Endocrine Abstracts

In recent years measurement of steroid hormones like testosterone, androstenedione, cortisol, and cortisone has become increasingly important in both patient care and research. This is mainly due to the simple and non-invasive sample collection. We investigated in twenty healthy volunteers whether there is a difference between steroid hormone concentrations in unstimulated and parotid gland saliva as well as stimulated saliva collected while chewing without aid, using cotton a...

Empagliflozin is a potent, highly selective sodium glucose cotransporter-2 inhibitor in development for treatment of type 2 diabetes mellitus. This randomized, placebo-controlled, double-blind study assessed the effects of empagliflozin on the QT interval. Thirty healthy subjects (14/16 female/male; mean [range] age 34.5 [18–52] years) received single doses of 25 mg (within therapeutic range) and 200 mg (supratherapeutic) empagliflozin and 400 mg moxifloxacin as positive ...

Genome wide association screening (GWAS) has proved invaluable in determining otherwise undetected genetic effects for several common endocrine diseases. The largest GWAS performed in Graves’ disease (GD), to date, has not only confirmed association of several known gene regions, including the HLA region, TSHR and FCRL3, but has also identified several other possible regions of association with GD. As GD shares several susceptibility loci with other endocrin...

Autoimmune diseases (AIDs) have been shown to share a series of genetic susceptibility loci, including the HLA class II region, CTLA-4 and PTPN22, indicating the sharing of key pathways between diseases. Recently, the rs1801274 single nucleotide polymorphism (SNP) within the Fc gamma receptor 2a gene (FcGR2a) has been shown to be associated with several common AIDs including type 1 diabetes, rheumatoid arthritis and coeliac disease. FcGR2a is an immune mod...

PTPN22, encodes lymphoid tyrosine phosphatise (LYP), an important inhibitor of T lymphocyte activation and has been associated with numerous autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and Graves’ disease (GD). Consistent association has been reported between disease and a non-synonymous SNP +1858 C>T (rs2476601) encoding an Arginine to Tryptophan substitution at amino acid 620 of LYP. Our group was the first to show strong evidence of ...

In addition to the HLA gene region, two further genes involved in the inhibition of T cell signalling, CTLA-4 and PTPN22, have been consistently associated with autoimmune disease (AID), highlighting the important role played by molecules in this pathway in AID susceptibility. The Programmed Cell Death 1 gene (PDCD1) on chromosome 2q37.3 encodes PD-1 which is involved in providing a negative signal to activated T cells. Large case-control studies have show...

Protein tyrosine phosphatases (PTPs) such as PTPN22, that encodes lymphoid tyrosine phosphatase (LYP), are important regulators of cell signalling. LYP, through interaction with various accessory molecules including Grb2 and Csk kinase, has been shown to be particularly important in regulating signal transduction from the T cell receptor. The identification of PTPN22 as a susceptibility locus for Graves’ disease (GD) led us to hypothesise that other PTPs may...

Introduction: Monosomy 18q represents a partial deletion of the long arm of chromosome 18, with an estimated prevalence of 1:100 000. This syndrome is characterized by a highly variable phenotype. The symptoms and their severity depend on which part of the chromosome is missing. Most common manifestations are hypotonia, developmental delay, short stature, growth hormone deficiency, hearing loss and external ear anomalies, intellectual disability, palatal defects, dysmorphic fa...

Graves’ disease (GD) and Hashimotos’ thyroiditis (HT), two of the most common autoimmune thyroid diseases (AITD), are caused by both shared and disease specific genetic determinants. In females one copy of the X chromosome is randomly inactivated, and although inactivation should occur with a parent of origin ratio of 50:50, skewed X chromosome inactivation (XCI) can occur, whereby >80% of a specific copy of the X chromosome is inactivated. Increased skewed XCI i...

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...