Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2015

Edinburgh, UK
02 Nov 2015 - 04 Nov 2015

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2-4 November 2015, Edinburgh, UK Further information

Poster Presentations

Neoplasia, cancer and late effects

ea0038p145 | Neoplasia, cancer and late effects | SFEBES2015

Nicotinamide nucleotide transhydrogenase (NNT) as a novel molecular target in adrenocortical carcinoma – impact of NNT knockdown on adrenocortical cell proliferation, redox balance and steroidogenesis

Chortis Vasileios , Taylor Angela , Doig Craig , Meimaridou Eirini , Metherell Lou , Arlt Wiebke , Foster Paul

Nicotinamide nucleotide transhydrogenase (NNT) is a NADPH-generating mitochondrial proton pump with a central role in mitochondrial antioxidant pathways. Recent studies revealed inactivating NNT mutations in patients with familial glucocorticoid deficiency, indicating a selective susceptibility of the adrenal cortex to NNT deficiency and oxidative stress. Here we explored the potential value of NNT as a therapeutic target in adrenocortical cancer. We delineated the distinct ef...

ea0038p146 | Neoplasia, cancer and late effects | SFEBES2015

The somatostatin analogue pasireotide decreased proliferation and increased apoptosis in pancreatic and pituitary neuroendocrine tumors in a MEN1 mouse model

Stevenson Mark , Walls Gerard , Soukup Ben , Lines Kate , Grossman Ashley , Schmid Herbert , Thakker Rajesh

Improved therapies for pancreatic and pituitary neuroendocrine tumors (NETs), which may occur in Multiple Endocrine Neoplasia type 1 (MEN1), are needed. We assessed the effects of pasireotide, a somatostatin analogue with high affinity for somatostatin receptors (SSTRs) −1, −2, −3 and −5, in a mouse model of MEN1. Men1+/− mice treated from 12 months of age with 40 μg/g pasireotide (n=71), or phosphate-buffered sal...

ea0038p147 | Neoplasia, cancer and late effects | SFEBES2015

Steroid sulphatase and G-protein coupled oestrogen receptor in human colorectal cancer: correlation with late-stage disease and potential therapeutic targets

Rahman Habibur , Gilligan Lorna , Hewitt Anne-Marie , Morton Dion , Foster Paul

Steroid sulphatase (STS) liberates sulphated oestrogens into their active forms. In the colon, evidence suggests that although initially pro-apoptotic in healthy mucosa, once malignancy occurs, oestrogens may stimulate colorectal cancer (CRC) proliferation. Moreover, greater intratumoural oestrogen synthesis is negatively associated with survival outcomes in CRC patients. However, little is known about oestrogen metabolism pathways in CRC, and whether alterations in local oest...

ea0038p148 | Neoplasia, cancer and late effects | SFEBES2015

PTTG is phosphorylated at residue T60 and regulates p53 stability, in conjunction with PBF, in head and neck cancer

Modasia Bhavika , Read Martin L , Smith Vicki E , Turnell Andy S , Rae Peter C , Watkins Rachel J , Imruetaicharoenchoke Waraporn , Poole Vikki L , Mehanna Hisham , McCabe Chris J

PTTG is a multifunctional proto-oncogene, overexpressed in thyroid, pituitary and other endocrine cancers. PTTG is also implicated in the pathogenesis of head and neck cancer, where high PTTG expression independently correlates with advanced tumour stage and reduced disease-free survival. Recently, abrogation of residue threonine-60 (T60) has been associated with altered PTTG half-life, chromosomal instability and cell invasion. We therefore generated a phospho-specific antibo...

ea0038p149 | Neoplasia, cancer and late effects | SFEBES2015

Distinct p53 response profiles in transgenic mouse models of thyroid-specific PBF and PTTG expression

Read Martin , Fong Jim , Imruetaicharoenchoke Waraporn , Modasia Bhavika , Lewy Greg , Ryan Gavin , Sharma Neil , Smith Vicki , Watkinson John , Boelaert Kristien , Turnell Andrew , McCabe Christopher

Functional disruption of the tumour suppressor p53 has a critical role in promoting the development of most cancers. The proto-oncogenes PBF and PTTG1 both regulate p53 activity, but the relative contribution of each gene in influencing p53 function has not been delineated, especially in thyroid cancer where both proto-oncogenes are commonly overexpressed. To better understand the interplay between PTTG1, PBF and p53 in vivo, we examined p53 responses in primary thyrocytes cul...

ea0038p150 | Neoplasia, cancer and late effects | SFEBES2015

Follow up of differentiated thyroid cancer survivors during pregnancy: a retrospective analysis

King Rhodri , Rathod Medha , Ward Emma

Differentiated thyroid cancer (DTC) is common in female patients of reproductive age and generally has a good prognosis and so many patients may become pregnant following treatment. Progression of DTC during pregnancy has been reported and may relate to thyroid stimulation by human chorionic gonadotropin (hCG). Until recently suppression of thyrotropin (TSH) by supraphysiological doses of levothyroxine was indicated for all patients following thyroidectomy and radioiodine abla...

ea0038p151 | Neoplasia, cancer and late effects | SFEBES2015

Pituitary-related outcomes of cranial radiotherapy (cXRT) in adults with gliomas

Kyriakakis Nikolaos , Lynch Julie , Orme Steve M , Gerrard Georgina , Hatfield Paul , Loughrey Carmel , Short Susan C , Murray Robert D

Introduction: Radiation-induced hypopituitarism has been well-described in childhood-onset brain tumour survivors, however in adults has received less attention. The aim of this study was to assess the pituitary-related outcomes following cXRT in adults with extra-sellar gliomas.Methods: We retrospectively collected longitudinal data regarding pituitary-related outcomes from medical records of 59 patients, diagnosed with extra-sellar gliomas in adulthood...

ea0038p152 | Neoplasia, cancer and late effects | SFEBES2015

Phenotypic heterogeneity associated with proglucagon-expressing tumours is due to differential processing and secretion of proglucagon-derived peptides

Challis Ben , Albrechtsen Nicolai , Bansiya Vishakha , Burling Keith , Barker Peter , Hartmann Bolette , Gribble Fiona , O'Rahilly Stephen , Holst Jens , Simpson Helen

Context: Pancreatic neuroendocrine tumours (NETs) overexpressing glucagon are associated with phenotypic heterogeneity. Objective: To correlate clinical phenotype with detailed analysis of plasma levels of proglucagon-derived peptides (PGDPs) in subjects with proglucagon-expressing tumours using specific immunoassays and gel filtration profiles to elaborate molecular heterogeneity of PGDPs, before and after somatostatin analogues.Case 1: A 57 year old wo...

ea0038p153 | Neoplasia, cancer and late effects | SFEBES2015

Novel targeted treatment combinations for malignant neuroendocrine tumour olfactory neuroblastoma

Young Karen , Alusi Ghassan , Korbonits Marta

Background: Olfactory neuroblastoma (ONB), a neuroendocrine nasal tumour, exhibits a range of phenotypes from indolent to very aggressive. Even early disease is associated with high (60%) recurrence rates, while advanced disease has 1.5y disease-free and 2.5y overall mean survival. Medical treatments against primary and recurrent disease as well as prognostic biomarkers are urgently required. The few studies available suggest that mTOR/MAPK and Sonic Hedgehog signalling has a ...

ea0038p154 | Neoplasia, cancer and late effects | SFEBES2015

Adrenal pigmentation in PPNAD is a result of melanin deposition and associated with upregulation of the melanocortin 1 receptor

Cavlan Dominic , Storr Helen , Berney Dan , Evagora Chris , King Peter

Primary pigmented nodular adrenal disease (PPNAD) is a form of bilateral adrenocortical hyperplasia characterised by small to normal sized adrenal glands containing multiple small cortical pigmented nodules1. It may occur independently, but 90% of cases are a manifestation of the Carney complex. Most cases of PPNAD are diagnosed before age 30, and are the result of a germline mutation in PRKAR1A or PDE11A, leading to upregulation of cAMP signalling. It is a cause of...

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...

ea0038p156 | Neoplasia, cancer and late effects | SFEBES2015

Adverse metabolic profile in long-term survivors of adult and childhood-onset brain tumours: the role of growth hormone deficiency

Lynch Julie , Kyriakakis Nikolaos , Kumar Satish S , Ajjan Ramzi , Gerrard Georgina , Loughrey Carmel , Glaser Adam , Murray Robert D

Introduction: Childhood-onset brain tumour (CO-BT) survivors demonstrate elevated standardized mortality rates for cardiac disease. Adverse lipid profile and body composition contribute to the increased cardiovascular risk. Little is known about the metabolic changes in long-term survivors of adult-onset brain tumours (AO-BT).Methods: We performed a cross-sectional study to compare cardiovascular risk parameters in CO-BT with AO-BT survivors and healthy ...

ea0038p157 | Neoplasia, cancer and late effects | SFEBES2015

Ultrasound-guided percutaneous ethanol ablation for selected patients with papillary thyroid microcarcinoma: a novel, effective and well tolerated alternative to neck surgery or observation

Hay Ian

Introduction: Perhaps due to a current global epidemic of “overdiagnosis”, papillary thyroid microcarcinoma (PTM) is now the commonest endocrine malignancy (BMJ 348: 3045, 2014). Current management options vary from lobectomy or total thyroidectomy to “active surveillance”. An alternative approach, used successfully for eliminating neck nodal metastases (JCEM 96: 2717, 2011), is ultrasound-guided percutaneous ethanol ablation (UPEA). Here we present our exp...

ea0038p158 | Neoplasia, cancer and late effects | SFEBES2015

Clot structure analysis in survivors of acute lymphoblastic leukaemia: the role of growth hormone deficiency

Kyriakakis Nikolaos , Kumar Satish S , Lynch Julie , Oxley Natalie , Phoenix Fladia , Ajjan Ramzi , Murray Robert D

Introduction: Childhood-onset cancer survivors demonstrate increased mortality rates due to cardiovascular and cerebrovascular events. Studies suggest that leukaemia and brain tumour survivors have a relative risk of 6.4 and 29.0 respectively for stroke. Adverse lipid profile, body composition, insulin resistance and hypertension have been implicated to the increased cardiovascular risk in these patients, however little is known about procoagulant factors and markers of vascul...

ea0038p159 | Neoplasia, cancer and late effects | SFEBES2015

Use of Sunitinib in refractory hypercalcaemia in pancreatic neuroendocrine tumours

Akbarian-Tefaghi Ladan , Wadsley Jonathan , Newell-Price John , Munir Alia

: The orally administered targeted therapies, Sunitinib and Everolimus lengthen progression free survival in pancreatic neuroendocrine tumours (pNETs). Choice of therapy has traditionally been on avoidance of deterioration in established co-morbidities. Sunitinib has been recognised to induce hypocalcaemia and the subsequent need for calcium supplementation has been reported. However, little has been documented about the utility and therapeutic significance of this effect....

ea0038p160 | Neoplasia, cancer and late effects | SFEBES2015

Chromogranin B: a possible prognostic biomarker for neuroendocrine tumours?

Wanigasekara Nipuni E Wanniachchi , Bech Paul , Murphy Kevin

Neuroendocrine tumours (NETs) are rare tumours that originate from neuroendocrine cells and their incidence has increased for the last 20 decades; partly because of advances in diagnostic tools, which have improved detection rates. Chromogranin A (CgA) is the most widely used biochemical tumour marker for NETs, however, its prognostic utility has been questioned due to several non-neuroendocrine causes of elevated CgA. This is the first study to assess the prognostic utility o...

ea0038p161 | Neoplasia, cancer and late effects | SFEBES2015

Imaging and evaluating side effects of antiandrogen therapy

Tommasini-Ghelfi Serena , Dart D Alwyn Dart , Bevan Charlotte

Androgens are required for normal development and fertility. They have a vital role in tissues such as the reproductive tract, the brain, muscle and bone. Prostate cancer (PCa) is the most prevalent malignancy in western males: it is dependent upon circulating androgens and the therapies currently available aim to reduce synthesis of circulating androgens and/or inhibit the pathway using antiandrogens. Therapies inhibiting androgen signalling, and in particular the androgen re...

ea0038p162 | Neoplasia, cancer and late effects | SFEBES2015

Outcome of insulinomas diagnosed in a tertiary endocrine centre

Trifanescu Raluca , Baciu Ionela , Gheorghiu Monica , Dumitrascu Anda , Poiana Catalina

Background: Insulinomas, the most common functional neuroendocrine tumours of the pancreas, are usually sporadic, benign and solitary.Aims: To assess biochemical data, localisation and treatment outcome of insulinomas diagnosed in a tertiary endocrine centre.Patients and methods: Twenty-five patients (14 F/11 M), aged 49.1±14.1 years, diagnosed with insulinoma in a Neuroendocrine Tumours centre between 2000 and 2014 were retro...

ea0038p163 | Neoplasia, cancer and late effects | SFEBES2015

Metastatic paraganglioma with isolated 3-methoxytyramine rise in a patient with SDHC mutation

Alkrekshi Akram , Abhayaratna Sachit , Pitkin Sarah , Dawnay Anne , Baldeweg Stephanie E

59-year-old gentleman with known succinate dehydrogenase complex subunit C (SDHC) gene mutation attended endocrine clinic with non-specific symptoms. Past medical history included glomus jugulare paraganglioma (PGL) surgically treated (1993, 2003) with residual disease, macroprolactinoma treated with cabergoline since 2010, and BPH treated with finasteride and tamsulosin. His brother has glomus vagale. Clinical examination was unremarkable. Plasma metanephrine ranged between 3...

ea0038p164 | Neoplasia, cancer and late effects | SFEBES2015

Recurrent phaeochromocytomas in type2C variant of Von Hippel-Lindau syndrome

Beebeejaun Mehjabeen , Chinnasamy Eswari , Bano Gul

Phaeochromocytomas are rare neuroendocrine tumours with an incidence of 2–8/million persons per year. They occur as a sporadic entity or form part of a complex autosomal dominant familial genetic syndrome, mainly MEN2A, MEN2B, Neurofibromatosis Type1, Von Hippel-Lindau disease (VHL) and mutations in succinyl dehydrogenase. The mean age at diagnosis is in the third decade in the familial cases and the risk of recurrence has been described as high as 23%.<p class="abste...

ea0038p165 | Neoplasia, cancer and late effects | SFEBES2015

Lutetium ablation therapy as treatment for recurrent metastatic bladder paraganglioma

Abhayaratna Sachith , Ojewuyi Taofeek , Gaze Mark , Kar P , Baldeweg Stephanie E

We present the case of a 53 year old gentleman with recurrent bladder paraganglioma. He presented initially in 2010 with headache and blurred vision when passing urine. The tumour was surgically removed, BP normalized and his postoperative MIBG-scan was normal. The patient presented with hypertensive crisis 4 years later with a suspicion of tumor recurrence, confirmed biochemically and radiologically. Treatment with phenoxybenzamine and bisoprolol resulted in adequate BP contr...

ea0038p166 | Neoplasia, cancer and late effects | SFEBES2015

Somatostatin responsive ACTH and precursor excess in a midgut mesentery NET

Dimitriadis G K , Nasoodi A , Khan S , Shatwell W , Chambers L , Tomkins C , Darby C , Gopalakrishnan K , Randeva H S , Murthy N , Weickert M O

Introduction/Background: ACTH production from a midgut mesentery NET is extremely rare (1). A 62y old woman presented with hypokalaemia (2mmol/L) and hyperpigmentation, 11y after surgery of a pT3N1Mx non-functional G1 NET with SRS positive, non-resectable but stable, residual mass encasing mesenteric vessels. Serum cortisol (3261 nmol/L), ACTH (796 ng/L), CgA (530 pmol/L) and urine total cortisol metabolites (33920 μg/24h) including 14 sub-products indicated change of bio...

ea0038p167 | Neoplasia, cancer and late effects | SFEBES2015

Primary adrenal lymphoma

Faruqi Uzma , Kaczmarek Pawel , Ivanov Gleb , Field Benjamin

A 68 year old man presented with shortness of breath and was found to have a pulmonary embolus. During work up of the underlying aetiology he was noted to have bilateral adrenal masses. He was subsequently readmitted with pyrexia and feeling generally unwell. Imaging revealed the progression of adrenal masses and there was biochemical evidence of adrenal insufficiency with a random cortisol at the low end of normal. CT guided biopsy was consistent with the diagnosis of a high ...

ea0038p168 | Neoplasia, cancer and late effects | SFEBES2015

Metastatic bowel carcinoid associated bilateral carcinoid heart disease

Jahagirdar Vidhya R , Kamal Ali D , Steeds Rick , Smith Stacey , Ayuk John

A 63-year-old Caucasian female was admitted with a 12-month history of exertional breathlessness, anxiety attacks, syncopal episodes, diarrhoea, fatigue, reduced appetite, two stones weight loss, and dry facial and truncal flushing. Investigations revealed raised Urine 5-HIAA of 116 (RR <50 μmol/24 h) and raised Chromogranin A of 48 (RR <6 nmol/l). CT scan revealed an extensive soft tissue mass encasing the upper abdominal aorta, compressing the inferior vena cava...

ea0038p169 | Neoplasia, cancer and late effects | SFEBES2015

Familial insulinoma in the absence of MEN

Jeffreys Danielle , Page Georgina , Partridge Helen , Richardson Tristan

Case history: A 42 year old female presented with a history of collapse and seizure activity. Her blood glucose was noted to be 3.1 with the paramedics and subsequent hypoglycaemia was demonstrated on several occasions whilst in hospital. She described a family history of insulinoma in her mother. A 72 h fast was performed as an inpatient to look for insulinoma. The nadir serum glucose was 2.0 mmol/l with an inappropriate C-peptide level of 1006 pmol/l and an insulin level of ...

ea0038p170 | Neoplasia, cancer and late effects | SFEBES2015

A young girl with bilateral adrenal tumours

Koubeh Sakina , Jinadev Pushpa , Alhelfi Moayed , Davis Julian

18 year old female referred with 2 years history of hirsutism and secondary amenorrhoea. She was born at 37 weeks and was found to have neonatal hypothermia, hypoglycaemia and crossed hemihypertrophy, but no macroglossia. Due to the increased risk of Wilm’s tumour she had regular ultrasound scans up to the age of 11 years. She attained menarche at the age of 13 but had only two periods within 18 months. By the age of 15 she developed hirsutism and acne. Biochemistry revea...

ea0038p171 | Neoplasia, cancer and late effects | SFEBES2015

Acromegaly in association with a bronchial carcinoid tumour

Rys Andrzej , Smith Jamie

Bronchial carcinoid tumours are uncommon pulmonary neoplasms. Manifestation of a bronchial carcinoid with acromegaly secondary to extra-pituitary growth hormone releasing hormone (GHRH) production is rare, but bronchial carcinoid tumours are the most common cause of ectopic GHRH secretion.We report the case of 60 year old female, ex-smoker with hypertension presenting with cough, dyspnoea and right lower lobe opacity on the chest X-ray. Patient was noted...

ea0038p172 | Neoplasia, cancer and late effects | SFEBES2015

Challenges in the diagnosis and management of a case of glucagonoma first presenting as a localised genital rash

Hunt Frances , Raza Farheen , Ndip Agbor , Chattington Paula

Introduction: Glucagonoma syndrome is a rare paraneoplastic phenomenon characterised by necrolytic migratory erythema, diabetes mellitus and symptoms of gastrointestinal upset. It is often diagnosed late leading to a poor prognosis.Case report: A 70 year old lady with type two diabetes mellitus and fibromyalgia presented in late 2011 to Gynaecology with an itchy erythematous vulval rash. Skin biopsy suggested lichen sclerosis and she was discharged with ...

ea0038p173 | Neoplasia, cancer and late effects | SFEBES2015

A management dilemma – emergency treatment of primary hyperparathyroidism in suspected but unconfirmed multiple endocrine neoplasia type 1

Khurana Ramneet , Gandhi Ashu , Issa Basil

A 27 year old male patient with severe cardiomyopathy secondary to Epirubicin chemotherapy for rhabdomyosarcoma in infancy was noted to be hypercalcaemic during the course of admission for severe inotrope dependant congestive cardiac failure. Biochemical investigations confirmed a diagnosis of primary hyperparathyroidism (corrected Calcium 3.10 mmol/l, PTH 22 pmol/l, Vitamin D 77 nmol/l).His brother had undergone trans-sphenoidal pituitary surgery for ac...

ea0038p174 | Neoplasia, cancer and late effects | SFEBES2015

Promoter methylation signatures of BRCA2 and TP53 genes in the serum of some breast cancer patients attending radiotherapy clinic in Lagos, Nigeria

Samuel Titilola , James Babatunde , Adara-Ali Ahmed , Fayoda Yetunde , Habeeb Mym

The prevalence of new cases of cancer in developing countries even though less than the developed countries have greater mortality rate, due to lack of access to treatment and early detection of the disease. Epigenetic alterations in BRCA2 and TP53, such as DNA methylation, maybe an effective approach in diagnosis, prognosis and therapy in breast cancer. This study examines the DNA methylation signature of BRCA2 and TP53 in Nigerian breast cancer patients. In this study, thirt...

ea0038p175 | Neoplasia, cancer and late effects | SFEBES2015

Confusion in a patient with carcinoid syndrome

Aarella Vikram , Dix Hannah , Lee Stuart

A 64 year old lady was admitted with a 2 day history of feeling generally unwell. Her relatives also reported new onset confusion over these 2 days. Her bloods showed raised inflammatory markers (CRP 110.3 mg/l, WCC 18.2×109/l) hypoalbuminemia (17 g/l), bilirubinemia (55 μmol/l) and a raised alkaline phosphatase (917 IU/l). She had recently been diagnosed with carcinoid syndrome; primary tumour situated in the terminal ileum with liver metastasis and had b...