Endocrine Abstracts

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...

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...

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...

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...

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...

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 ...

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...

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...