Searchable abstracts of presentations at key conferences in endocrinology

ea0059p224 | Thyroid | SFEBES2018

Identification of novel sodium iodide symporter (NIS) interactors which modulate radioiodine uptake

Fletcher Alice , Poole Vikki , Thornton Caitlin , Baker Kate , Thompson Rebecca , Nieto Hannah , Alshahrani Mohammed , Read Martin , Turnell Andy , Boelaert Kristien , Smith Vicki , McCabe Chris

Patients termed to have radioiodine-refractory differentiated thyroid cancer (RR-DTC) cannot accumulate sufficient radioiodine for a therapeutic response due to sodium iodide symporter (NIS) dysregulation via diminished expression and/or altered plasma membrane (PM) localisation. Currently, the regulation of NIS localisation remains poorly defined and despite protein-protein interactions being well-described to modulate trafficking events, the NIS interactome is limited. Previ...

ea0037ep927 | Thyroid (non-cancer) | ECE2015

Health-related quality of life is reduced in treated primary hypothyroidism and with lower fT3/fT4-ratio

van Loon Hannah C M , Wouters Hanneke J C M , Kobold Anneke Muller , Slagter Sandra N , Links Thera P , van der Klauw Melanie M , Wolffenbuttel Bruce H R

Introduction: Despite adequate treatment with LT4 monotherapy, many patients with primary hypothyroidism still report complaints, as this treatment can not exactly imitate the endogenous homeostasis. We examined whether the different domains of HR-QOL were affected by the existence of a thyroid disorder and use of LT4 substitution, and whether a lower ratio of free triiodothyronine (fT3)–free thyroxine (fT4)</sup...

ea0070oc5.4 | Thyroid | ECE2020

Drug repurposing identifies inhibitors of the proteostasis network to augment radioiodine uptake in combinatorial approaches targeting thyroid cancer

Read Martin , Brookes Katie , Fletcher Alice , Thornton Caitlin , Alshahrani Mohammed , Khan Rashida , Nieto Hannah , Adcock Holly , Webster Jamie , Cox Liam , Alderwick Luke , Boelaert Kristien , Smith Vicki , McCabe Christopher

New combinatorial drug strategies are urgently needed to improve radioiodine (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. Drug repurposing offers the promise of identifying already approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. However, a lack of thyroid cell-based assays amenable to high-throughput screening has limited progress. We utilised the mutated yellow...

ea0021p204 | Endocrine tumours and neoplasia | SFEBES2009

Temozolomide-induced regression of hepatic metastases in a pituitary corticotroph carcinoma with low O6-methylguanine-DNA methyltransferase expression

Burton Hannah , Annamalai Anand K , Dean Andrew , Kovacs Kalman , Antoun Nagui , Kirollos Ramez W , Simpson Helen L , Jeffries Sarah J , Burnet Neil G , Gurnell Mark

Background: Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours, and carries a poor prognosis (mean survival <4 years), with standard chemotherapeutic regimens showing limited efficacy. However, recent evidence suggests that temozolomide, an orally active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. Low levels of expression of the DNA-repair enzyme ...

ea0056oc10.3 | Cardiovascular aspects of endocrine diseases | ECE2018

ARMC5 variants and risk of hypertension in African Americans: Minority Health-GRID study

Zilbermint Mihail , Gaye Amadou , Berthon Annabel , Hannah-Shmouni Fady , Faucz Fabio , Minority Health-GRID Network Fabio , Davis Adam , Gibbons Gary , Lodish Maya , Stratakis Constantine

Context: Hypertension is one of the most preventable risk factors for cardiovascular disease and death. Up to 42.1% of non-Hispanic African-American subjects have hypertension. We recently found that germline ARMC5 variants may play a role in primary aldosteronism, particularly in African-Americans.Objective: We investigated a cohort of participants in the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) stud...

ea0045p53 | Miscellaneous/other | BSPED2016

Vineland adaptive behaviour scales to identify neurodevelopmental problems in children with Congenital Hyperinsulinism (CHI)

Mohamed Zainaba , Banerjee Indraneel , Michaelidou Maria , Estabanez Maria , Dunne Mark J , Collins Hannah , Rigby Lindsey , Bowden Louise , Rust Stewart , Nicholson Jacqueline

Background: Congenital Hyperinsulinism (CHI) is a disease of severe hypoglycaemia due to insulin hypersecretion, that can be recognised either early or late in childhood. CHI is associated with adverse neurodevelopmental outcomes. The Vineland Adaptive Behaviour Scales Second Edition (VABS-II) is a parent-report measure of intellectual and developmental functioning, which could be used to screen children with CHI for impairments.Aims: To investigate reli...

ea0094oc2.1 | Endocrine Cancer and Late Effects | SFEBES2023

Manipulating NIS endocytosis as a druggable target to enhance radioiodide uptake and prognostic indictor of thyroid cancer recurrence

Read Martin , Brookes Katie , Zha Ling , Manivannan Selvambigai , Kim Jana , Firth George , Sunassee Kavitha , Blower Philip , Boelaert Kristien , Nieto Hannah , Smith Vicki , McCabe Christopher

Background: Diminished sodium iodide symporter (NIS) activity at the plasma membrane (PM) is frequently associated with suboptimal radioiodide (RAI) uptake and poor prognosis in differentiated thyroid cancer (DTC). Endocytosis is a key determinant of symporter activity, with our recent study demonstrating specific interaction of NIS with Adaptor Protein 2 (AP2) – a central player in endocytosis. Here, our objective was to determine whether NIS endocytosis...

ea0094oc7.1 | Thyroid | SFEBES2023

A copper-based metabolite of disulfiram upregulates sodium iodide symporter (NIS) gene expression to enhance thyroidal uptake of radionuclides in vivo

Brookes Katie , Zha Ling , Small Benjamin , Kim Jana , Manivannan Selvambigai , Thornton Caitlin , Kannappan Vinodh , Wang Weiguang , Nieto Hannah , Sunassee Kavitha , Blower Philip , Smith Vicki , Read Martin , McCabe Christopher

Introduction: New approaches to improve radioiodide (RAI) uptake are urgently required in RAI-refractory thyroid cancer. We previously identified disulfiram as a leading candidate to induce sodium iodide symporter (NIS) activity and promote RAI uptake. In vivo, DSF is metabolised to diethyldithiocarbamate (DDC) which binds metal ions. Here, we aimed to gain a mechanistic understanding of how DSF and it’s related metabolite Cu(DDC)2 imp...

ea0099p27 | Adrenal and Cardiovascular Endocrinology | ECE2024

Impact on immunophenotype of switching from conventional glucocorticoids to modified-release hydrocortisone in congenital adrenal hyperplasia

Ziegler Selina , Nowotny Hanna , Choi Hannah , Tschaidse Lea , Auer Matthias , Welp Ann-Christin , Gottschlich Adrian , Kobold Sebastian , Rothenfusser Simon , Reisch Nicole

Background: Previous research has revealed variances in the composition of immune cells among patients with congenital adrenal hyperplasia (CAH) on conventional glucocorticoid (GC) replacement therapy compared to healthy controls. Modified-release hydrocortisone (MR-HC) optimizes cortisol pharmacokinetics, aligning with a more physiological circadian cortisol rhythm. This study therefore aims to assess the impact on the immune cell profile when transitioning patients with CAH ...

ea0034p13 | Bone | SFEBES2014

Mutational analysis of the adaptor protein 2 sigma subunit (AP2S1) gene: search for autosomal dominant hypocalcaemia type 3 (ADH3)

Rogers Angela , Nesbit M Andrew , Hannan Fadil M , Howles Sarah A , Cranston Treena , Allgrove Jeremy , Bevan John S , Bano Gul , Brain Caroline , Datta Vipan , Hodgson Shirley V , Izatt Louise , Millar-Jones Lynne , Pearce Simon H , Robertson Lisa , Selby Peter L , Shine Brian , Snape Katie , Warner Justin , Thakker Rajesh V

Familial hypocalciuric hypercalcaemia types 1, 2, and 3 (FHH1, FHH2, and FHH3) are caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), G-protein subunit α11 (Gα11) and adaptor protein 2 sigma subunit (AP2σ), respectively; whilst autosomal dominant hypocalcaemia types 1 and 2 (ADH1 and ADH2) are due to gain-of-function mutations of CaSR and Gα11, respectively. We therefore hypothesised that gain-of-function AP2σ mutations may re...