Endocrine Abstracts

Phaeochromocytomas are life-threatening catecholamine-producing tumours of the adrenal medulla. Our understanding of their pathogenesis is incomplete, with limited ability to predict malignant potential and disappointing treatment results in disseminated disease. Phaeochromocytomas occur in the inherited cancer syndrome von Hippel-Lindau (VHL). One function of VHL protein is in the formation and maintenance of primary cilia. These are microtubule-based organelles that protrude...

Introduction: Primary, non-motile, cilia are microtubule-based organelles that protrude from the cell membrane into the extracellular environment of virtually all nucleated mammalian cells. They function as signalling platforms involved in the transduction of extracellular stimuli and have an important role in cell cycle regulation. Disruption of primary cilia structure and therefore function has been identified in a range of cancers including kidney, breast, pancreatic and pr...

Mutations in each of the 4 subunits of succinate dehydrogenase (SDH) – SDHA, B, C and D predispose to development of phaeochromocytomas and paragangliomas. Loss of SDH function leads to accumulation of succinate which acts as an oncometabolite to drive tumourigenesis. However, mutations in SDHB have an increased likelihood of causing metastatic disease, compared to mutations in the other SDH subunits. The reasons behind this increased risk remai...

Background: Childhood growth is an indicator of health/well-being. Growth monitoring identifies treatable conditions in apparently healthy children and prevents inappropriate referrals. Systematic growth monitoring is not currently a UK priority and growth disorders are frequently diagnosed late.Objective: Develop and test the accuracy of GrowthMonitor, an app which enables families to measure a child’s height at home as a cost-effective alternative...

MC2R is the smallest member of the GPCR superfamily and belongs to the melanocortin subfamily of receptors. The pituitary hormone ACTH acts through MC2R to induce the intracellular production cAMP and the stimulation of steroidogenesis. We have previously shown that MC2R interacts with a single-transmembrane domain protein called MRAP (melanocortin-2 receptor accessory protein) and is required for the functional expression of MC2R. Both MC2R and MRAP are mutated in the rare re...

Loss of function of succinate dehydrogenase (SDH), caused by mutations in each of the 4 subunits – SDHA/B/C and D – is associated with development of phaeochromocytomas and paragangliomas (PPGLs). The mutations lead to loss of enzymatic activity and subsequent accumulation of the oncometabolite succinate, a driver of tumourigenesis. It is well established but poorly understood why mutations in SDHB are associated with more aggressi...

Background: Growth monitoring identifies treatable conditions in apparently healthy children and prevents inappropriate referrals. Systematic growth monitoring is not currently a UK priority and growth disorders are frequently diagnosed late.Objectives: Develop and test the accuracy of a smartphone app which enables families to measure a child’s height at home as a cost-effective alternative to primary care growth monitoring.M...

Background: 20% of the familial isolated pituitary adenoma (FIPA) population harbour an aryl hydrocarbon receptor-interacting protein (AIP) gene mutation. The recognition of whether a variant is pathogenic can be difficult, in cases where the observed change does not lead to a truncated protein. Segregation with disease in a family, in silico predictions, loss of heterozigosity in the tumour, in vitro functional studies and screening of the variant in controls may help in asce...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease due in ∼25% of cases to defects in the ACTH receptor (melcanocortin 2 receptor -MC2R). Slow progress in characterization of these mutations has been made in view of the difficulty in establishing a functional heterologous cell transfection system for the MC2R, and the best available models relate to the mouse Y6/OS3 cell lines. However we have shown previously that the melanocortin 2 receptor ...

Mutations in AIP have been identified in a significant proportion of families with pituitary adenomas, most commonly in familial acromegaly. However, no data are available about the pituitary expression of AIP and how lack of AIP is involved in tumorigenesis.We identified 10 kindreds with AIP mutations out of 31 families. We studied RNA and protein expression of AIP in normal as well as familial and sporadic pituitary adenomas. In the normal pituitary st...