Endocrine Abstracts

Introduction: The initial clinical trials for teprotumumab excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose > 1gm), or biologic treatment. Therefore, information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED.Methods: This is a multicenter retrospective study of all patients t...

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)....

Objectives: The insulin-like growth factor I receptor (IGF-1R) plays a significant role in the pathology of thyroid eye disease (TED), an autoimmune disorder characterized by orbital inflammation. Teprotumumab, a human monoclonal antibody targeting IGF-1R, has demonstrated efficacy in treating moderate-to-severe TED. A significant proportion of patients experienced adverse events (AEs), with 74% and 85% reporting an AE and 12% and 5% reporting serious AEs in Phase 2 and 3 tria...

The establishment of pregnancy requires dynamic remodelling of the endometrium. Decidualization, a key part of this process, is characterised by differentiation of endometrial stromal fibroblasts (ESF) which secrete factors that regulate implantation and placental development. We recently discovered that ESF synthesise androgens which modulate the expression of endometrial receptivity and decidualization markers. Utilisation of the circulating androgen precursor DHEA within ta...

In women, establishment of pregnancy is dependent upon ‘fine-tuning’ of the endometrial microenvironment which is mediated by differentiation (decidualisation) of human endometrial stromal fibroblasts (hESF). Using a robust in vitro model of decidualisation we have demonstrated an important role for local steroid metabolism in regulating hESF, something previously considered a solely endocrine-mediated process. We have conducted detailed time-course profilin...

Thyroid hormone is critically important for many developmental processes. However, less is known about how this hormone elicits its actions, a question that becomes more puzzling given that that distinct target tissues respond in different ways and often at different times. How does this systemic hormonal signal elicit its diverse responses? Targeted mutagenesis of thyroid hormone receptors (TR) encoded by the Thrb and Thra genes has indicated that some specifici...

There have always been conversations between clinicians about management and potential referral of patients, predominately from primary care to specialists. This has been called variously ‘advice and guidance (A&G)’, ‘specialist advice’ or ‘advice and refer’ by NHS England (NHSE). In the last few years, A&G has become increasingly relevant with escalating clinic pressures and is now part of the NHSE/GIRFT ‘elective care recovery and t...

Central dopamine and oxytocin have been shown in many studies to facilitate aspects of male sexual function. However, it is poorly understood how these two neuromodulators interact to mediate sexual behaviour or which receptors are involved. Much evidence has recently implicated a role for the dopamine D2 receptor in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in regulating aspects of male sexual behaviour. Using Sprague-Dawley male rats (225–250 g), we...

Oxytocin drives parturition by contracting the uterus, but transgenic mice with no oxytocin appear to give birth normally. We have previously shown that oxytocin antagonist administration delays births showing that oxytocin plays a role in normal mouse parturition. Here, we tested the hypothesis that oxytocin neurones are active during parturition, using double immunocytochemistry for Fos and oxytocin to show neuronal activation and radioimmunoassay of blood samples to seek in...