Endocrine Abstracts

Zoledronate in the Prevention of Paget’s disease (ZiPP) trial (ClinicalTrials.gov ID:NCT03859895) is a multi-centre, double-blind, placebo-controlled, randomised trial of Zoledronic acid (ZA) in sequestosome1 (SQSTM1) mutation carriers. SQSTM1 mutation has high penetrance and is associated with the early onset of Paget’s disease of bone. Participants with the SQSTM1 genotype received either a single dose of IV 5mg ZA (Aclasta, Novartis); intervention group n...

Background and Aims: Type 1 diabetes mellitus (T1DM) is characterised by autoimmune destruction of pancreatic beta-cells resulting in insulin deficiency. Evaluation of novel therapies for T1DM requires reliable methods to measure beta-cell function, which is unattainable using traditional non-invasive imaging techniques. A new approach is manganese-enhanced magnetic resonance imaging (MEMRI). As a calcium analogue, manganese is taken up into pancreatic beta-cells during insuli...

Hypomorphic CYP24A1 protein coding mutations causing inappropriate 1,25(OH)2D concentrations are associated with idiopathic infantile hypercalcemia and adult-onset hypercalciuria and nephrolithiasis. It is unclear why some cases present with CYP24A1-mediated abnormal calcium handling lack protein-coding CYP24A1 mutations. Non-coding region mutations, e.g. the 3’ UTR, impacting messenger RNA (mRNA) structure have rarely been studied in...

Genome-wide association studies have identified nearly 250 loci carrying genetic variants associated with type 2 diabetes (T2D) susceptibility, which are often located within pancreatic islet transcriptional enhancers. Due to the complex nature of transcriptional enhancers, assigning risk variants to true disease susceptibility effector genes has remained a challenge. In this study, we applied promoter capture Hi-C to create a genome-wide map of promoter-enhancer interactions ...

Background: High risk patients with differentiated thyroid cancer (DTC) undergoing radioiodine (I-131) treatment can be prepared by thyroid hormone withdrawal (THW) or with parenteral recombinant TSH (rhTSH). We compared two centres predominantly using THW or rhTSH to study the impact on radioiodine retention and length of hospital stay (LoHS).Methods: We retrospectively compared radioactivity at discharge following high dose I-131 therapy (3–5 GBq ...

Hypoparathyroidism, a rare disorder characterized by absent or low levels of parathyroid hormone (PTH), often results from thyroid surgery. However, nonsurgical etiologies are present in >10% of patients. Data about this group of patients are limited.In this post hoc REPLACE (NCT00732615, EudraCT2008-005063-34) analysis, baseline characteristics and response to 50–100 μg/day rhPTH(1-84) in patients with postsurgical or nonsurgical ...

Background: There is uncertainty regarding the selection of obese patients for metabolic procedures, how to define a successful outcome and pre-operative predictors of success. Our aim was to explore the influence of obesity on preoperative quality of life in patients awaiting bariatric surgery.Methods: Pre-operative data were accrued for morbidly obese patients (n=70) at the University Hospitals Coventry and Warwickshire (UHCW) during the last ...

Background: Pre-operative predictive measures of post-metabolic surgery success would facilitate a more refined evidence-based selection of patients. This study aimed at identifying those clinical and psycho-social predictors of success (defined as weight-loss) following metabolic surgery.Methods: Pre-operative data including IWQOL-Lite questionnaire (a validated self-reported 31-item measure of physical function, self-esteem, sexual life, public distres...

Heterozygous mutations of GATA3, a dual zinc-finger transcription factor, cause the hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome. To study the role of GATA3 in parathyroid function we have investigated Gata3+/− mice for hypoparathyroidism. Gata3+/− and Gata3+/+ mice were challenged at weaning with a diet low in calcium (0.001%) and vitamin D (0.0 IU/g). The low calcium-vitamin D diet led to a ...

Phaeochromocytomas (PHAEO)/paragangliomas (PGL) are neuro-endocrine tumours. They may present sporadically or as the primary abnormality in a number of familial syndromes. Advances in molecular genetics have led to the identification of several PHAEO/PGL predisposing genes including VHL, NF1 and RET. Mutations in the genes encoding the subunits of Succinate Dehydrogenase (SDH) have also been reported. We describe the phenotype of a cohort of patients with a Succinate Dehydroge...