Searchable abstracts of presentations at key conferences in endocrinology

ea0044p136 | Neoplasia, cancer and late effects | SFEBES2016

The role of primary cilia in the molecular pathogenesis of phaeochromocytoma

O'Toole Sam , Srirangalingam Umasuthan , Drake William , Chapple Paul

Phaeochromocytomas are life-threatening catecholamine-producing tumours of the adrenal medulla. Our understanding of their pathogenesis is incomplete, with limited ability to predict malignant potential and disappointing treatment results in disseminated disease. Phaeochromocytomas occur in the inherited cancer syndrome von Hippel-Lindau (VHL). One function of VHL protein is in the formation and maintenance of primary cilia. These are microtubule-based organelles that protrude...

ea0038p155 | Neoplasia, cancer and late effects | SFEBES2015

Primary cilia: a new player in phaeochromocytoma pathogenesis?

O'Toole Sam , Srirangalingam Umasuthan , Drake William , Chapple Paul

Introduction: Primary, non-motile, cilia are microtubule-based organelles that protrude from the cell membrane into the extracellular environment of virtually all nucleated mammalian cells. They function as signalling platforms involved in the transduction of extracellular stimuli and have an important role in cell cycle regulation. Disruption of primary cilia structure and therefore function has been identified in a range of cancers including kidney, breast, pancreatic and pr...

ea0077oc2.6 | Endocrine Cancer and Late Effects | SFEBES2021

Transcriptomic analysis of succinate dehydrogenase subunit deleted cells to identify molecular mechanisms underlying the increased metastatic potential of SDHB-deficient tumours

Salsbury Grace , Hall Charlotte , Lim Eugenie , Read Jordan , Akker Scott , Chapple Paul

Mutations in each of the 4 subunits of succinate dehydrogenase (SDH) – SDHA, B, C and D predispose to development of phaeochromocytomas and paragangliomas. Loss of SDH function leads to accumulation of succinate which acts as an oncometabolite to drive tumourigenesis. However, mutations in SDHB have an increased likelihood of causing metastatic disease, compared to mutations in the other SDH subunits. The reasons behind this increased risk remai...

ea0077lb15 | Late Breaking | SFEBES2021

Development and testing of a novel ‘GrowthMonitor’ Smartphone App for growth monitoring and the detection of growth disorders

Thaventhiran Thilipan , Harding Vincent , Hsu Anne , Dunkel Leo , Chapple Paul , Storr Helen

Background: Childhood growth is an indicator of health/well-being. Growth monitoring identifies treatable conditions in apparently healthy children and prevents inappropriate referrals. Systematic growth monitoring is not currently a UK priority and growth disorders are frequently diagnosed late.Objective: Develop and test the accuracy of GrowthMonitor, an app which enables families to measure a child’s height at home as a cost-effective alternative...

ea0015oc25 | Pituitary, disease | SFEBES2008

Identification of MC2R receptor accessory protein domains required for interaction with MC2R and formation of a functional ACTH responsive receptor

Webb Tom , Chapple Paul , Metherell Lou , Cooray Sadani , Cheetham Mike , Clark Adrian

MC2R is the smallest member of the GPCR superfamily and belongs to the melanocortin subfamily of receptors. The pituitary hormone ACTH acts through MC2R to induce the intracellular production cAMP and the stimulation of steroidogenesis. We have previously shown that MC2R interacts with a single-transmembrane domain protein called MRAP (melanocortin-2 receptor accessory protein) and is required for the functional expression of MC2R. Both MC2R and MRAP are mutated in the rare re...

ea0077lb39 | Late Breaking | SFEBES2021

Metabolomic analysis of succinate dehydrogenase subunit knockout in phaeochromocytoma and neuroblastoma cell lines

Salsbury Grace , Read Jordan E , Morales Valle , Hall Charlotte L , Lim Eugenie S , Akker Scott A , Bianchi Katiuscia , Chapple Paul

Loss of function of succinate dehydrogenase (SDH), caused by mutations in each of the 4 subunits – SDHA/B/C and D – is associated with development of phaeochromocytomas and paragangliomas (PPGLs). The mutations lead to loss of enzymatic activity and subsequent accumulation of the oncometabolite succinate, a driver of tumourigenesis. It is well established but poorly understood why mutations in SDHB are associated with more aggressi...

ea0028p241 | Pituitary | SFEBES2012

Can the stability of variant aryl hydrocarbon receptor interacting protein (AIP) be a marker for pathogenicity in FIPA (familial isolated pituitary adenoma)?

Martucci Federico , Trivellin Giampaolo , Garcia Edwin , Dalantaeva Nadezhda , Chapple Paul , Pecori Giraldi Francesca , Grossman Ashley , Korbonits Marta

Background: 20% of the familial isolated pituitary adenoma (FIPA) population harbour an aryl hydrocarbon receptor-interacting protein (AIP) gene mutation. The recognition of whether a variant is pathogenic can be difficult, in cases where the observed change does not lead to a truncated protein. Segregation with disease in a family, in silico predictions, loss of heterozigosity in the tumour, in vitro functional studies and screening of the variant in controls may help in asce...

ea0015p326 | Steroids | SFEBES2008

The cell surface expression of MC2R mutations found in familial glucocorticoid deficiency

Chung Teng-Teng LL , Cooray Sadani , Webb Tom , Metherell Lou , King Peter , Chapple Paul , Clark Adrian JL

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease due in ∼25% of cases to defects in the ACTH receptor (melcanocortin 2 receptor -MC2R). Slow progress in characterization of these mutations has been made in view of the difficulty in establishing a functional heterologous cell transfection system for the MC2R, and the best available models relate to the mouse Y6/OS3 cell lines. However we have shown previously that the melanocortin 2 receptor ...

ea0085oc10.3 | Oral Communications 10 | BSPED2022

Development and testing of a novel ‘Growth monitor’ Smartphone App for growth monitoring and the detection of growth disorders

Thaventhiran Thilipan , Orr Joanna , Morris Joan , Hsu Ann , Martin Lee , Davies Kate , Harding Vincent , Dunkel Leo , Chapple Paul , Storr Helen

Background: Growth monitoring identifies treatable conditions in apparently healthy children and prevents inappropriate referrals. Systematic growth monitoring is not currently a UK priority and growth disorders are frequently diagnosed late.Objectives: Develop and test the accuracy of a smartphone app which enables families to measure a child’s height at home as a cost-effective alternative to primary care growth monitoring.M...

ea0015p192 | Endocrine tumours and neoplasia | SFEBES2008

AIP: a protein mutated in familial acromegaly plays a role in the regulation of cell proliferation and shows cell-type specific subcellular localisation

Leontiou Chrysanthia A , Gueorguiev Maria , Hassan Sevda , van der Spuy Jacqueline , Lolli Francesca , Stolbrink Maria , Christian Helen , Wray Jennifer , Bishop-Bailey David , Berney Dan M , Frohman Lawrence A , Chapple Paul J , Grossman Ashley B , Korbonits Marta

Mutations in AIP have been identified in a significant proportion of families with pituitary adenomas, most commonly in familial acromegaly. However, no data are available about the pituitary expression of AIP and how lack of AIP is involved in tumorigenesis.We identified 10 kindreds with AIP mutations out of 31 families. We studied RNA and protein expression of AIP in normal as well as familial and sporadic pituitary adenomas. In the normal pituitary st...