Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017:2017:9.
doi: 10.1186/s13633-017-0048-8. Epub 2017 Aug 29.

Diagnosis and treatment of hyperinsulinaemic hypoglycaemia and its implications for paediatric endocrinology

Huseyin Demirbilek  1 , Sofia A Rahman  2 , Gonul Gulal Buyukyilmaz  1 , Khalid Hussain  3
Affiliations
Review

Diagnosis and treatment of hyperinsulinaemic hypoglycaemia and its implications for paediatric endocrinology

Huseyin Demirbilek et al. Int J Pediatr Endocrinol. 2017.

Abstract

Glucose homeostasis requires appropriate and synchronous coordination of metabolic events and hormonal activities to keep plasma glucose concentrations in a narrow range of 3.5-5.5 mmol/L. Insulin, the only glucose lowering hormone secreted from pancreatic β-cells, plays the key role in glucose homeostasis. Insulin release from pancreatic β-cells is mainly regulated by intracellular ATP-generating metabolic pathways. Hyperinsulinaemic hypoglycaemia (HH), the most common cause of severe and persistent hypoglycaemia in neonates and children, is the inappropriate secretion of insulin which occurs despite low plasma glucose levels leading to severe and persistent hypoketotic hypoglycaemia. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) constitute the underlying molecular mechanisms of congenital HH. Since insulin supressess ketogenesis, the alternative energy source to the brain, a prompt diagnosis and immediate management of HH is essential to avoid irreversible hypoglycaemic brain damage in children. Advances in molecular genetics, imaging methods (18F-DOPA PET-CT), medical therapy and surgical approach (laparoscopic and open pancreatectomy) have changed the management and improved the outcome of patients with HH. This up to date review article provides a background to the diagnosis, molecular genetics, recent advances and therapeutic options in the field of HH in children.

Keywords: Children; Congenital hyperinsulinaemia; Diffuse; Focal; Hyperinsulinaemic hypoglycaemia; Sirolimus.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Regulation of insulin release from pancreas β-cell and site of gene mutations involve in the genetics etiology of HH (SUR1: Sulphonyurea receptor 1; Kir 6.2: Inward rectifier potassium channel 6.2; K: Potassium; MCT1: Monocarboxlase transferase-1; Glu: glucose; P: Phosphorus; PGM1: Phosphoglucomutase 1; PMM2: Phosphomannose-mutase 2; UCP2: Mitochondrial uncoupling protein 2; NH3: Ammonia; GDH: Glutamate dehydrogenase; GLUD1: Glutamate dehydrogenase 1 gene; HADH: Hydroxy-acyl-CoA dehydrogenase; HNF1A and 4A: Hepatocyte nuclear factor 1 and 4; Ca+2: Calcium
Fig. 2
Fig. 2
18F–DOPA-PET/CT scan images of focal CHI (a and c), histological figure of diffuse (b) and focal (d) disease and normal pancreas islet cell (e). SUV 5.3 and SUV 5.7 indicate focal uptake of 18F–DOPA, red arrows show large nuclei of β-cell in diffuse disease
Fig. 3
Fig. 3
A schematic appearance of pancreatectomy methods for surgery of congenital HH. While for a focal case only limited lesionectomy (a and b) provide cure without any postsurgical complication, in case of diffuse disease, extensive excision (laparoscopic or open) of a certain part of pancreas may result in continuum of the HH or developing exocrine and endocrine pancreas insufficiency
Fig. 4
Fig. 4
An algorithm for the management of patients with congenital HH
See this image and copyright information in PMC

References

    1. Shah P, Rahman SA, Demirbilek H, Güemes M, Hussain K. Hyperinsulinaemic hypoglycaemia in children and adults. Lancet Diabetes Endocrinol 2016. doi: 10.1016/S2213-8587(16)30323-0. - PubMed
    1. Hussain K, Aynsley-Green A. Hyperinsulinism in infancy: understanding the pathophysiology. Int J Biochem Cell Biol. 2003;35:1312–1317. doi: 10.1016/S1357-2725(03)00103-1. - DOI - PubMed
    1. Meissner T, Wendel U, Burgard P, Schaetzle S, Mayatepek E. Long-term follow-up of 114 patients with congenital hyperinsulinism. Eur J Endocrinol. 2003;149(1):43–51. - PubMed
    1. Arya VB, Flanagan SE, Kumaran A, Shield JP, Ellard S, Hussain K, Kapoor RR. Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age. Arch Dis Child Fetal Neonatal Ed. 2013;98:F356–F358. doi: 10.1136/archdischild-2012-302880. - DOI - PMC - PubMed
    1. Kapoor RR, Flanagan SE, Arya VB, Shield JP, Ellard S, Hussain K. Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism. Eur J Endocrinol. 2013;168:557–564. doi: 10.1530/EJE-12-0673. - DOI - PMC - PubMed