Endocrine Abstracts

Background: Congenital hyperinsulinism (CHI) is a clinically heterogeneous condition. Mutations in seven genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1 and HNF4A) are known to cause CHI.Aim: To characterise the clinical and molecular aspects of a large cohort of patients with CHI.Methodology: 300 patients with biochemically confirmed CHI were recruited. Detailed clinical information was collected prior to geno...

Introduction: Hyperinsulinaemic hypoglycaemia (HH), characterized by unregulated insulin secretion from pancreatic β-cells, is an important cause of hypoglycaemia in children. Mutations in the KATP channel genes (ABCC8/KCNJ11) are the most common cause of congenital HH. The second common cause, hyperinsulinism hyperammonaemia (HIHA) syndrome caused by mutations in GLUD1 gene, is associated with elevated serum ammonia and protein sensitivity. W...

Locus-specific databases (LSDBs) have been recently developed in response to the increasing number of genetic changes reported in the human genome. LSDBs have been created for several genes implicated in endocrine syndromes, for example MEN1, VHL, RET, GNAS, PRKAR1A and the SDH subunits. Mutations in AIP are found in about 20% of familial isolated pituitary adenoma (FIPA) patients.The aim of this proj...

Congenital hyperinsulinism (CHI) is a cause of severe and persistent hypoglycaemia due to unregulated insulin secretion from pancreatic β-cells. Mutations in the ABCC8 and KCNJ11 genes are the most common cause of medically unresponsive CHI. Histologically there are three major subgroups, focal, diffuse and atypical. The pathophysiology of focal CHI is complex and involves a two hit process with the patient firstly inheriting a paternal ABCC8/KCNJ11 m...

Background: Galactokinase catalyses the first committed step in galactose metabolism, the conversion of galactose to galactose-1-phosphate. Galactokinase deficiency is an extremely rare form of galactosaemia and the most frequent complication reported is cataracts. Congenital hyperinsulinism (CHI) is a cause of severe hypoglycaemia in the newborn period.Aims: To report the diagnostic pitfalls with bedside blood glucose testing in a neonate with combined ...

Background: The pancreatic β-cell KATP channel plays a key role in glucose stimulated insulin secretion and is encoded by the genes ABCC8 and KCNJ11. Recessive mutations in ABCC8/KCNJ11 cause severe medically unresponsive HH. Recently, dominant mutations in these genes have been described that cause mild, medically responsive HH. Controversy exists on whether these dominant ABCC8/KCNJ11 mutations predispose to diabetes mellitus in ad...

Introduction: Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of severe and persistent hypoglycaemia in neonates. The treatment of diazoxide unresponsive HH involves pancreatectomy. Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cellular proliferation. We aimed to evaluate the efficacy of mTOR inhibitor Sirolimus and assess mTOR expression in the pancreas of infants with severe HH.Methods: Four infants with severe, ...

Mutations in the co-chaperone molecule AIP account for a predisposition to pituitary tumours in some families with familial isolated pituitary adenomas (FIPA). We now report on four apparently-unrelated families with the same mutation and originating from the same geographical area, suggesting a possible founder mutation.The index patient had gigantism (19 years, 208 cm) and had a female 4th cousin, once removed (13 years, 191 cm) with a large pituitary ...

Introduction: Approximately 25% of medullary thyroid cancer (MTC) cases arise in a familial setting, either as MEN2 or fMTC. While most of these are caused by mutations in the RET gene, a few families have unidentified mutations. Recently, a frameshift mutation in the ESR2 gene (coding oestrogen receptor beta) was found in a family with RET-negative fMTC associated with C-cell hyperplasia. In vitro, transfection of mutant ESR2 led t...

The islet-enriched transcription factor MAFA regulates the expression of genes critical to beta cell function and insulin secretion. We previously described anovel MAFA mutation (c.191C > T, p.S64F) causing familial insulinomatosis and diabetes mellitus, with male carriers more often developing diabetes and females more prone to insulinomatosis. The exact molecular mechanisms underlying these phenotypes are unclear. In this study, we assessed glucose metabolism an...