Endocrine Abstracts

Introduction Vascular adhesion protein-1 (VAP-1) is a known driver of hepatic inflammation and fibrosis, with elevated levels detected in the circulation in disease. We studied the tissue expression of VAP-1 in midgut NETs and carcinoid heart disease (CHD) alongside circulating soluble VAP-1 (sVAP-1) to determine the role of VAP-1 in NETs.Methods Expression of VAP-1 and inflammatory and stromal markers in midgut NETs tissue, CHD valves and control valves...

Background: We conducted whole-exome sequencing (WES) of germline(g) and somatic(s) DNA from a prospective cohort of patients with NENs (n =151) to study the genetic predisposition to NENs.Methods: Variants obtained from gWES were filtered using a standard bio-informatics pipeline. Variant Effect Predictor (Release 107) was applied to obtain population allele frequencies. Variants were restricted to those among 974 genes obtained by combining pu...

Background: Peptide receptor radionuclide therapy (PRRT) is a form of targeted systemic radiopharmaceutical therapy that has been approved for treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Persistent hematologic dysfunction is a recognized potential long-term toxicity after PRRT, including the development of hematologic malignancies and persistent cytopenias. Therapy-related myeloid neoplasms (t-MN) are a well-recognized entity that ...

Introduction: MANEC is a rare diagnosis and little is known on its epidemiology/prognosis/management.Methods: Demographic/clinical-pathological/survival data of patients with a diagnosis of MANEC (2010 WHO criteria) from five European centres were retrospectively reviewed.Results: Sixty-six patients were identified (09/80–07/17); median age: 62.5 years (range 34–89); male: 66.7%; ECOG-PS 0-1: 59%; primary tumours from: sm...

Introduction: Non-alcoholic fatty liver disease (NAFLD) is associated with dysregulated glucocorticoid metabolism. Advanced stages of NAFLD are associated with adverse outcome and current strategies to stage disease severity are still reliant upon liver biopsy. We have previously described changes to enzymatic pathways that regulate cortisol bioavailability; 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1) regenerates cortisol from inactive cortisone, and A-ring re...

Background: Hypothalamic KNDy neurons have recently been identified as key regulators of reproductive function by releasing three neuropeptides namely kisspeptin, neurokinin B (NKB) and dynorphin. Animal studies show they interact to control pulsatile GnRH release, which is vital for fertility. In animals, kisspeptin stimulates, NKB modulates and the opioid dynorphin inhibits GnRH pulsatility. However, the interaction of these peptides has never been studied in humans. To inve...

Background: CHI is a cause of severe hypoglycaemia in children. Diazoxide (KATP channel agonist) is used as first-line treatment but is known to cause severe hypertrichosis and reduced appetite in children. Diazoxide unresponsive CHI us treated with daily octreotide subcutaneous injections (3–4 times/day).Objective and hypotheses: To evaluate the efficacy, safety and pharmacokinetics of long acting Somatostatin analogue (Lanreotide) thera...

Kisspeptin is a recently identified reproductive hormone which serves as a crucial activator of the Hypothalamic–Pituitary–Gonadal (HPG) axis via stimulation of GnRH neurones. We have previously observed that a single kisspeptin injection increases LH pulsatility while twice daily kisspeptin injections can even advance the menstrual cycle. Furthermore, we have demonstrated that kisspeptin restores LH pulsatility in women with hypothalamic amenorrhoea and can potently...

Background: PRRT, licensed for gastroenteropancreatic (GEP) NETs, has been used with somatostatin analogues such as lanreotide autogel (LAN). PRELUDE is the first international, multicentre retrospective study, with central radiology reading, to describe use of LAN with PRRT (LAN-PRRT) in advanced NETs.Methods: PRELUDE (NCT02788578) was an international, retrospective, non-comparative analysis of medical records of patients receiving LAN with 177Lu-DOTAT...

Objectives: Diazoxide is first line treatment for hypoglycaemia due to hyperinsulinaemic hypoglycaemia (HH). Although sporadic cases of pulmonary hypertension (PH) have been reported, no HH cohort has been systematically characterised to understand severity and risk factors for diazoxide-induced PH.Methods: To investigate the onset, progress and associated factors in PH, patients with HH who developed diazoxide-induced PH in 4 regional centres were retro...