Endocrine Abstracts

Recently, rare loss-of-function mutations of melanocortin-2-receptor accessory protein 2 (MRAP2) have been associated with severe, early-onset obesity in humans. In addition, whole body deletion and targeted brain specific deletion of the Mrap2 gene resulted in severe obesity in mice. In vitro data have shown Mrap2 interaction with the melanocortin-4-receptor (MC4R) affecting receptor signalling as a consequence. However, the mechanism by which Mrap2...

The overproduction of ACTH, in conditions such as Congenital Adrenal Hyperplasia (CAH) leads to significant morbidity. Current treatment with glucocorticoids does not adequately suppress plasma ACTH, resulting in excess adrenal androgen production. At present, there is no effective medical treatment that would directly block ACTH action. Such a therapy, especially one that can be orally administered, would be of great clinical value allowing a ‘block and replace’ tre...

PBF is a ubiquitous glycoprotein which is over-expressed particularly in endocrine and endocrine-related cancers. Previously classified as a proto-oncogene, 11 substitution-missense mutations of PBF have now been reported in tumours from patients with ovarian, prostate and colorectal cancers via the COSMIC database, suggesting PBF may in fact be an oncogene. We have therefore examined the biological implications of all 11 mutations. Substitution mutations, which occurred acros...

Whilst, radioiodine ablation is an effective therapy for many patients with thyroid cancer, a subset of patients are incapable of accumulating sufficient iodide-131 for effective treatment, due to low sodium–iodide symporter (NIS) activity. Previous work has identified that the overexpression of pituitary tumor transforming gene (PTTG) binding factor (PBF) in thyroid cells leads to the redistribution of NIS from the plasma membrane into intracellular vesicles, thereby red...

Congenital hyperinsulinaemic hypoglycaemia is generally characterised by low levels of ketone bodies, fatty acids and branched chain amino acids at the time of severe hypoglycaemia, and by a requirement for a relatively high rate of glucose infusion (>10 mg/kg per min) to maintain euglycaemia. It is caused by physiologically inappropriate insulin secretion from the pancreatic beta cells due to mutations that uncouple insulin secretion from normal hyperglycaemic and other s...

Dysregulation of the enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistant states, however longitudinal changes in glucocorticoid metabolism over time have not been investigated. This study was designed to evaluate the role of pre-receptor glucocorticoid metabolism in the development of insulin resistance and obesity. 24 h urinary glucocorticoid and mineralocorticoid metabolites were measured by gas chroma...

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess. Hyperandrogenism may correlate with metabolic risk but PCOS consensus criteria currently define androgen excess on the basis of serum testosterone only. Here we studied the utility of the androgen precursor serum androstenedione in conjunction with serum testosterone as a predictor of metabolic dysfunction in PCOS.86 PCOS patients fulfilling Rott...

Thyroid growth and differentiation are regulated by TSH via its receptor (TSHR), whilst growth factors signal in parallel via the MAPK/ERK and PI3K/AKT pathways. Aberrant thyroid growth is largely driven by molecular alterations within these signalling pathways. The proto-oncogene pituitary tumor-transforming gene-binding factor (PBF) is expressed in normal thyroid and upregulated in human goitre and thyroid cancer. High PBF expression is associated with tumour recurrence, dis...

The causative link between circulating glucocorticoid excess and osteoporosis is established. Although circulating cortisol levels do not change significantly with age, local tissue metabolism may be implicated in age-related bone loss. The enzyme11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) increases local cortisol production, is expressed in human osteoblasts and its activity increases with age leading to a decrease in bone formation. We hypothesised that sele...

A 48-year-old man was referred for investigation of uncontrolled hypertension on four agents (olmesartan, felodipine, hydrochlorothiazide and spironolactone) and a 3 cm right-sided adrenal adenoma (pre-contrast Hounsfield units 25). Endocrine investigation for the hypertension and adrenal mass included: androstenedione 19.9 nmol/l 2.8–10.5) (elevated on two occasions on a Siemens Coat-A-Count assay), DHEA 0.7 μmol/l (2.1–15.2), 1 mg overnight dexamethasone suppr...