Endocrine Abstracts

Synthetic glucocorticoids bind to the glucocorticoid receptor (GR) and have been used for nearly 70 years to treat inflammatory diseases. However, their use is limited by adverse effects such as diabetes, muscle wasting and osteoporosis. High throughput screening identified a novel non-steroidal scaffold with great potential for chemical optimization. Through rational design we developed the indazole ether series which combines high potency with structural motifs that provide ...

Introduction: Hypothalamic amenorrhoea (HA) is a condition characterised by reduced GnRH pulsatility and is a common cause of anovulatory subfertility. Kisspeptin is an endogenous neuropeptide that regulates hypothalamic GnRH function. Hypothalamic kisspeptin expression is reduced, and kisspeptin receptor expression is increased, in a rodent model of HA. The kisspeptin analogue MVT-602 has a 3-4-fold longer half-life than native kisspeptin-54 (t1/2 0.5 h). We invest...

Background: Primary adrenal insufficiency (PAI) predisposes patients to infections, which can precipitate life-threatening adrenal crises. PAI patients are thought to be particularly vulnerable to COVID-19; however, little is known about its true impact on this group.Aim: To assess morbidity and health promotion attitudes during the COVID-19 pandemic amongst a large cohort of PAI patients.Methods: In May 2020 COVID-19 information, ...

Background: The incidence of adrenal crisis remains constant, despite the introduction of behavioural interventions to educate and empower patients. To increase the success of future behaviour change interventions, theoretically informed and empirically supported behaviour change frameworks are available. The current review aimed to identify and evaluate available evidence of interventions used to prevent adrenal crisis in people with primary adrenal insufficiency to inform fu...

Background: Behavioural interventions have been developed to empower patients with adrenal insufficiency and prevent adrenal crisis. Behavioural theory, such as the theoretical domains framework, can inform future intervention development. The current systematic review aims to describe what techniques have been employed in previous interventions and highlight neglected behavioural barriers that could be targeted in future interventions.Methods: We perfor...

Background: Peptide receptor radionuclide therapy (PRRT) is based on tumor somatostatin receptor (SSR) overexpression to deliver targeted isotope therapy. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy, but there is no method to objectively predict PRRT efficacy. We report the efficacy of Predictive Quotient Index (PQI) to predict the utility of PPRT. PQI is derived from circulating NET transcript analysis (NETest) integrated with the tu...

Background: Islet transplant into the liver is a therapy for type 1 diabetes patients experiencing severe hypoglycaemia or impaired hypoglycaemic awareness. Widespread use is not currently considered due to the requirement for immunosuppression for the lifetime of the graft, and the attrition in graft function over the following 1-5 years. Following transplant into the liver, inflammation results in >60% islet loss, with few patients achieving insulin independence. The liv...

Allan-Herndon-Dudley syndrome (AHDS) is a genetic disorder characterized by intellectual disability and movement disorders. AHDS patients have mutations in the monocarboxylate transporter 8 (MCT8) that impedes thyroid hormone (TH) transport to the brain during crucial phases of brain development. In mice, the resulting structural and functional pathologies of human AHDS patients can be mimicked by knocking out murine MCT8 and the Solute Carrier Organic Anion Transporter Family...

Secondary hormonal deficiency (SHD) is common in patients presenting with nonfunctioning pituitary adenomas (NFA). NFA can either stain for various hormones or be non-hormone staining on immunocytochemistry. To date, no study has assessed the association between staining pattern of NFA and pattern of SHD at presentation. The Halifax Neuropituitary Program has been prospectively collecting comprehensive data on all neuropituitary patients in the province of Nova Scotia, Canada ...

Objectives: Despite the introduction of new molecular targeted therapies, there is still an unmet need for an effective systemic therapy for advanced medullary thyroid carcinoma (MTC). As MTC expresses cholecystokinine-2 (CCK-2) receptors at a high incidence and density, targeting the CCK-2 receptor with radiolabelled gastrin analogues is a potential approach for radionuclide therapy. Unfortunately, kidney and bone marrow toxicity precluded therapeutic applications of CCK-2 re...