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  • Review Article
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Advances in the diagnosis and management of hyperinsulinemic hypoglycemia

Nature Clinical Practice Endocrinology & Metabolism volume 5, pages 101–112 (2009)Cite this article

An Erratum to this article was published on 01 March 2009

Abstract

Hyperinsulinemic hypoglycemia (HH) is a consequence of unregulated insulin secretion by pancreatic β-cells and is a major cause of hypoglycemic brain injury and mental retardation. Congenital HH is caused by mutations in genes involved in regulation of insulin secretion, seven of which have been identified (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1 and HNF4A). Severe forms of congenital HH are caused by mutations in ABCC8 and KCNJ11, which encode the two components of the pancreatic β-cell ATP-sensitive potassium channel. Mutations in HNF4A, GLUD1, CGK, and HADH lead to transient or persistent HH, whereas mutations in SLC16A1 cause exercise-induced HH. Rapid genetic analysis combined with an understanding of the histological features (focal or diffuse disease) of congenital HH and the introduction of 18F-L-3,4-dihydroxyphenylalanine PET-CT to guide laparoscopic surgery have totally transformed the clinical approach to this complex disease. Adult-onset HH is mostly caused by an insulinoma; however, it has also been reported to present as postprandial HH in patients with noninsulinoma pancreatogenous hypoglycemia syndrome, in those who have undergone gastric-bypass surgery for morbid obesity, and in those with mutations in the insulin-receptor gene.

Key Points

  • Hyperinsulinemic hypoglycemia is a consequence of unregulated insulin secretion by pancreatic β-cells and is a major cause of brain injury and mental retardation in children

  • Congenital hyperinsulinemic hypoglycemia is caused by mutations in key genes that are involved in the regulation of insulin secretion, seven of which have been so far identified: ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1 and HNF4A

  • Rapid genetic screening for mutations in ABCC8 and KCNJ11 combined with recent advances in 18F-L-DOPA-PET–CT imaging and laparoscopic surgery have transformed the management of children with focal congenital hyperinsulinemic hypoglycemia

  • 18F-L-DOPA-PET–CT scans enable accurate preoperative localization of pancreatic focal lesions focus and hence offer the prospect of cure by partial pancreatectomy

  • An insulinoma accounts for the majority of the cases of adult-onset hyperinsulinemic hypoglycemia and, in 99% of cases, is detectable by a prolonged fast

  • Postprandial hyperinsulinemic hypoglycemia in adults can be cause by noninsulinoma pancreatogenous hypoglycemia syndrome, gastric bypass surgery for morbid obesity, or mutations in the insulin receptor gene

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Figure 1: Outline of the molecular mechanisms that regulate insulin secretion in pancreatic β-cells.
Figure 2: Summary of the molecular mechanisms that lead to congenital hyperinsulinemic hypoglycemia.
Figure 3: Outline of a diagnostic and management algorithm for patients with congenital hyperinsulinemic hypoglycemia.
Figure 4: An 18F-L-DOPA-PET scan of a focal lesion in the tail of the pancreas.

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  1. RR Kapoor is a Clinical Research Fellow and Honorary Specialist Registrar, C James is a Postdoctoral Researcher, and K Hussain is a Consultant Pediatric Endocrinologist and Honorary Senior Lecturer, all at the Institute of Child Health, University College London and Great Ormond Street Hospital for Children National Health Services Trust, London, UK.,

    Ritika R Kapoor, Chela James & Khalid Hussain

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Kapoor, R., James, C. & Hussain, K. Advances in the diagnosis and management of hyperinsulinemic hypoglycemia. Nat Rev Endocrinol 5, 101–112 (2009). https://doi.org/10.1038/ncpendmet1046

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