...

The study of humans carrying dominant negative mutations in PPAR gamma has contributed significantly to our understanding of its role in human physiology. To date, comparable studies of PPAR alpha have not been reported. Using a pooled approach, we undertook exon sequencing of PPARA in 11,848 adult participants of the Fenland study, a population-based cohort study with detailed metabolic phenotyping. Twenty-nine PPARA missense variants were detected (allelic ...

Activation of complement factor 5 (C5) produces the anaphylatoxin C5a and the proinflammatory cytolytic complex C5b-9. Recent studies have shown that C5a receptor (C5aR) deficiency leads to improved systemic and white adipose tissue (WAT) insulin sensitivity. This phenotype is considered to be due to the potent inflammatory potential of signalling through C5aR; however, the pleiotropic functions of C5 in inflammation and metabolism remain to be elucidated. We investigated the ...