Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2010

Oral Communications

Steroids and thyroid

ea0021oc5.1 | Steroids and thyroid | SFEBES2009

Familial GC resistance: a novel, naturally occurring mutation which has dominant negative effects on ligand-dependent and -independent GR action

Trebble P , Matthews L , Blaikley J , Wayte A , Black G , Wilton A , Ray D

Glucocorticoids (GCs) are the most potent anti-inflammatory agents known and are used extensively in the treatment of inflammatory disease, however an individuals response to therapy varies greatly. Resistance to GC is often attributed to mutations within the glucocorticoid receptor (GR) through which GC elicit their effects. Here, we present a kindred with GR haploinsufficiency yet no clinical phenotype. PCR and GR sequence profiling of genomic DNA isolated from patient blood...

ea0021oc5.2 | Steroids and thyroid | SFEBES2009

De novo cortisol synthesis by primary human keratinocytes

Hannen Rosalind , Michael Anthony , Burrin Jacky , Philpott Micheal

Cortisol-based therapy is still the most potent anti-inflammatory treatment available for skin conditions such as psoriasis and atopic dermatitis. Previous studies have demonstrated the presence of components of the steroidogenic pathway in keratinocytes, though surprisingly none have reported that these cells, which form up to 90% of the epidermis are able to synthesise cortisol1,2. Here, we demonstrate that primary human keratinocytes (PHK) are capable of de no...

ea0021oc5.3 | Steroids and thyroid | SFEBES2009

Differential roles of PAPSS1 and PAPSS2 in the control of androgen synthesis

McNelis Joanne , Idkowiak Jan , Nogueira Edson , Ward Alexandra , Dhir Vivek , Arlt Wiebke

A key component of androgen synthesis is the availability of the pro-hormone DHEA, which is either converted to active androgens or inactivated to its sulfate ester DHEAS by DHEA sulfotransferase (SULT2A1). The latter reaction requires provision of the universal sulfate donor 3′-phosphoadenosine-5′-phosphosulfate, PAPS. In humans, PAPS is generated by the PAPS synthase isoforms PAPSS1 and PAPSS2. Recently, inactivating PAPSS2 mutations have been identified i...

ea0021oc5.4 | Steroids and thyroid | SFEBES2009

Induction of hypothyroidism with radioactive iodine therapy is associated with improved survival in patients with hyperthyroidism

Boelaert Kristien , Maisonneuve Patrick , Torlinska Barbara , Franklyn Jayne

Hyperthyroidism is known to result in excess all-cause and circulatory mortality. We set out to identify which factors predict mortality in 1290 patients (1019 females and 271 males) with overt hyperthyroidism and determined if treatment with antithyroid drugs or radioactive iodine (131I) affect outcome. All individuals were aged ≥40 years (median: 57.5 years) and presented to our clinic between 1989 and 2003. Cause of death was compared with age- and period s...

ea0021oc5.5 | Steroids and thyroid | SFEBES2009

Akt activation in a murine thyroid goitre model induced by the tumourigenic factor PBF

Read Martin , Lewy Greg , Sharma Neil , Fong Jim , Smith Vicki , Seed Robert , Kwan Perkin , Leadbeater Wendy , Warfield Adrian , Watkinson John , Franklyn Jayne , Boelaert Kristien , McCabe Chris

PTTG binding factor (PBF) is a poorly characterised transforming gene that is overexpressed in thyroid tumours and inhibits the activity of the sodium iodide symporter (NIS) in vitro. Our recent investigations demonstrated that PBF mRNA expression was 2.6-fold higher in thyroid tissue excised from patients with multinodular goitres (MNG) than in normal thyroid tissue (n=25, P<0.01). We have now generated a murine transgenic model of targeted overexpres...

ea0021oc5.6 | Steroids and thyroid | SFEBES2009

Is it safe for patients taking thyroxine to have a low but not suppressed serum TSH concentration?

Leese Graham , Flynn Robert

For patients taking thyroxine replacement guidelines generally recommend aiming for a target TSH within the laboratory reference range. The evidence for this guidance is generally based on an extrapolation of data from patients with endogenous subclinical thyroid disease. We aimed to examine the safety of having a TSH which was either suppressed (≤0.03 mU/l), low (0.04–0.4 mU/l), ‘normal’ (0.4–4.0 mU/l) or raised (>4.0 mU/l) in a population-based ...

ea0021oc5.7 | Steroids and thyroid | SFEBES2009

X chromosome inactivation: the key to the female preponderance in Graves' disease?

Simmonds Matthew , Newby Paul , Jackson Laura , Hargreaves Chantal , Brand Oliver , Carr-Smith Jackie , Franklyn Jayne , Gough Stephen

Graves’ disease (GD) affects >2% of the population and occurs more frequently in females than males. Several hypotheses have been put forward to explain the female preponderance including increased immune responsiveness, gonadal steriods, sex chromosome susceptibility loci and, more recently, skewed X inactivation (XCI). XCI occurs in females causing one of their X chromosomes to be randomly inactivated enabling dosage compensation with males who only have one copy of...

ea0021oc5.8 | Steroids and thyroid | SFEBES2009

The effect of genetic variation in PDE8B and DIO1 on thyroid hormone levels

Taylor Peter , Panicker Vijay , Iqbal Ahmed , Timpson Nicholas , Walsh John , Dayan Colin

Background: Single-nucleotide polymorphisms (SNPs) allow us to study effects of genetic variation on thyroid hormone levels. Phosphodiesterase 8B (PDE8B) is a protein responsible for cAMP generation, found in thyroid and brain tissue, but not normal pituitary tissue. Variation at this locus has been reported to influence TSH levels, but its effect on T3 and T4 had not been studied in the general population. Deiodinase 1 (DIO1) is known to influence T...