Endocrine Abstracts

Transcription factors (TFs) regulate gene expression by interacting with chromatinized DNA response elements (REs). Access to these elements is dramatically restricted by chromatin organization, and modification of the nucleoprotein structure to allow factor binding is a key feature of cell selective gene regulation (Molecular Cell 29:611, 2008; Molecular Cell 43:145, 2011). Local transitions in chromatin access (often characterized as DNaseI hypersensitive sites (DHSs)) are o...

Background: Adrenal vein sampling (AVS) remains the gold-standard for distinguishing unilateral and bilateral disease in primary aldosteronism (PA). However, it is invasive, technically demanding, and may yield inconclusive or equivocal results. 11C-Metomidate PET-CT (11C-MTO-PET-CT) is a non-invasive alternative to AVS for localising unilateral aldosterone-producing adenomas (APAs).Methods/patients: We report a retrospective analys...

Objective: Head-to-head data comparing selpercatinib, a highly selective and potent RE arranged during Transfection (RET) kinase inhibitor with CNS activity, to standard treatment of RET-altered medullary thyroid cancer (MTC; cabozantinib or vandetanib) is currently unavailable. This post-hoc comparative effectiveness analysis of data from the phase 1/2 LIBRETTO-001 trial compared investigator-assessed outcomes among patients with RET</e...

Background: General population screening for type 1 diabetes (T1D) using islet autoantibodies (IAb) is gaining international momentum, since screening reduces diabetic ketoacidosis, hospitalisation and identifies individuals eligible for future preventative treatments. Qualitative studies have only been undertaken in at-risk individuals (1). We therefore aimed to explore parents’ experiences of their child taking part in a general population T1D screening...

Introduction: Adrenal venous sampling (AVS) is the criterion standard method of lateralisation in primary aldosteronism (PA). Despite this pivotal role, there is limited consensus and significant variability between centres related to many of the technical aspects of AVS. In this study, we sought to address whether variations in two different technical aspects of AVS altered parameters and interpretation, namely: 1. Peripheral sample site 2. Method of adrenal vein (AV) venesec...

Background: After adrenalectomy (ADX) for primary aldosteronism (PA), approximately 30% of patients achieve clinical success (normalisation of home BP); many additional patients report feeling subjectively better. We used the non-randomised MATCH study1 to further assess quality of life (QoL) changes in participants.Objective: Assess QoL using the 36-item Short Form Health Survey (SF-36) after surgical treatment of unilateral PA and medical treatment of ...

Primary aldosteronism (PA) is the potentially curable cause of high-risk hypertension in 5-10% of unselected patients. Diagnosis and lateralisation of PA is challenging and complex. Outcomes post total adrenalectomy, the standard treatment for unilateral aldosterone producing adenomas (APAs), are variable. Between 30-60% are cured (1), but prediction of outcome is unreliable, and some patients are reluctant to have abdominal surgery to remove a whole adrenal gland. Endoscopic ...

Background: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are commonly characterized by overexpression of somatostatin receptor subtype 2 (SSTR2), which can be targeted by radiopharmaceutical therapy (RPT) via radiolabeled somatostatin analogues (SSAs). RYZ101 (Ac-225 DOTATATE) is a first-in-class, highly potent alpha-emitting RPT being developed for the treatment of SSTR2+ solid tumors. Alpha-particles (such as emitted by Actinium-225) have a sho...

Background: Primary Aldosteronism (PA) is the commonest curable cause of hypertension. Whole exome sequencing (WES) of an aldosterone producing adenoma from a 46-year-old man with resistant hypertension revealed a novel somatic mutation (Val380Asp) of the single transmembrane domain of Cell Adhesion Molecule-1 (CADM1). A Gly379Asp mutation was identified by WES of a PA patient in Munich. Both patients were cured of hypertension by adrenalectomy.Method: A...

Background: PA is the commonest curable cause of hypertension. Whole exome sequencing (WES) in 2011 and 2013 identified common somatic mutations in genes regulating membrane polarisation in 60-80% of aldosterone-producing adenomas (APA). In search of the missing variants, we undertook further WES. One APA from a 46-year-old gentleman revealed a novel somatic mutation (Val380Asp); which introduced a charged amino-acid into the single transmembrane domain of Cell Adhesion Molecu...