Searchable abstracts of presentations at key conferences in endocrinology

ea0059cc2 | Featured Clinical Cases | SFEBES2018

Missplicing due to a silent exonic substitution in the T-box transcription factor TBX19 resulting in Isolated ACTH deficiency

Maudhoo Ashwini , Maharaj Avinaash , Buonocore Federica , Martos-Moreno Gabriel Angel , Argente Jesus , Achermann John , Chan Li , Metherell Lou

Background: Congenital isolated ACTH deficiency (IAD) is a rare condition characterised by low plasma ACTH and serum cortisol with normal production of other pituitary hormones. TBX19 is a T-box pituitary restricted transcription factor important for POMC gene transcription and terminal differentiation of POMC-expressing cells. TBX19 gene mutations have been shown to cause neonatal-onset congenital IAD. To date 25 mutations in TBX19 have been described, five ...

ea0037ep396 | Diabetes (pathiophysiology & epitemiology) | ECE2015

Glycaemic control is comparable in patients with or without significant hepatic fibrosis as assessed by NAFLD fibrosis score

Chin Jun Liong , Chan Grace , Sea-Pui Sin Phyllis , Siddiqui Zeshan , O'Rathallaigh Eoin , Aftab Abdur Rahman , Courtney Garry , McGurk Colm

Background and aims: Non-alcohol fatty liver disease (NAFLD) is increasingly recognised in diabetic patients with metabolic syndrome. Patients with poorly-controlled diabetes and metabolic syndrome are likely to have significant liver inflammation leading to fibrosis. NAFLD fibrosis score (NFS) is a validated non-invasive scoring system that identifies liver fibrosis in patients with NAFLD. The aim of this study is to examine the glycaemic control in patients with or without s...

ea0036P4 | (1) | BSPED2014

cDNA analysis reveals NNT pseudoexon activation in two siblings with familial glucocorticoid deficiency

Chan Li , Novoselova Tatiana , Rath Shoshana , Carpenter Karen , Pachter Nick , Price Glynis , Dickinson Jan , Choong Cathy , Metherell Lou

Aberrant pseudoexon inclusion is rarely recognised as a cause of human disease. Here we report two novel, compound heterozygous mutations in nicotinamide nucleotide transhydrogenase (NNT), one of which activates a pseudoexon, as the cause of familial glucocorticoid deficiency in two siblings. Whole-exome sequencing identified a single novel, heterozygous variant (R71X) in both affected individuals. Follow-up cDNA analysis identified the pseudoexon inclusion (p.P998_D9...

ea0036P52 | (1) | BSPED2014

Improving health-related outcomes for childhood craniopharyngiomas with a modern individualised conservative surgical strategy and adjuvant focussed radiation; experience at a single centre (great ormond street hospital – GOSH) 2009–2013

Losa Laura , Gan Hoong-Wei , Ederies Ash , Kuczynski Adam , Bowman Richard , Chan Yen-Ching , Aquilina Kristian , Spoudeas Helen A

Introduction: Craniopharyngiomas are rare, pituitary tumours which, though benign with good survival, carry high neuroendocrine morbidity. Optimum management remains controversial despite a UK consensus strategy (2005).Aim: To study disease- and treatment-related neuroendocrine, visual and cognitive outcomes in our most recent cohort, managed with individualised multidisciplinary decision making to limit hypothalamic morbidity.Pati...

ea0036P60 | (1) | BSPED2014

Melanocortin 2 receptor accessory protein 2 (Mrap2) regulates hypothalamic melanocortin-4-receptor trafficking in vivo

Novoselova Tatiana , Larder Rachel , Rimmington Debra , Lelliott Chris , Wynn Elizabeth , O'Rahilly Stephen , Clark Adrian , Logan Darren , Coll Anthony , Chan Li

Recently, rare loss-of-function mutations of melanocortin-2-receptor accessory protein 2 (MRAP2) have been associated with severe, early-onset obesity in humans. In addition, whole body deletion and targeted brain specific deletion of the Mrap2 gene resulted in severe obesity in mice. In vitro data have shown Mrap2 interaction with the melanocortin-4-receptor (MC4R) affecting receptor signalling as a consequence. However, the mechanism by which Mrap2...

ea0058oc4.4 | Oral Communications 4 | BSPED2018

Identification and characterisation of a small-molecule ACTH receptor/Melanocortin-2-receptor antagonist

Chan Li , Hussain Mashal , Forfar Rachel , Khurana Puneet , Cook Jennifer , Lewis Steve , McIver Ed , Jerman Jeff , Taylor Debra , Clark Adrian

The overproduction of ACTH, in conditions such as Congenital Adrenal Hyperplasia (CAH) leads to significant morbidity. Current treatment with glucocorticoids does not adequately suppress plasma ACTH, resulting in excess adrenal androgen production. At present, there is no effective medical treatment that would directly block ACTH action. Such a therapy, especially one that can be orally administered, would be of great clinical value allowing a ‘block and replace’ tre...

ea0029p594 | Diabetes | ICEECE2012

Proteomic identification of plasma biomarkers in type 1 diabetes mellitus: an implication of hemopexin overexpression in diabetes mellitus

Lee Y. , Chen C. , Chen Y. , Lu Y. , Lee W. , Lu C. , Chen Y. , Chou H. , Timms J. , Chan H.

Type 1 diabetes mellitus (T1DM) not only is congenital disease that known as insulin-dependent diabetes, often occurs in children and adolescents. Recent advances in quantitative proteomics including fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) and matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) have offered opportunities to discover plasma proteins as biomarkers for tracking the progression and for underst...

ea0029p1409 | Pituitary Clinical | ICEECE2012

Increased risk of hypothalamic pituitary dysfunction amongst nasopharyngeal cancer survivors with the use of concurrent chemo-irradiation

Ratnasingam J , Karim N , Paramasivam S , Tan Tong Boon A , Vethakkan S , Choong K , Pendek R , Chan S

Background: Radiotherapy is the mainstay of NPC (nasopharyngeal carcinoma) treatment and recently there is increased use of concurrent chemo-irradiation (CCRT) to improve survival. The irradiation field for NPC includes the base of skull, risking radiation damage to the hypothalamic–pituitary (HP) axis.Aims: To evaluate the prevalence of HP dysfunction in NPC survivors post-irradiation and to compare the risk of developing HP dysfunction amongst pat...

ea0028oc1.7 | Young Endocrinologists prize session | SFEBES2012

Progressive adrenal insufficiency and 46,XY DSD caused by two novel mutations in the cytochrome P450 side-chain cleavage (CYP11A1) gene

Parajes Silvia , Chan Angel , But Betty , Rose Ian , Taylor Angela , Griffin Aliesha , Dhir Vivek , Arlt Wiebke , Krone Nils

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individuals, with nor...

ea0019p201 | Growth and development | SFEBES2009

Monocarboxylate transporter 8 (MCT8) in human fetal central nervous system (CNS) development

Chan S-Y , Martin-Santos A , Loubiere LS , Gonzalez AM , Cox P , Logan A , McCabe CJ , Franklyn JA , Kilby MD

Mutations in the plasma membrane thyroid hormone (TH) transporter, MCT8, are associated with severe global neurological deficits accompanied by abnormal circulating TH levels. We have previously shown that MCT8 over-expression in human neuronal precursor cells (NT2) increases cellular T3 uptake and reduces proliferation.Objectives: To quantify and localise the expression of MCT8 in human fetal CNS and to investigate the role of MCT8 in NT2 neurodifferent...