Endocrine Abstracts

Attempts at restoring endogenous insulin secretion by the transplantation of human islet tissue, initially using whole pancreas transplantation, was first reported in 1966. Although there is also a long history surrounding the transplantation of isolated human islets, it was the development and subsequent publication of the Edmonton, glucocorticoid free immunospressive regimen, in 2000, that transformed the use and availability of islet cell transplantation for people with dif...

Autoimmune thyroid disease (AITD) is the commonest of the autoimmune disorders. Strong familial clustering supports a hereditary component to the development of disease. However, the pattern of inheritance suggests that many genes with relatively small effect size are contributing to the genetic architecture of both Graves’ disease and autoimmune hypothyroidism. Whilst early candidate gene studies helped to identify some of the major effects conferring risk to AITD, inclu...

Autoimmune thyroid disease (AITD) clusters in families pointing, at least in part, to a genetic basis for disease. Subjects with AITD and other family members also have an increased risk for the development of other autoimmune diseases such as type 1 diabetes (TID) and rheumatoid arthritis suggesting the involvement of general autoimmunity genes. In common with other autoimmune diseases the HLA region was the first cluster of genes to be reported to be associated with AITD. Mo...

Graves' disease (GD) is an autoimmune disorder of the thyroid gland, of which the aetiology is unknown, but susceptibility to disease is thought to result from both genetic and environmental factors. Familial clustering data suggests that GD is a polygenic disorder, with laboratory studies identifying the HLA gene region and the CTLA-4 gene region as susceptibility loci. However, together the HLA region and the CTLA-4 gene regions only contribute about 50% towards the genetic ...

Genome wide association (GWA) studies have revolutionised the search for new susceptibility loci for complex diseases such as Graves’ disease (GD), by confirming association of known genes and identifying several novel susceptibility loci. The high density lipoprotein binding protein (HDLBP) on chromosome 2q37 is one such novel locus recently identified by the WTCCC as part of a 14 500 nonsynonymous single nucleotide polymorphisms (SNP) screen performed in 900 UK C...

Background: Measurement of urinary cortisol is commonly used in the investigation of suspected Cushing’s Syndrome and is most often performed using immunoassay. This approach exhibits significant assay variability necessitating the use of method specific reference ranges. A reference range for cortisol nmol/L: creatinine mmol/L ratio is reported based on the results from 104 early morning urine samples collected from healthy individuals and analysed using the AutoDelfia A...

We have previously (Allehabadia et al., JCEM, 2001) reported better cure rates for patients treated with a single fixed dose of 370 MBq 131I compared with 185 MBq. We have since increased the standard dose of administered radioiodine to 600 MBq and re-audited our data in 1240 consecutive thyrotoxic patients. We aimed to compare the efficacy of the new dose regimen and to explore factors that might predict outcome. Patients were categorised in 3 diagnostic gro...

Graves’ disease (GD) is an autoimmune disorder of the thyroid gland. Autoimmune diseases cluster within families and individuals, leading to the hypothesis of common autoimmunity genes being shared between diseases. This has been confirmed through studies demonstrating association of the HLA region, the CTLA-4 gene and the PTPN22 gene with many disorders including GD and rheumatoid arthritis (RA). We and others have confirmed highly significant association of the R620W SN...

The HLA class II region, in particular DRB1/DQA1/DQB1, has been consistently associated with Graves’ disease (GD) for over thirty years. Only recently has work within our own group made progress in narrowing down the etiological variant(s) present within DRB1/DQA1/DQB1, by excluding DQB1, and by mapping association at DRB1 to nine amino acid positions present within the peptide binding domain, with position β74 being the most associated. Independ...

The HLA class II region, CTLA-4 and PTPN22, have been consistently associated with autoimmune disease (AID). Recently, three DNA variants, two of which (M55V and 001Msp) are present in NF-κB inhibitors SUMO-4 and MAP3K7IP2, and one of which (fcrl3_3) modulates NF-κB binding and production of the B cell surface molecule FCRL3, have been reported to be associated with a number of AIDs. The aim of this study was to investigate genetic variati...