Searchable abstracts of presentations at key conferences in endocrinology

ea0077oc3.6 | Metabolism, Obesity and Diabetes | SFEBES2021

Stimulation of motilin secretion by bile, free fatty acids and acidification in human duodenal organoids

Miedzybrodzka Emily L , Foreman Rachel E , Lu Van B , George Amy L , Smith Christopher A , Larraufie Pierre , Kay Richard G , Goldspink Deborah A , Reimann Frank , Gribble Fiona M

Objective: Motilin is a proximal small intestinal hormone with roles in gastrointestinal motility, gallbladder emptying and hunger initiation. The molecular mechanisms underlying motilin release in response to fats, bile and duodenal acidification are poorly understood, in part due a lack of suitable cellular and rodent models. We therefore generated a novel human intestinal organoid model with fluorescently labelled motilin-expressing M-cells, which we used to establish the k...

ea0077oc4.1 | Adrenal and Cardiovascular | SFEBES2021

Development of [18F]AldoView as the first highly selective aldosterone synthase PET tracer for imaging of patients with Primary Hyperaldosteronism.

Sander Kerstin , Gendron Thibault , Cybulska Klaudia A. , Sirindil Faith , Zhou Jonhua , Kalber Tammy L. , Lythgoe Mark F. , Kurzawinski Tom R. , Brown Morris J. , Arstad Erik

Background: Inappropriately high aldosterone in patients with primary hyperaldosteronism (PHA) is due to increased aldosterone synthase (CYP11B2) activity. Selective in vivo imaging of overexpressed CYP11B2 in adrenals with positron emission tomography (PET) has not yet been achieved due to close homology of enzymes involved in aldosterone and cortisol (CYP11B1) synthesis.Aim: Synthesize a fluorine-18 labelled highly selective CYP11B2 inhibitor,...

ea0077oc4.2 | Adrenal and Cardiovascular | SFEBES2021

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Argentesi Giulia , Azizan Elena , Zhou Junhua , Cabrera Claudia , O’Toole Sam , Wu Xilin , Goodchild Emily , Cottrell Emily , Marker Alison , Senanayake Russell , Garg Sumedha , Jordan Suzanne , Berney Dan , Gluck Anna , Lines Kate , Thakker Rajesh V , Tuthill Antoinette , Joyce Caroline , Karet Frankl Fiona , Metherell Lou , Teo Ada , Gurnell Mark , Parvanta Laila , Drake William , Wozniak Eva , Mein Chaz , Kinsler Veronika , Storr Helen , Brown Morris

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...

ea0077oc4.3 | Adrenal and Cardiovascular | SFEBES2021

[11C]Metomidate PET/CT can aid decision-making in patients with primary aldosteronism

Senanayake Russell , Gillett Daniel , Ali Zahabia , Bashari Waiel , MacFarlane James , Koulouri Olympia , van der Meulen Merel , Powlson Andrew , Challis Benjamin , Palma August , Hu Lihua , Aloj Luigi , Mendichovszky Iosif , Cuthbertson Dan , Shore Susannah , Levy Miles , Drake William , Brown Morris , Kosmoliaptsis Vasilis , Marker Alison , Cheow Heok , Gurnell Mark

Background: Primary aldosteronism (PA) is the leading, potentially reversible, cause of secondary hypertension. For most patients in whom surgery is being considered, adrenal vein sampling (AVS) is recommended to distinguish unilateral and bilateral causes. However, AVS remains technically challenging, and a significant proportion of patients are unable to progress to surgery because AVS is unavailable or unsuccessful. We have explored whether [11C]Metomidate PET/CT...

ea0077oc4.4 | Adrenal and Cardiovascular | SFEBES2021

24-hour dynamics of free tissue adrenal hormones: A description of healthy normal variation

Upton Thomas , Zavala Eder , Russell Georgina , Oksnes Marianne , Grytaas Marianne , Simunkova Katerina , Botusan Ileana , Berinder Katarina , Bensing Sophie , Vassiliadi Dimitra , Methlie Paal , Kampe Olle , Tsagarakis Stelios , Husebye Eystein , Lightman Stafford

Adrenal hormones possess both circadian and ultradian rhythms, making interpretation of single time point measurements difficult, particularly in the context of suspected endocrine disease. Attempting to capture either normal or pathological rhythms in detail by traditional measurement of blood is impractical and generally unfeasible. However, minimally invasive microdialysis sampling of free tissue hormones coupled with a portable fraction collector (U-RHYTHM), and a targeted...

ea0077oc4.5 | Adrenal and Cardiovascular | SFEBES2021

Circulating cell-free DNA-based biomarkers as a tool for disease surveillance in adrenocortical carcinoma

Smith Gabrielle , Lippert Juliane , Altieri Barbara , Elhassan Yasir , Landwehr Laura , Prete Alessandro , Appenzeller Silke , Chortis Vasileios , Steinhauer Sonja , Asia Miriam , Sutcliffe Robert , Arlt Wiebke , Fassnacht Martin , Ronchi Cristina

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. Here we investigated the role of circulating cell-free DNA (ccfDNA) in ACC monitoring. We extracted ccfDNA from 1-4 ml EDTA-plasma using the Nonacus Cell3TMXtract or the Qiagen QIAamp MinElute kit and quantified by fluorimeter. We investigated 63 patients with ACC (25M/38F, 52±...

ea0077oc4.6 | Adrenal and Cardiovascular | SFEBES2021

Glucocorticoids and the Vascular Molecular Clock: Implications in Vascular Function Control

Krilis Georgios , Bailey Matthew , Ivy Jessica

Glucocorticoids synchronise peripheral clocks with the master clock in the suprachiasmatic nucleus of the brain. In humans and mice, abnormal glucocorticoid rhythms induce blood pressure abnormalities accompanied by vascular dysfunction. The mechanisms of this remain unclear. We hypothesise that excessive activation of the glucocorticoid receptor (GR) disrupts circadian clock signalling, altering vascular function and inducing non-dipping blood pressure. We characterise the va...

ea0077oc5.1 | Bone and Calcium | SFEBES2021

Successful adeno-associated virus mediated neonatal gene therapy treatment of hypophosphatasia murine model resulted in bone maturation and increased survival to at least 18 months

Matsumoto Tae , Miyake Noriko , Zhao Dongwei , Narisawa Sonoko , Millan Jose , Miyake Koichi

Hypophosphatasia (HPP) is an inherited skeletal disease characterized by defective bone mineralization due to a deficiency in tissue-nonspecific alkaline phosphatase (TNALP). Patients with the severe infantile form of HPP have a poor prognosis that often results in high mortality by one year. Asfotase alfa is an approved therapy for HPP, while requires chronic injections to maintain efficacy. To develop a one-time gene therapy for HPP, we examined the safety and efficacy of AA...

ea0077oc5.2 | Bone and Calcium | SFEBES2021

Gastric inhibitory polypeptide (GIP) reduces human osteoclast activity by suppressing multiple signalling pathways

Hansen Morten S , Soe Kent , Gorvin Caroline M , Frost Morten

Gastric inhibitory polypeptide (GIP) is a post-prandially secreted gut hormone that acts upon the GIP-receptor (GIPR), to stimulate insulin secretion. Animal studies indicate that GIP influences bone remodelling, and in humans, GIP administration decreases levels of bone resorption markers. However, the mechanisms by which GIP influences resorption remain to be elucidated. Therefore, we investigated how GIP (10nM) affects bone cell activity using primary human osteoclasts, hum...

ea0077oc5.3 | Bone and Calcium | SFEBES2021

Role of Intact and C-Terminal FGF-23 Assays in the Investigation of Metabolic Bone Disease.

Jethwa Kishan , Bhatti Sumbal , Chipchase Allison , Piec Isabelle , Fraser William , Turner Jeremy

Fibroblast growth factor 23 (FGF-23) is a phosphatonin produced by osteocytes in response to serum phosphate concentration. Immunoassays are widely employed to detect C-terminal fragments of FGF-23 (cFGF-23). Quantitative assays for intact FGF-23 (iFGF-23) measurement are also available. Causes of increased FGF-23 include Tumour Induced Osteomalacia (TIO), X-linked hypophosphataemic rickets (XLH) and end stage renal disease (ESRD). We observed that some individuals, with no id...