Searchable abstracts of presentations at key conferences in endocrinology

ea0095p149 | Pituitary and Growth 2 | BSPED2023

Standard clinical diagnostic criteria for Silver–Russell Syndrome frequently overlooks monogenic causes

Palau Helena , Kurup Uttara , Ishida Miho , Maharaj Avinaash V , Davies Justin H. , Storr Helen L.

Background: A diagnosis Silver–Russell Syndrome (SRS) is important for early institution of appropriate management, access to therapy and reduces the burden of diagnostic uncertainty. SRS is molecularly heterogeneous and 11p15 LOM/upd(7)mat account for ~60% cases. Monogenic causes include variants in HMGA2, CDKN1C, IGF-2, PLAG1 and contribute to 5% cases. Clinical SRS diagnosis requires the fulfilment of ≥4/6 Netchine–Harbison Clinical Scoring ...

ea0078OC6.1 | Oral Communications 6 | BSPED2021

Novel dominant negative GH receptor variants provide important insights into GH receptor physiology

Andrews Afiya , Cottrell Emily , Maharaj Avinaash , Ladha Tasneem , Williams Jack , Metherell Louise A , McCormick Peter J , Storr Helen L

Background: Growth hormone insensitivity (GHI) is a continuum defined by normal/elevated growth hormone (GH), low IGF-I levels and growth restriction. Non-classical/mild-moderate GHI is poorly characterised and is frequently underdiagnosed. Heterozygous dominant negative (DN) gene variants located in the regions encoding the intracellular/transmembrane domains of the GH receptor cause a ‘non-classical’ GHI phenotype.Hypothesis/Objective: Detail...

ea0082oc1 | Oral Communications | SFEEU2022

Genetic analysis of patients with undiagnosed short stature identified novel dominant negative GH receptor variants which provide important insights into GHR physiology

Andrews Afiya , Cottrell Emily , Maharaj Avinaash , Ladha Tasneem , Williams Jack , A Metherell Louise , J McCormick Peter , Storr Helen L

Case history: Two unrelated male patients were referred for evaluation of short stature. The first patient aged 16.5 years, had a birth weight of 2.6 kg at term (BWSDS -2.4), height 153 cm (HSDS -3.2) at referral and normal BMI SDS of 0.6. He had early postnatal hypoglycemia, which was conservatively managed, but no other significant clinical history. He had relative macrocephaly and disproportionate short stature. His mother was also short with a similar phenotype (height 147...

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...

ea0085p46 | Pituitary and Growth 1 | BSPED2022

A rare heterozygous IGFI variant impairing IGF-I cleavage and causing postnatal growth failure: a novel disease mechanism offering insights into IGF-I physiology

Cottrell Emily , Andrews Afiya , Williams Jack , Chatterjee Sumana , Edate Sujata , Metherell Louise A. , Hwa Vivian , Storr Helen L.

Background: Pathogenic IGFI gene mutations causing childhood growth failure are extremely rare. Only five autosomal recessive mutations, one IGFI copy number variant and two heterozygous frameshift mutations are reported. Heterozygous missense IGFI mutations haven’t previously been described.Objectives: To identify and functionally characterise a novel missense IGFI variant in a patient with postnatal growth failu...

ea0065cc1 | FEATURED CLINICAL CASE POSTERS | SFEBES2019

Double somatic mutations of CTNNB1 and GNA11 in aldosterone producing adenomas (APAs) presenting in puberty, pregnancy or menopause

Zhou Junhua , Storr Helen , Cottrell Emily , Cabrera Claudia , Argentesi Giulia , Wu Xilin , Goodchild Emily , Azizan Elena , Brown Morris J

Objective: We reported 3 patients with primary aldosteronism who presented at times of high plasma LH, and had somatic CTNNB1 mutations causing ˜100-fold elevation of LHCGR in their APAs (Teo et al. NEJM 2015). Subsequently we identified 4 further patients, but the association with pregnancy was not found by others. Whole exome sequencing (WES) of an APA diagnosed at onset of puberty suggests an explanation.Method: WES of tumour and blood w...

ea0063p734 | Pituitary and Neuroendocrinology 2 | ECE2019

A phase 2 study assessing osilodrostat in children and adolescent patients with Cushing’s disease – Rationale and methods

Storr Helen L , Shah Nalini , Wojna Judi , Han Kevin , Roughton Michael , Pierre Combes Francois , Pultar Philippe , Savage Martin O

Background: In children, Cushing’s disease (CD) presents with a combination of weight gain and slowed linear growth. First-line pituitary surgery is the treatment of choice for most patients. In paediatric patients, the transsphenoidal surgical success rate is 60%–98% when performed by an expert pituitary surgeon. There is a need for additional pharmacological interventions to control hypercortisolaemia, which are currently limited, in children and adolescents. In ph...

ea0049gp195 | Pituitary & endocrine Tumours | ECE2017

Long-term follow-up of a family with a large AIP gene deletion: variable phenotypes and challenges in the management

Marques Pedro , Dang Mary , Ogilvie Arla , Storr Helen , Powell Michael , Grieve Joan , Evason Jane , Kumar Ajith , Korbonits Marta

Introduction: Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 15–30% of familial isolated pituitary adenomas (FIPA). We report a 4-generation FIPA kindred with a heterozygous AIP gene deletion in exon 2, highlighting the benefits of genetic screening and management challenges in affected subjects and asymptomatic carriers.Patients: A 45y woman died of a spinal ependymoma (obligate carrier)...

ea0039ep8 | Adrenal | BSPED2015

Intravenous Etomidate in the management of hypercortisolaemia due to ectopic ACTH producing thymic neuroendocrine tumor

Arya Ved Bhushan , Irvine Vanessa , Rowlands Helen , Sykes Kim , Nicolin Gary , Drake William , Storr Helen , Davies Justin H

Background: Ectopic-ACTH syndrome (EAS) is an extremely rare cause of Cushing’s syndrome in young children. The intensity of ACTH secretion and hypercortisolaemia is greater in EAS than in Cushing’s disease. Control of hypercortisolaemia represents a key management step while awaiting localization of the ACTH source or in preparation to surgery. Etomidate inhibits cortisol synthesis and its rapid onset of action makes it an ideal medication in severe hypercortisolaem...

ea0059cc5 | Featured Clinical Cases | SFEBES2018

A second GH Receptor pseudoexon mutation causing frameshift and severe postnatal growth failure

Cottrell Emily , Maharaj Avinaash , Chatterjee Sumana , Grandone Anna , Cirillo Grazia , del Giudice Emanuele Miraglia , Storr Helen L , Metherell Louise A

Background: GH Insensitivity (GHI) is usually caused by mutations in the GH receptor (GHR). Our centre previously described the first GHR pseudoexon mutation (42700896A>G, c. 618+792A>G). Inclusion of this 108bp pseudoexon is predicted to lead to in-frame insertion of 36 amino acid residues in the dimerization domain of the GHR. This results in defective trafficking rather than impaired signalling, causing partial loss-of-function and moderat...