Endocrine Abstracts

Introduction: Heterozygote loss-of-function mutations in AIP (Aryl hydrocarbon receptor interacting protein) predispose to young-onset pituitary adenomas. Homozygote murine knockout model of AIP leads to lethality. While the majority of the 75 published AIP mutations result in truncated or missing proteins, missense mutations are more difficult to characterise and to establish their pathogenic role. We have identified the orthologue of AIP, CG1847, in Drosophila melanogaster. ...

Excess adiposity, especially in visceral depots, is a major driver of insulin resistance, fatty liver and hyperglycaemia in type 2 diabetes mellitus (T2DM). Treatment guidelines for T2DM emphasise lifestyle measures (principally diet and exercise) with pharmacotherapy as additionally required to achieve glycaemic control. Therapeutic strategies ideally assist weight control, avoid hypoglycaemia and address cardiovascular, renal and other risks. Metformin (weight neutral), whic...

Background: Fibrodysplasia ossificans progressiva (FOP) is a rare, genetic and devastating disease characterized by progressive heterotopic ossifications (HO) in muscles, tendons, ligaments and fascia. The formation of HO leads to severe contractures and early death. There are no approved medications yet. The STOPFOP team identified AZD0530 (saracatinib) as a potent, low nanomolar inhibitor of the mutant ALK2 kinase which is the unique genetic driver of this rare bone disease....

Introduction: Phaeochromocytomas are mostly benign tumours with origin from chromaffin tissue of adrenal glands, whereas paragangliomas aretumours located along the sympathetic or/and the parasympathetic chain. Generally they are quite rare neoplasms with ability of producing, storing and secreting of catecholamines. Predominatingly they are sporadic, but in some cases they may develop in progress of particular genetic syndromes, such as multiple endocrine neoplasia type 2 (ME...

CYP11B2 is a key enzyme of primary aldosteronism, and several factors are involved in the regulation of CYP11B2 expression and the overproduction of aldosterone. Somatic mutations in aldosterone-driver genes are strongly associated with CYP11B2 expression and have been only detected in the CYP11B2-positive tumor area, indicating that aldosterone producing adenoma (APA) intratumoral heterogeneity corresponds to non-uniform CYP11B2 expression in neoplastic cells. In addition, CY...

Metastatic thyroid cancer that are radioactive iodine-refractory (RAIR) have a high mortality, particularly if positive on [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET). We now have a better understanding of the genetic alterations implicated in the disease. Several studies along the last years have shown that constitutive activation of the mitogen-activated protein kinase (MAPK), triggered by rearrangements of RET and NTRK1 and activating mutations of RAS...

Introduction: Loss-of-function mutations in AIP are associated with familial isolated pituitary adenoma, often leading to gigantism due to invasive GH-secreting pituitary adenomas. One challenging problem in the management of patients carrying a missense AIP variant is to determine whether the missense variant is a disease-causing mutation or not. As most of the molecular mechanisms involved in the control of growth and the cell cycle are well-conserved, we p...

Introduction: Mutations affecting hypothalamic development in humans have been identified in genes that affect isolated domains of hypothalamic function leading to restricted phenotypes, such as obesity or hypogonadotrophic hypogonadism. We describe the first human cases of diabetes insipidus and combined pituitary hormone deficiency due to a mutation in a gene regulating hypothalamic development.Results: Six affected individuals from a highly consanguin...

Audit data were prospectively collected on establishing a multidisciplinary children’s diabetes service in a small district general hospital serving a mixed urban and rural community in 1989. Only two team members DSN and paediatrician were unchanged until 2009.The number of children diagnosed with diabetes more than doubled, with overall incidence rates of ~27/100 000. From 1998 until 2008 all newly diagnosed children were managed as outpatients un...

I live in Umbria and have recently become concerned for the young couple, Amanda Knox and Raffaele Sollecito, convicted of the horrific murder in Perugia on November 1st 2007 of English student Meredith Kercher, They were supposedly acting with an Ivorian, Rudy Guede, who was tried and convicted separately.I am still haunted by a wrongful conviction half a lifetime ago, which involved the murder of 11-year old Lesley Susan Molseed. Just before Christmas ...