title: Hyperinsulinaemic hypoglycaemia in children and adults.
abstract: Pancreatic β cells are functionally programmed to release insulin in response to changes in plasma glucose concentration. Insulin secretion is precisely regulated so that, under normal physiological conditions, fasting plasma glucose concentrations are kept within a narrow range of 3·5-5·5 mmol/L. In hyperinsulinaemic hypoglycaemia, insulin secretion becomes dysregulated (ie, uncoupled from glucose metabolism) so that insulin secretion persists in the presence of low plasma glucose concentrations. Hyperinsulinaemic hypoglycaemia is the most common cause of severe and persistent hypoglycaemia in neonates and children. At a molecular level, mutations in nine different genes can lead to the dysregulation of insulin secretion and cause this disorder. In adults, hyperinsulinaemic hypoglycaemia accounts for 0·5-5·0% of cases of hypoglycaemia and can be due either to β-cell tumours (insulinomas) or β-cell hyperplasia. Rapid diagnosis and prompt management of hyperinsulinaemic hypoglycaemia is essential to avoid hypoglycaemic brain injury, especially in the vulnerable neonatal and childhood periods. Advances in the field of hyperinsulinaemic hypoglycaemia include use of rapid molecular genetic testing for the disease, application of novel imaging techniques (6-[fluoride-18]fluoro-levodopa [18F-DOPA] PET-CT and glucagon-like peptide 1 (GLP-1) receptor imaging), and development of novel medical treatments (eg, long-acting octreotide formulations, mTOR inhibitors, and GLP-1 receptor antagonists) and surgical therapies (eg, laparoscopic surgery).
authors.affiliation: Genetics and Genomic Medicine Programme, University College London (UCL) Institute of Child Health, London, UK; Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Pratik
authors.initials: P
authors.lastname: Shah
authors.affiliation: Genetics and Genomic Medicine Programme, University College London (UCL) Institute of Child Health, London, UK.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Rahman
authors.affiliation: Department of Paediatric Endocrinology, Hacettepe University, Ankara, Turkey.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Demirbilek
authors.affiliation: Genetics and Genomic Medicine Programme, University College London (UCL) Institute of Child Health, London, UK; Endocrinology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Güemes
authors.affiliation: Department of Pediatric Medicine, Sidra Medical & Research Center, Outpatient Clinic, Doha, Qatar. Electronic address: khussain@sidra.org.
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D000293:Adolescent; D002648:Child; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D007003:Hypoglycemia / Q000175:diagnosis / Q000209:etiology / Q000628:therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D005947:Glucose