Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Abstract

Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-18 dihydroxyphenylalanine-positron emission tomography. Newer and improved isotopes are currently in development to provide increased diagnostic accuracy in identifying lesions and performing successful surgical resection with the ultimate aim of curing the condition. Rapid diagnostics and innovative methods of management, including a wider range of treatment options, have resulted in a reduction in co-morbidities associated with HH with improved quality of life and long-term outcomes. Potential future developments in the management of this condition as well as pathways to transition of the care of these highly vulnerable children into adulthood will also be discussed.

Clinical characteristics, outcome, and predictors of neurological sequelae of persistent congenital hyperinsulinism: A single tertiary center experience

“…Up until recently, mutations in 16 variable genes have been identified including ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1, PMM2, CACNA1D, FOXA2, EIF2S3 and TRMT10A genes. Mutations in ABCC8 and KCNJ11 genes represent the most common ones, which encode sulfonyl urea receptor 1 (SUR1) and the potassium inward rectifier 6.2 (Kir6.2) subunits of the K‐ATP channel, respectively 3 …”

“…The first line medical treatment is the K‐ATP channel opener; oral diazoxide and the second line is octreotide injections 6 . Nifedipine was found to be a successful therapy for CHI in some case reports but it is generally recommended to use it as an add‐on therapy with diazoxide or octreotide, or after pancreatectomy, but occasionally as a monotherapy 3 . Sirolimus use has shown variable results with potential serious side effects 7 .…”

Diagnosis of congenital Hyperinsulinism can occur not only in infancy but also in later age: a new flow chart from a single center experience

“…As affirmed by others, 18 F-DOPA PET-CT should be performed when a focal form is suspected in the presence of Dx-unresponsiveness (although some rare focal forms respond to diazoxide) and if no mutation is detected at all; in these patients images provided by 18 F-DOPA PET-CT can address the choice of surgical treatment [8,9,27,29]. Thus, in late presentation cases, we can assume that 18 F-DOPA PET-CT should be performed only to exclude insulinoma, since it can occur at any age, but is very rare in pediatric age, and could represent a manifestation of Multiple endocrine neoplasia type 1 (MEN1) [30][31][32]. Insulinoma could either be detected by 18 F-DOPA PET-CT or (68) Ga-DOTATATE [32].…”

The use of long-acting somatostatin analogs in congenital hyperinsulinism

“…На сегодняшний день опыт применения аналогов соматостатина длительного действия в лечении ВГИ ограничен единичными случаями и небольшими группами пациентов [9][10][11]. Также существует проблема отсутствия единой схемы терапии ланреотидом, в клинической практике отмечается потребность в калькуляторе расчета эффективной дозы препарата [12].…”