Endocrine Abstracts

Introduction: Barrett’s esophagus is metaplasia in the cells of the lower end of the esophagus. It is characterized by the replacement of the normal stratified squamous epithelium lining of the esophagus by simple columnar epithelium with goblet cells. The disease is often related to gastroesophageal reflux and patients have pain necessitating chronic usage of proton pump inhibitors. Proton pump inhibitors have been associated with the development of low bone mineral dens...

Purpose: IGF-1R antagonism reduces TED-related inflammation and proptosis. VRDN-001, a subnanomolar affinity full antagonist antibody to IGF-1R, is being evaluated in a phase 1/2 RCT (NCT05176639) at 3-20 mg/kg. We present results from the first cohort (10 mg/kg) of TED patients.Methods: Adults with active moderate-to-severe TED with clinical activity score (CAS) ≥4 were randomized to 2 infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo...

Objectives: Antagonism of the IGF-1 receptor (IGF-1R) has been shown to reduce TED-related inflammation and proptosis. VRDN-001, a high-affinity antagonist antibody to IGF-1R, has distinct pharmacological properties that may enable differentiated dosing and better efficacy than observed with other antibodies. We assessed VRDN-001 in vitro pharmacology compared with teprotumumab and clinical proof of concept in a phase 1/2 randomized controlled trial (NCT05176639)....

Background: Wolfram Syndrome (WS) is a rare autosomal recessive disorder characterised by early-onset diabetes and optic atrophy as well as a variable spectrum of other endocrine and neurological conditions. It is caused by mutations in the WFS1 gene. Previous reports have documented a variable prevalence of hypogonadism (6.3% of the international EURO-WABB registry, 34% of a German cohort); however the only UK cohort reported was of 10 males, 7 of whom had primary gonadal atr...

Background: HSD-1 converts cortisone to cortisol in tissues in which cortisol excess is associated with morbidity including liver, adipose, bone, and brain. SPI-62 is a potent HSD-1 inhibitor in clinical development for treatment of Cushing’s syndrome and autonomous cortisol secretion, and as adjunctive therapy to prednisolone in polymyalgia rheumatica. In Phase 1 clinical trials SPI-62 was generally well tolerated and associated with maximal liver and brain HSD-1 inhibit...

It is over 17 years since the randomised controlled trial of metformin showed efficacy in childhood type 2 diabetes. Since that time, despite much investment in paediatric investigation plans, very few interventional clinical trials have reported. This presentation reviews the evidence for childhood type 2 diabetes being different to adult type 2 diabetes. Childhood type 2 diabetes is a more aggressive disease; children have lower insulin sensitivity than adults; and complicat...

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Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders of young women, and the commonest cause of reduced fertility in this age group. There are fundamental metabolic disturbances integral to the syndrome that lead to significant cardiovascular risk, and these include obesity, insulin resistance, beta cell dysfunction, impaired glucose tolerance and type 2 diabetes, dyslipidemia, hypertension, obstructive sleep apnoea, a pro-coagulant state, and endothe...

Background: Paediatric emergency departments saw an unusual increased incidence and severity of DKA in children with new onset diabetes in the COVID pandemic. The DIMPLES study (Diabetes Mellitus in children and young people presenting to the Emergency Department during the SARS-CoV-2 pandemic) explored this using retrospective multicentre data from 49 EDs, providing a unique perspective of paediatric diabetes from the frontline.Methods: We compared the ...

For >50 years female cardioprotection was attributed to premenopausal endogenous estrogen levels. We describe here how cardioprotection is greatly reduced in the presence of diabetes and endogenous testosterone levels.Forty years ago we measured total and bioavailable testosterone (bioT), total and bioavailable estradiol, and SHBG in community-dwelling older men and women from the Rancho Bernardo Study, using organic solvent extraction and celite col...