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24th Joint Meeting of the British Endocrine Societies

Oral Communications

Oral Communication 5: Thyroid

ea0009oc34 | Oral Communication 5: Thyroid | BES2005

Association between serum TSH and fT4 concentrations and occurrence of atrial fibrillation in a large community-based population of elderly subjects. The Birmingham Elderly Thyroid Study (BETS)

Gammage M , Parle J , Franklyn J , Wilson S , Roberts L , Holder R , Sheppard M , Hobbs F , Roalfe A , Heath C , Pattison H

We conducted a prospective study of 5784 subjects aged 65 or over, screened and identified in primary care. The cohort comprised 2934 women, 2850 men, mean age 73.5 years (range 63.5-98.6). All had TSH measured in a sensitive assay (normal range 0.4-5.5 mU/l), as well as free T4 (normal range 9-20 pmol/l), and resting 12-lead ECG. Atrial fibrillation (AF) was present in 4.81% of the cohort. The prevalence of AF showed significant variation with serum TSH concentrations, being ...

ea0009oc35 | Oral Communication 5: Thyroid | BES2005

Risk of second cancers among people with thyroid cancer - treatment effects or common aetiology?

Sandeep T , Strachan M , Reynolds R , Brewster D , Scelo G , Pukkala E , Hemminki K , Anderson A , Tracey E , Friis S , McBride M , Kee-Seng C , Pompe-Kirn V , Kliewer E , Tonita J , Jonasson J , Martos C , Boffetta P , Brennan P

BackgroundIncreasing incidence of thyroid cancer together with improved prognosis raises a concern regarding development of second primary cancers. Moreover, little is known about the incidence of thyroid cancer as a second primary neoplasm after other cancers.MethodsA cohort of 39002 people (356034.5 person years) with primary thyroid cancer was identified in 13 population-based cancer registries in Europe, ...

ea0009oc36 | Oral Communication 5: Thyroid | BES2005

PTTG Induces Genomic Instability in Thyroid Cells

Kim D , Stratford A , Boelaert K , Pemberton H , Gockce C , Eggo M , Tannahill L , Watkinson J , Franklyn J , McCabe C

Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Differentiated thyroid cancers exhibit aneuploidy; cytogenetic studies have demonstrated the importance of genetic instability in thyroid cancer development. Pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and over-exp...

ea0009oc37 | Oral Communication 5: Thyroid | BES2005

PTTG Binding Factor (PBF) - a novel transforming gene in thyroid tumorigenesis which represses iodide uptake

Stratford A , Boelaert K , Tannahill L , Eggo M , Gittoes N , Franklyn J , McCabe C

We have previously shown PTTG binding factor (PBF) to be a transforming gene both in vitro and in vivo, forming colonies in soft agar and tumours in nude mice. We have found that along with PTTG, PBF is upregulated in thyroid cancer and is also a prognostic indicator for recurrence. As our cohort of thyroid cancers showed significantly reduced sodium iodide symporter (NIS) expression compared to normal thyroid (47% reduction, N=27, P=0.005), which was negatively ...

ea0009oc38 | Oral Communication 5: Thyroid | BES2005

Anti-TNFa therapy inhibits TNFa-dependent ICAM1 up-regulation in orbital fibroblasts from patients with thyroid associated ophthalmopathy

Cawood T , Moriarty P , Golden-Mason L , O'Farrelly C , O'Shea D

Thyroid Associated Ophthalmopathy (TAO) is an autoimmune inflammatory condition that usually occurs in patients with Graves' disease. Current treatment for TAO is inadequate and anti-cytokine agents may represent a potential new therapeutic strategy. Orbital fibroblasts are central to the disease mechanism, and have been shown by immunohistochemisty to up-regulate adhesion molecule ICAM1 expression in response to certain cytokines including TNFalpha.In t...

ea0009oc39 | Oral Communication 5: Thyroid | BES2005

Thyrotropin receptor (TSHR) activation in preadipocytes stimulates the early but inhibits the terminal stages of adipogenesis

Janus D , Baker G , Fuhrer D , Ludgate M

The TSHR is expressed during adipogenesis. We have employed in vitro models to investigate how TSHR activation affects this process. Gain-of-function TSHR mutants were introduced into preadipocytes using retroviral vectors. We have demonstrated that TSHR activation inhibits their proliferation and PPAR-gamma agonist (pioglitazone) induced adipogenesis. The aim of this study was to investigate the mechanisms operating.Non-modified primary human preadipocy...

ea0009oc40 | Oral Communication 5: Thyroid | BES2005

Development of novel thyroid stimulating monoclonal antibodies from an experimental model with potencies equivalent to those in Graves' disease patients, including full agonistic activity but also differential blocking properties

Gilbert J , Rao P , Salehi S , Gora M , McGregor A , Banga J

In Graves' disease (GD), it is recognised that isolation of the rare pathogenic autoantibodies that stimulate the thyrotropin receptor (TSHR) would assist in understanding disease pathogenesis. To date, monoclonal antibodies (mabs) to the TSHR with thyroid stimulating activity (TSAbs) have been isolated from experimental models of GD which are 100 fold weaker than the reported single human mab with strong TSAb activity. We describe two novel IgG mabs from a murine model of GD ...