Endocrine Abstracts

This review was published in Nature Reviews Endocrinology. It covers recent advances in treatment of pituitary tumours secreting prolactin including long-term adverse effects of dopamine agonist therapy, outcomes following dopamine agonists withdrawal, advances in surgical tumour resection. In addition, there are sections on management during pregnancy, effects of hyperprolactinemia on bone and fracture risk, the management of cystic and aggressive prolactinomas. Prolactinomas...

Background: CYP11A1 encodes the P450 side chain cleavage enzyme (P450scc) responsible for initiating steroidogenesis and classically gives rise to disordered sex development plus adrenal and gonadal insufficiency. The rs6161 variant in exon 5 of CYP11A1 (c.940G>A; p.E314K) has previously been considered as ‘benign’. When next generation sequencing was performed in patients with primary adrenal insufficiency of unknown etiology the rs6161 variant was foun...

Background: CYP11A1 encodes the P450 side chain cleavage enzyme (P450scc) responsible for initiating steroidogenesis and classically gives rise to disordered sex development plus adrenal and gonadal insufficiency. The rs6161 variant in exon 5 of CYP11A1 (c.940G>A; p.E314K) has previously been considered as ‘benign’. When next generation sequencing was performed in patients with primary adrenal insufficiency of unknown etiology the rs6161 variant was foun...

Congenital imprinting disorders (IDs) are a group of rare conditions affecting growth, metabolism and development caused by aberrant expression of imprinted genes in a parent-of-origin dependent manner. The internationally recognised IDs are Prader Willi Syndrome (PWS), Angelman Syndrome (AS), Beckwith Wiedemann Syndrome (BWS), Silver Russell Syndrome (SRS), Temple Syndrome (TS14), Pseudohypoparathyroidism (PHP), Transient Neonatal Diabetes Mellitus (TNDM) and Kagami-Ogata Syn...

Background: The CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) genes are found in close proximity on human chromosome 8 and are highly polymorphic, enabling the definition of two common haplotypes. Haplotype1 includes the -344T and the Intron2 conversion polymorphisms in CYP11B2 and also the -1889T, -1859G polymorphisms in the regulatory region of CYP11B1. We and others have shown that these associate with increased aldosterone pr...

Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are highly homologous in their coding regions (95%), lie in tandem approximately 40kb apart in human chromosome 8, and may have arisen from gene duplication. The pattern of linkage disequilibrium (LD) of this region in a population is determined not only by the distribution of recombination events but also by demographic factors determining the amount of random genetic drift. There is suggestiv...

The corticosteroids aldosterone and cortisol are implicated in the aetiology of hypertension. The CYP11B1 and CYP11B2 genes encode 11β-hydroxlylase and aldosterone synthase; polymorphisms across the CYP11B1/B2 locus are associated with increased aldosterone production, inefficient 11β-hydroxlation and hypertension. While polymorphisms located in the promoter region of both genes may alter transcription factor binding, other variants located in th...

Aim: We propose that the circulating immune system and adipocyte size plays a role in the development of obesity related co-morbidities independent of body mass index (BMI).Methods: Clinical data and blood samples were collected from patients with severe obesity attending a hospital weight-management clinic and lean healthy controls. Patients were classified into metabolically ‘healthy obese’ or ‘unhealthy obese’ groups, based upon st...

A common NOS3 polymorphism (the gene which encodes endothelial nitric oxide synthase), a variable number of tandem repeats within Intron 4 has been associated with cardiovascular disorders in which nitric oxide bioactivity is impaired including myocardial infraction. Consistent characteristic changes in the pressure pulse wave shape have been associated with ageing, risk factors for cardiovascular disease and impaired NO bioactivity. Therefore pulse waveform analysis can be ut...

The major glucocorticoids (cortisol in man and corticosterone in the rat) play an important role in obesity and its attendant hypertension. However, there is no consistent evidence of glucocorticoid excess in simple obesity, suggesting that its role in the regulation of adipose tissue mass results from a more complex mechanism than adrenal hypersecretion of glucocorticoid. Glucocorticoid biosynthesis is not limited to the adrenal cortex; mRNA and enzymatic activity of 11β...