Congenital Hyperinsulinism: Diagnosis and Treatment Update

Abstract

Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate secretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms leading to congenital HH. In HH due to the inhibitory effect of insulin on lipolysis and ketogenesis there is suppressed ketone body formation in the presence of hypoglycaemia thus leading to increased risk of hypoglycaemic brain injury. Therefore, a prompt diagnosis and immediate management of HH is essential to avoid hypoglycaemic brain injury and long-term neurological complications in children. Advances in molecular genetics, imaging techniques (18F-DOPA positron emission tomography/computed tomography scanning), medical therapy and surgical advances (laparoscopic and open pancreatectomy) have changed the management and improved the outcome of patients with HH. This review article provides an overview to the background, clinical presentation, diagnosis, molecular genetics and therapy in children with different forms of HH.

Somatostatin Analogs in Clinical Practice: A Review

“…Octreotide LAR and lanreotide ATG have been used successfully in children with CHI, even in early infancy. Using long-acting formulations increases treatment adherence and improves quality of life (QoL) [133].…”

Hypoglycemia After Gastric Bypass Surgery: Current Concepts and Controversies

“…Although gastrointestinal side-effects of gas and abdominal cramping can limit tolerance, introduction of low doses (e.g., 25 mg before each meal) and slow escalation to the maximal tolerated dose can be effective in limiting side-effects. Diazoxide, which reduces insulin secretion by inhibition of b-cell ATP-sensitive potassiu channels, has been used in persistent hyperinsulinemic hypoglycemia of infancy, insulinoma, and noninsulinoma pancreatogenous hypoglycemia syndrome (52). Case reports in PBH show efficacy for doses of 50 mg twice daily (BID) (53) or 100 mg BID (54), but side-effects, including fluid retention, edema, nausea, hypotension, and headache, can limit patient adherence.…”

Hyperinsulinaemic hypoglycaemia: A rare association of vanishing white matter disease

“…None of the currently identified genes associated with hyperinsulinism encode proteins involved with adrenaline, noradrenaline or other counter-regulatory hormones, however, a genetic cause is not identified in around 40% of cases of hyperinsulinism. 37,38 To our knowledge, hyperinsulinism has not previously been reported in VWM. A second pathology seems unlikely in nonconsanguineous families where exome testing did not reveal a cause of hyperinsulinism, however a relationship between hyperinsulinism and VWM is neither confirmed nor readily explained with current knowledge of the pathophysiology.…”