Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2013

Poster Presentations

Neoplasia, cancer and late effects

ea0031p149 | Neoplasia, cancer and late effects | SFEBES2013

Epigenetic modifiers reduce proliferation of human neuroendocrine tumour cell lines

Lines Kate E , Gaynor Katherine U , Stevenson Mark , Newey Paul J , Piret Sian E , Filippakopoulos Panagis , Muller Susanne , Grozinsky-Glasberg Simona , Grossman Ashley B , Knapp Stefan , Schofield Christopher , Bountra Chas , Thakker Rajesh V

Neuroendocrine tumours (NETs), occurring at multiple sites including the pancreas, gastrointestinal tract, lung, thymus and pituitary, usually present at an advanced metastatic stage, and are increasing in incidence and prevalence as awareness and diagnostic techniques have improved. Treatments for NETs including surgery, drugs (e.g. somatostatin analogues), chemotherapy, radiotherapy and radionuclide therapy, are often not effective and as such additional therapeutic agents a...

ea0031p150 | Neoplasia, cancer and late effects | SFEBES2013

POMC correlates with viable tumour cell mass in lung cancer xenografts

Bryant Jennifer

Small cell lung cancer (SCLC) is the most common cause of the ectopic ACTH syndrome and is characterised by rapid growth and poor prognosis. In the ectopic ACTH syndrome, tumours secrete highly elevated levels of the ACTH precursor, proopiomelanocortin (POMC), compared to ACTH itself (Oliver 2003). This study aimed to develop a mouse model of SCLC capable of secreting high levels of POMC and correlate this with viable tumour mass to assess POMC as a potential biomarker.<p ...

ea0031p151 | Neoplasia, cancer and late effects | SFEBES2013

Phenotype–genotype analysis in a cohort of patients with multiple endocrine neoplasia type 1 identifies a novel nonsense mutation at codon 554

Reddy Snigdha , Goudie Calum , Parker Victoria , Park Soo-Mi , Treacy Becky , Simpson Helen

Aims: MEN1 is characterised by parathyroid, pituitary and pancreatic tumours in association with neoplasia of intra-thoracic endocrine tissue, adrenal glands and cutaneous manifestations. Mutations of the tumour suppressor Menin are causative and affected patients possess heterozygous germline mutations in MEN1, with acquisition of a second hit in the wild-type allele initiating tumourigenesis. Phenotype–genotype correlations can provide insights into the molecular functi...

ea0031p152 | Neoplasia, cancer and late effects | SFEBES2013

Parathyroid gland studies in mouse models for endocrine tumours defines anatomical locations and ultrastructural differences between normal and tumour cells

Walls Gerard , Clark Anne , Thakker Rajesh

Investigation of parathyroids in mouse models is hampered by difficulties in identifying the small glands. We developed a microsurgical technique to identify murine parathyroids by dissecting from the distal thyrothymic ligament to the lower thyroid pole (LTP). Parathyroids were identified in 100 mice which comprised: 48 mice deleted for a cell-division-cycle 73 gene allele (Cdc73+/−), involved in the hyperparathyroidism-jaw tumour syndrome; ...

ea0031p153 | Neoplasia, cancer and late effects | SFEBES2013

Functional induction of the oestrogen-regulated PTTG1-binding factor in colorectal cancer

Kwan Perkin , Read Martin , Seed Robert , Ryan Gavin , Smith Vicki , Watkins Rachel , Lu Wenli , Ward Stephen , Watkinson John , Franklyn Jayne , Boelaert Kristien , McCabe Christopher

PTTG1-binding factor (PBF) is an oestrogen-regulated proto-oncogene that is overexpressed in thyroid, breast and pituitary tumours. The precise role of PBF in tumourigenesis, however, has not been established, nor whether it is also an aetiological factor in non-endocrine cancer. In this study, we investigated PBF function in established colorectal cells and human tumours. Specific binding was evident between the tumour suppressor p53 and both endogenous and exogenous PBF in H...

ea0031p154 | Neoplasia, cancer and late effects | SFEBES2013

PBF overexpression causes increased p53 ubiquitination and degradation via MDM2

Ryan Gavin , Read Martin , Seed Robert , Smith Vicki , Fong Jim , Turnell Andrew , Franklyn Jayne , McCabe Christopher , Boelaert Kristien

The pituitary tumor-transforming gene-binding factor (PBF) is a relatively uncharacterised proto-oncogene, which is overexpressed in thyroid tumours. PBF elicits tumor growth in nude mice, whilst thyroid targeted transgenic overexpression in the PBF-Tg mouse induces hyperplasia and macrofollicular lesions, accompanied by induction of the E2 ubiquitin ligase Rad6. Our previous unpublished data showed that PBF binds to p53, and reduces stimulation of downstream target genes by c...

ea0031p155 | Neoplasia, cancer and late effects | SFEBES2013

Mechanisms of estrogen receptor function in breast cancer

Carroll Jason

Estrogen receptor (ER) is the defining feature of luminal breast cancers, where is functions as a transcription factor in response to the ligand estrogen. The traditional view of ER getting recruited to promoters of target genes is too simplistic. The recent discovery of ER–DNA interaction regions from ER+ breast cancer cell lines has revealed that ER rarely associates with promoter regions of target genes and instead associates with enhancer elements significant distance...

ea0031p156 | Neoplasia, cancer and late effects | SFEBES2013

Investigation of the antiproliferative effect of natural sesquiterpene lactones on human cancer cell lines

Molnar Judit , Lajter Ildiko , Hajdu Zsuzsanna , Szekeres Thomas , Saiko Philipp , Hohmann Judit , Zupko Istvan

Plants and plant extracts play a crucial role in the research of novel antineoplastic agents. Five sesquiterpene lactones, 4β,15-dihydro-3-dehydrozaluzanin C (ddZC), zaluzanin C, artecanin, 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide and iso-secotanapartholide methyl ether were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). MTT-assay was used to det...

ea0031p157 | Neoplasia, cancer and late effects | SFEBES2013

Predicted NES in PBF appears to be functional in vitro

Poole Vikki , Smith Vicki , Ryan Gavin , Gilligan Lorna , Seed Robert , Sharma Neil , Read Martin , Boelaert Kristien , McCabe Christopher

Pituitary tumor transforming gene (PTTG) binding factor (PBF) is a proto-oncogene which is frequently upregulated in endocrine cancers. PBF has previously been determined to contain several putative signal sequences within its 180 amino acids. Previous studies have shown the nuclear localisation signal (NLS) to be functional and prediction software now suggests the presence of a putative leucine-rich nuclear export signal (NES) between residues 17 and 27. PBF is known to shutt...

ea0031p158 | Neoplasia, cancer and late effects | SFEBES2013

Pituitary metasases: patients presenting with cranial nerve palsies and diabetes insipidus: a single centre experience

Salaris Paola , Kordbacheh Tiana , Whitelaw Ben , Mustafa Omar , Visca Anna , Thomas Nick , Bullock Peter , Barazi Sinan , Landau David , King Andrew , Hampton Timothy , Gilbert Jackie , McGregor Alan , Aylwin Simon

Background: Pituitary metastases are a rare complication of systemic malignancy. The most common presentations of pituitary masses include visual field defects, headaches, and hypopituitarism, but cranial nerve palsies and diabetes insipidus are also recognised although unusual. We aimed to determine if these were more frequently associated with pituitary metastasis.Methods: We conducted a review of 944 patients undergoing pituitary surgery from a teachi...

ea0031p159 | Neoplasia, cancer and late effects | SFEBES2013

The relationship between anatomical location of phaeochromocytoma and paraganglioma and their secretory properties

Lim Chung Thong , Gill Jasdeep , Ramachandran Radha , Brook Susan E , Martin Niamh M , Dhillo Waljit , Todd Jeannie , Palazzo Fausto , Caplin Martyn , Bouloux Pierre , Meeran Karim , Tan Tricia , Khoo Bernard

Background: Phaeochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumours that can secrete catecholamines. PCC are found in the adrenals, whereas PGL are found at any level between the skull base to the pelvis. More than 25% of cases are associated with mutations in susceptibility genes such as the SDH subunits. Screening for PCC/PGL crucially depends on detection of biochemical markers such as catecholamines and metanephrines (catecholamine metabolites).<p ...

ea0031p160 | Neoplasia, cancer and late effects | SFEBES2013

Adjuvant use of 131I-MIBG in phaeochromocytoma and paraganglioma at high risk of malignancy

Rutherford Matthew A , Rankin Alastair , Yates Michael , Reed Nicholas , Freel E Marie

Phaeochromocytomas (Phaeo) and paragangliomas (PGL) are rare catecholamine producing tumours. It can be difficult to predict their malignant potential and patients can sometimes present with metastatic disease many years after their original diagnosis (1). Therefore, we offer a single dose of adjuvant 131I-Metaiodobenzylguanidine (131I-MIBG) to subjects felt to be at higher risk of local recurrence (demonstration of capsular or vascular invasion on pathol...

ea0031p161 | Neoplasia, cancer and late effects | SFEBES2013

Multi-modal approach to treatment in advanced adrenocortical carcinoma

Hall Lesley , Reed Nick , Leen Edward , Wasan Harpreet , Perry Colin , Freel Marie

A 38-year-old lady, who was 9 months post-partum, presented in 2008 with hirsutism, acne and abdominal discomfort. She was virilised and had an easily palpable right upper quadrant mass. Biochemistry revealed mild hypokalaemia (K 3.3 mmol/l), low albumin and gross elevation of serum androgens (androstenedione 93.9 nmol/l, DHAS 37.7 μmol/l and testosterone 13.7 nmol/l). UFC was 380 nmol/24 h but following 1 mg dexamethasone, cortisol suppressed fully. Urine steroi...

ea0031p162 | Neoplasia, cancer and late effects | SFEBES2013

Prevalence of multiple endocrine neoplasia type 1 syndrome in primary hyperparathyroidism

Kota Sunil Kumar , Meher Lalit Kumar , Jammula Sruti , Modi Kirtikumar D

Objective: To assess the prevalence of multiple endocrine neoplasia type 1 (MEN1) in patients with symptomatic primary hyperparathyroidism (PHPT).Methods: A retrospective analysis of 75 consecutive patients with symptomatic PHPT from January 1994 to July 2012 was done, who underwent parathyroid surgery at our centre. Five patients had MEN1 syndrome. Among them one was familial MEN1. The patients with MEN1 were analyzed based on clinical presentation, bio...

ea0031p163 | Neoplasia, cancer and late effects | SFEBES2013

Primary thyroid cancer as late effects of childhood cancer therapy: a case series of five patients

Kenchaiah Manohara , Naing Aye , Sennik Devesh , Bano Gul

Introduction: Advancement in modalities of treatment in childhood malignancies has improved the survival. Though Hypothyroidism is the first recognised and commonest thyroid disease in these set of patients, there is also an increased risk of subsequent primary thyroid cancer among the Survivors childhood malignancies who have had radiotherapy to the head, neck, or upper thorax. We hereby present case series of five patients who developed thyroid cancer after childhood cancer ...

ea0031p164 | Neoplasia, cancer and late effects | SFEBES2013

Diagnosis, localisation and management of insulinoma; a single-centre experience

Powlson Andrew S , Challis Benjamin , Curran Suzanne , Jah Asif , Praseedom Raj , Huguet Emmanuel , Jamieson Neville , Metz Andrew , Carroll Nicholas , Shaw Ashley , Halsall David , Gurnell Mark , Krishna Chatterjee V , Simpson Helen L

Nineteen cases of insulinoma were treated in this centre between 2003 and 2012 (12 female, 7 male, 5 associated with MEN-1). Of the cohort, 14 had their primary investigation and management here. All presented with symptoms consistent with hypoglycaemia and had a supervised fast demonstrating serum glucose <2.2 mmol/l with inappropriately normal/elevated insulin.11 of 14 patients proceeded to surgery. Two elderly patients declined further investigati...

ea0031p165 | Neoplasia, cancer and late effects | SFEBES2013

Audit of patients with multiple endocrine neoplasia type 1 in a tertiary referral centre

Goudie Calum , Reddy Snigdha , Parker Victoria , Curran Suzanne , Corrie Pippa , Shaw Ashley , Jamieson Neville , Praseedom Raaj , Huget Emmanuel , Jah Asif , Carroll Nicolas , Buscombe John , Park Soo-Mi , Simpson Helen

Aim: To review the presentation, management and outcomes in adult patients with MEN1 attending a multidisciplinary clinic.Methods: Case notes and electronic records were reviewed in patients attending a tertiary centre clinic for care of MEN1.Results: Forty-eight patients were analysed; 46% were male and 54% female. Mean age was 49 years (range 14–89) and 4% were deceased. Eighty-five percent had confirmed MEN1 mutations and 2...

ea0031p166 | Neoplasia, cancer and late effects | SFEBES2013

Difficulties in management of malignant insulinoma

Garg A , Rathore A M , Patel D C , Khoo B , Caplin M , Meyer T

Introduction: Insulinomas are the most common, functioning, pancreatic neuro-endocrine tumours. The minority of patients <10% who present with metastatic disease have a median survival of <2 years.We present a case of a gentleman with a 30 years history of Multiple Endocrine neoplasia type 1 (MEN1), which highlights the various modalities of treatment and the challenges from his progressive disease and marked symptomatic hypoglycaemia.<p clas...

ea0031p167 | Neoplasia, cancer and late effects | SFEBES2013

Crizotinib induced hypogonadism: a novel complication of lung cancer treatment

Lu Shir Kong , Htay Thein , Popat Sanjay , Morganstein Daniel

Tyrosine kinase inhibitors and other targeted treatments are revolutionizing the treatment of cancer. However multiple endocrine side effects of these treatments are emerging.Crizotinib, a multi-targeted small molecule tyrosine kinase inhibitor of ALK and c-met, has been approved by the FDA for the treatment of non small cell lung cancer (NSCLC) patients with a novel oncogenic gene fusion, EML4-ALK and its variants. Crizotinib is generally well tolerated...

ea0031p168 | Neoplasia, cancer and late effects | SFEBES2013

Review of patients with adrenocortical carcinoma at a tertiary referral centre

Deshpande S , Parker V , Ahmed U , Moore D , Jamieson N V , Gurnell M G , Chatterjee V K , Basu B , Corrie P , Simpson H L

Introduction: Adrenocortical carcinoma (ACC) is a rare but devastating malignancy. We performed a review to determine outcome in our patient cohort.Of 20 patients 14 were females, six males. Median overall survival was 27.5 months (range 1–168), nine being deceased. Mean age at presentation 52.3 years (range 18–71). The majority of cancers were large; 5% ≤5 cm, 40% 5–10 cm, 55 >10 cm. 25% had stage IV disease, 10% stage III, 55% ...

ea0031p169 | Neoplasia, cancer and late effects | SFEBES2013

Between genetics, guidelines and treatment in MEN2A: a family affair

Dobrescu Ruxandra , Hortopan Dan , Stanescu Bogdan , Radian Serban , Badiu Corin

The multiple endocrine neoplasia syndrome type 2A (MEN 2A) is the consequence of a heritable mutation in the RET proto-oncogene, leading to a very high predisposition to develop medullary thyroid carcinoma (MTC), pheochromocytoma and primary parathyroid hyperplasia. Screening of ‘at-risk’ family members and prophylactic thyroidectomy is recommended – but not always easily accomplished.Our proband was diagnosed with MTC in 1977 (at age 21),...

ea0031p170 | Neoplasia, cancer and late effects | SFEBES2013

Cowden syndrome

Naing Aye , Kenchaiah Manohar , Bano Gul , Hodgson Shirley

A 27-year-old lady presented with headache, bilateral papilloedema and long standing thyroid enlargement. Her MRI brain showed a cerebellar lesion. She had surgery and histology was consistent with Lhermitte–Duclos, a benign brain tumour. She also had retinal changes. Her fluroscein angiogram and optical coherence tomography showed multiple retinal harmatomas and pigmented retinal epithelium. She had retrosternal thyroid extension and had total thyroidectomy because of tr...

ea0031p171 | Neoplasia, cancer and late effects | SFEBES2013

Recurrent bronchial carcinoid tumour presenting as a thyroid nodule

Hall Lesley , Smith Chris , Carty David , McManus Frances , Reed Nick , Freel Marie , Perry Colin

A 38-year-old lady presented in 2003 with a 2 years history of recurrent pneumonia, with CXR having demonstrated intermittent right lower zone consolidation. CT of chest revealed dense right lower lobe consolidation and a 2.5 cm tumour occluding the right lower lobe orifice was found on bronchoscopy. Strongly positive immunohistochemical staining for chromogranin, NCAM, PGP 9.5 and synaptophysin suggested carcinoid so right lower and middle lobectomy was performed. Histology c...

ea0031p172 | Neoplasia, cancer and late effects | SFEBES2013

Gut carcinoid in a patient with horseshoe kidney and family history of carcinoid syndrome: a case report

Lois Konstantinos , James Andy , Perros Petros

Introduction: The familial risks of carcinoids are not clear. There has never been a report of gastrointestinal carcinoid coexisting with horseshoe kidney.Case presentation: We present the case of a 15 mm well differentiated metastatic small bowel NET with vascular and perineural invasion and three of four positive lymph nodes (Ki67: 1.9%, ENETS stage: pT4 pN1 pMX R1) in a 75-year-old British male with episodes of diarrhea and 24 h urinary 5HIAA: 48 (&#6...

ea0031p173 | Neoplasia, cancer and late effects | SFEBES2013

Insulinoma in postprandial hypoglycaemia and aggressive behaviour

Pan Shwe Zin Chit , Mathews Anitha

Background: Fasting hypoglycaemia is a common presenting symptom of insulinoma. However, insulinoma should be considered as a potential cause in those presenting with symptoms of hypoglycaemia after meal (1, 2, 3). Here we report a case who initially presented with postprandial symptoms though there was evidence of fasting hypoglycaemia subsequently.Case report: A 57-year-old lady initially presented with a 2 years history of palpitation, feeling hot, sw...

ea0031p174 | Neoplasia, cancer and late effects | SFEBES2013

Hyperparathyroid jaw tumour syndrome

Kumar Pranav , Jones Keston

Hyperparathyroid Jaw tumour syndrome is a familial form of primary hyperparathyroidism. Individuals are predisposed to develop parathyroid carcinomas (15%), ossifying fibromas of mandible and maxilla (30%), renal abnormalities including cystic lesions and hamartomas, and uterine tumours (1, 2). The pathogenic mutation is in CDC73 gene (previously known as HRPT2 and C1orf28) inherited in an autosomal dominant manner.Our patient was the first person in the...