Endocrine Abstracts

Background: Primary adrenal insufficiency (PAI) is most commonly congenital in children. PAI is genetically heterogeneous with some gene defects causing syndromic disease. A third of patients have no genetic diagnosis rendering their prognosis uncertain. We investigated families with a novel combination of PAI and steroid resistant nephrotic syndrome.Objective and hypotheses: To discover the genetic defect underlying this syndrome....

Chronically elevated glucocorticoid (GC) level impairs cognition. In rodents, elevated plasma GC levels, prior to an inflammatory challenge, potentiates neuroinflammation that is abolished by GR but not MR antagonism. 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1) increases intracellular GC levels by regenerating active GCs from inert forms. Inhibition/deficiency of 11β-HSD1 is protective against age-related cognitive decline presumably by lifelong reduced b...

Background: Hypothalamic KNDy neurons have recently been identified as key regulators of reproductive function by releasing three neuropeptides namely kisspeptin, neurokinin B (NKB) and dynorphin. Animal studies show they interact to control pulsatile GnRH release, which is vital for fertility. In animals, kisspeptin stimulates, NKB modulates and the opioid dynorphin inhibits GnRH pulsatility. However, the interaction of these peptides has never been studied in humans. To inve...

Introduction: Dysregulation of glucocorticoid (GC) metabolism is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The only available treatment for NAFLD is weight loss and the gold standard diagnostic test is liver biopsy, which is invasive and resource intensive. NAFLD ranges from simple steatosis, to inflammation (steatohepatitis/NASH), fibrosis and cirrhosis. It may be regarded as the hepatic manifestation of the metabolic syndrome and is strongl...

Introduction: Insulinomatosis is a rare disorder characterised by persistent hyperinsulinaemic hypoglycaemia (PHH) due to the occurrence of multifocal pancreatic insulinomas. This condition, whose pathogenesis is unknown, can occur in a familial setting. Paradoxically, while some family members develop PHH, others develop diabetes mellitus.Methods: We have identified a family with autosomal dominant familial insulinomatosis and diabetes. Exome sequencing...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by occurrence of parathyroid tumours and neuroendocrine tumours (NETs) of the pancreas and pituitary, which is caused by mutations of the MEN1 gene, encoding menin. Mouse models are important in elucidating mechanisms of MEN1 tumourigenesis and treatments, but the current models have limitations. Thus, in conventional heterozygous MEN1 knockout models, tumour d...