Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Reviews in Endocrine and Metabolic Disorders
Published in: Reviews in Endocrine and Metabolic Disorders 4/2020

Open Access 01-12-2020 | Insulins

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

Authors: Maria Gϋemes, Sofia Asim Rahman, Ritika R. Kapoor, Sarah Flanagan, Jayne A. L. Houghton, Shivani Misra, Nick Oliver, Mehul Tulsidas Dattani, Pratik Shah

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 4/2020

Login to get access

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.
Literature
1.
Ahrén B. Autonomic regulation of islet hormone secretion--implications for health and disease. Diabetologia. 2000;43(4):393–410.PubMed
2.
Senniappan S, Shanti B, James C, Hussain K. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. J Inherit Metab Dis. 2012;35(4):589–601.PubMed
3.
Chinoy, A. et al. ‘Focal congenital hyperinsulinism as a cause for sudden infant death’. Pediatr Dev Pathol. 2019;22(1):65–69.
4.
Guyot A, Moreau F, Eberhard M, Gaulier JM, Paraf F. Congenital hyperinsulinism revealed by sudden infant death. Ann Pathol. 2017;37(5):429–32.PubMed
5.
Avatapalle HB, et al. Abnormal neurodevelopmental outcomes are common in children with transient congenital Hyperinsulinism. Front Endocrinol (Lausanne). 2013;4:60.
6.
Güemes M, Rahman SA, Hussain K. What is a normal blood glucose? Arch Dis Child. 2016;101:569–574.
7.
Thornton PS, Stanley CA, de Leon DD, Harris D, Haymond MW, Hussain K, et al. Recommendations from the pediatric Endocrine Society for evaluation and Management of Persistent Hypoglycemia in neonates, infants, and children. J Pediatr. 2015;167(2):238–45.PubMed
8.
Hussain K. Diagnosis and management of hyperinsulinaemic hypoglycaemia of infancy. Horm Res. 2008;69(1):2–13.PubMed
9.
Patel P, Charles L, Corbin J, et al. A unique allosteric insulin receptor monoclonal antibody that prevents hypoglycemia in the SUR-1-/- mouse model of KATP hyperinsulinism. MAbs. 2018;10(5):796–802. 
10.
Arya VB, Mohammed Z, Blankenstein O, de Lonlay P, Hussain K. Hyperinsulinaemic hypoglycaemia. Horm Metab Res. 2014;46(3):157–70.
11.
Vannucci RC, Vannucci SJ. Hypoglycemic brain injury. Semin Neonatol. 2001;6(2):147–55.
12.
Hussain K, et al. An activating mutation of AKT2 and human hypoglycemia. Science. 2011;334(6055):474.
13.
Staufner C, Lindner M, Dionisi-Vici C, Freisinger P, Dobbelaere D, Douillard C, et al. Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options. J Inherit Metab Dis. 2016;39(2):273–83.
14.
Gillis D, Krishnamohan A, Yaacov B, Shaag A, Jackman JE, Elpeleg O. TRMT10A dysfunction is associated with abnormalities in glucose homeostasis, short stature and microcephaly. J Med Genet. 2014;51(9):581–6.
15.
Senniappan S, Arya VB, Hussain K. The molecular mechanisms, diagnosis and management of congenital hyperinsulinism. Indian J Endocrinol Metab. 2013;17(1):19–30.PubMedPubMedCentral
16.
Inagaki N, et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995;270(5239):1166–70.PubMed
17.
Kapoor RR, et al. Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism. Eur J Endocrinol. 2013;168(4):557–64.PubMedPubMedCentral
18.
Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, et al. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science. 1995;268(5209):426–9.PubMed
19.
Thomas P, Ye Y, Lightner E. Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy. Hum Mol Genet. 1996;5(11):1809–12.PubMed
20.
Taschenberger G, Mougey A, Shen S, Lester LB, LaFranchi S, Shyng SL. Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels. J Biol Chem. 2002;277(19):17139–46.PubMed
21.
Huopio H, et al. K(ATP) channels and insulin secretion disorders. Am J Physiol Endocrinol Metab. 2002;283(2):E207–16.PubMed
22.
Huopio H, Reimann F, Ashfield R, Komulainen J, Lenko HL, Rahier J, et al. Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1. J Clin Invest. 2000;106(7):897–906.PubMedPubMedCentral
23.
Huopio H, Otonkoski T, Vauhkonen I, Reimann F, Ashcroft FM, Laakso M. A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. Lancet. 2003;361(9354):301–7.PubMed
24.
Flanagan SE, Kapoor RR, Banerjee I, Hall C, Smith VV, Hussain K, et al. Dominantly acting ABCC8 mutations in patients with medically unresponsive hyperinsulinaemic hypoglycaemia. Clin Genet. 2011;79(6):582–7.PubMedPubMedCentral
25.
Pinney SE, MacMullen C, Becker S, Lin YW, Hanna C, Thornton P, et al. Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. J Clin Invest. 2008;118(8):2877–86.PubMedPubMedCentral
26.
Kapoor RR, et al. Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8/KCNJ11 mutations. Diabetologia. 2011;54(10):2575–83.PubMedPubMedCentral
27.
Stanley CA, et al. Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med. 1998;338(19):1352–7.PubMed
28.
Stanley CA, Fang J, Kutyna K, Hsu BY, Ming JE, Glaser B, et al. Molecular basis and characterization of the hyperinsulinism/hyperammonemia syndrome: predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene. HI/HA Contributing Investigators. Diabetes. 2000;49(4):667–73.PubMed
29.
Kapoor RR, Flanagan SE, Fulton P, Chakrapani A, Chadefaux B, Ben-Omran T, et al. Hyperinsulinism-hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations. Eur J Endocrinol. 2009;161(5):731–5.PubMedPubMedCentral
30.
Glaser B, et al. Familial hyperinsulinism caused by an activating glucokinase mutation. N Engl J Med. 1998;338(4):226–30.PubMed
31.
Christesen HB, et al. Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation. Eur J Endocrinol. 2008;159(1):27–34.PubMed
32.
Cuesta-Munoz AL, et al. Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. Diabetes. 2004;53(8):2164–8.PubMed
33.
Christesen HB, Jacobsen BB, Odili S, Buettger C, Cuesta-Munoz A, Hansen T, et al. The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy. Diabetes. 2002;51(4):1240–6.PubMed
34.
Heslegrave AJ, et al. Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of function mutations in 3-Hydroxyacyl-CoA dehydrogenase. Orphanet J Rare Dis. 2012;7:25.PubMedPubMedCentral
35.
Filling C, Keller B, Hirschberg D, Marschall HU, Jörnvall H, Bennett MJ, et al. Role of short-chain hydroxyacyl CoA dehydrogenases in SCHAD deficiency. Biochem Biophys Res Commun. 2008;368(1):6–11.PubMed
36.
Clayton PT, et al. Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest. 2001;108(3):457–65.PubMedPubMedCentral
37.
Molven A, Matre GE, Duran M, Wanders RJ, Rishaug U, Njølstad PR, et al. Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. Diabetes. 2004;53(1):221–7.PubMed
38.
Kapoor RR, James C, Flanagan SE, Ellard S, Eaton S, Hussain K. 3-Hydroxyacyl-coenzyme a dehydrogenase deficiency and hyperinsulinemic hypoglycemia: characterization of a novel mutation and severe dietary protein sensitivity. J Clin Endocrinol Metab. 2009;94(7):2221–5.PubMed
39.
Flanagan SE, et al. Genome-wide homozygosity analysis reveals HADH mutations as a common cause of diazoxide-responsive hyperinsulinemic-hypoglycemia in consanguineous pedigrees. J Clin Endocrinol Metab. 2011;96(3):E498–502.PubMedPubMedCentral
40.
Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan SE, Ellard S. Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1 alpha and 4 alpha in maturity-onset diabetes of the young and hyperinsulinemic hypoglycemia. Hum Mutat. 2013;34(5):669–85.PubMed
41.
Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 2007;4(4):e118.PubMedPubMedCentral
42.
Kapoor RR, Locke J, Colclough K, Wales J, Conn JJ, Hattersley AT, et al. Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations. Diabetes. 2008;57(6):1659–63.PubMed
43.
Flanagan SE, et al. Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations. Eur J Endocrinol. 2010;162(5):987–92.PubMedPubMedCentral
44.
McGlacken-Byrne SM, et al. The evolving course of HNF4A hyperinsulinaemic hypoglycaemia--a case series. Diabet Med. 2014;31(1):e1–5.PubMed
45.
Stanescu DE, Hughes N, Kaplan B, Stanley CA, de León DD. Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab. 2012;97(10):E2026–30.PubMedPubMedCentral
46.
Hamilton AJ, Bingham C, McDonald T, Cook PR, Caswell RC, Weedon MN, et al. The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a beta cell phenotype. J Med Genet. 2014;51(3):165–9.PubMed
47.
Numakura C, Hashimoto Y, Daitsu T, Hayasaka K, Mitsui T, Yorifuji T. Two patients with HNF4A-related congenital hyperinsulinism and renal tubular dysfunction: a clinical variation which includes transient hepatic dysfunction. Diabetes Res Clin Pract. 2015;108(3):e53–5.PubMed
48.
Walsh SB, Unwin R, Kleta R, van't Hoff W, Bass P, Hussain K, et al. Fainting Fanconi syndrome clarified by proxy: a case report. BMC Nephrol. 2017;18(1):230.PubMedPubMedCentral
49.
Rozenkova K, Malikova J, Nessa A, Dusatkova L, Bjørkhaug L, Obermannova B, et al. High incidence of heterozygous ABCC8 and HNF1A mutations in Czech patients with congenital Hyperinsulinism. J Clin Endocrinol Metab. 2015;100(12):E1540–9.PubMed
50.
Meissner T, Otonkoski T, Feneberg R, Beinbrech B, Apostolidou S, Sipilä I, et al. Exercise induced hypoglycaemic hyperinsulinism. Arch Dis Child. 2001;84(3):254–7.PubMedPubMedCentral
51.
Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, et al. Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells. Am J Hum Genet. 2007;81(3):467–74.PubMedPubMedCentral
52.
Meissner T, Friedmann B, Okun JG, Schwab MA, Otonkoski T, Bauer T, et al. Massive insulin secretion in response to anaerobic exercise in exercise-induced hyperinsulinism. Horm Metab Res. 2005;37(11):690–4.PubMed
53.
Fleury C, et al. Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet. 1997;15(3):269–72.PubMed
54.
González-Barroso MM, et al. Mutations in UCP2 in congenital hyperinsulinism reveal a role for regulation of insulin secretion. PLoS One. 2008;3(12):e3850.PubMedPubMedCentral
55.
Ferrara CT, Boodhansingh KE, Paradies E, Fiermonte G, Steinkrauss LJ, Topor LS, et al. Novel hypoglycemia phenotype in congenital Hyperinsulinism due to dominant mutations of uncoupling protein 2. J Clin Endocrinol Metab. 2017;102(3):942–9.PubMed
56.
Laver TW, Weedon MN, Caswell R, Hussain K, Ellard S, Flanagan SE. Analysis of large-scale sequencing cohorts does not support the role of variants in UCP2 as a cause of hyperinsulinaemic hypoglycaemia. Hum Mutat. 2017;38(10):1442–4.PubMedPubMedCentral
57.
Pinney SE, Ganapathy K, Bradfield J, Stokes D, Sasson A, Mackiewicz K, et al. Dominant form of congenital hyperinsulinism maps to HK1 region on 10q. Horm Res Paediatr. 2013;80(1):18–27.PubMed
58.
Henquin JC, Sempoux C, Marchandise J, Godecharles S, Guiot Y, Nenquin M, et al. Congenital hyperinsulinism caused by hexokinase I expression or glucokinase-activating mutation in a subset of β-cells. Diabetes. 2013;62(5):1689–96.PubMedPubMedCentral
59.
60.
Cabezas OR, Flanagan SE, Stanescu H, García-Martínez E, Caswell R, Lango-Allen H, et al. Polycystic kidney disease with Hyperinsulinemic hypoglycemia caused by a promoter mutation in Phosphomannomutase 2. J Am Soc Nephrol. 2017;28(8):2529–39.PubMedPubMedCentral
61.
Giri D, Vignola ML, Gualtieri A, Scagliotti V, McNamara P, Peak M, et al. Novel FOXA2 mutation causes Hyperinsulinism, hypopituitarism with craniofacial and endoderm-derived organ abnormalities. Hum Mol Genet. 2017;26(22):4315–26.PubMed
62.
Vajravelu ME, et al. Congenital Hyperinsulinism and hypopituitarism attributable to a mutation in FOXA2. J Clin Endocrinol Metab. 2018;103(3):1042–7.PubMedPubMedCentral
63.
Flanagan SE, Vairo F, Johnson MB, Caswell R, Laver TW, Lango Allen H, et al. A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. Pediatr Diabetes. 2017;18(4):320–3.PubMedPubMedCentral
64.
Gregory LC, Ferreira CB, Young-Baird SK, Williams HJ, Harakalova M, van Haaften G, et al. Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation. EBioMedicine. 2019;42:470–80.PubMedPubMedCentral
65.
Bufler P, Ehringhaus C, Koletzko S. Dumping syndrome: a common problem following Nissen fundoplication in young children. Pediatr Surg Int. 2001;17(5–6):351–5.PubMed
66.
Foster-Schubert KE. Hypoglycemia complicating bariatric surgery: incidence and mechanisms. Curr Opin Endocrinol Diabetes Obes. 2011;18(2):129–33.PubMedPubMedCentral
67.
Palladino AA, et al. Increased glucagon-like peptide-1 secretion and postprandial hypoglycemia in children after Nissen fundoplication. J Clin Endocrinol Metab. 2009;94(1):39–44.PubMed
68.
Hirata Y. Insulin autoimmune syndrome. Nihon Rinsho. 1973;31(7):2227–31.PubMed
69.
Shin JJ, Gorden P, Libutti SK. Insulinoma: pathophysiology, localization and management. Future Oncol. 2010;6(2):229–37.PubMedPubMedCentral
70.
Ozon A, Demirbilek H, Ertugrul A, Unal S, Gumruk F, Kandemir N. Anemia and neutropenic fever with high dose diazoxide treatment in a case with hyperinsulinism due to Munchausen by proxy. J Pediatr Endocrinol Metab. 2010;23(7):719–23.PubMed
71.
Toda N, Ihara K, Kojima-Ishii K, Ochiai M, Ohkubo K, Kawamoto Y, et al. Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and kabuki syndromes: a nationwide survey in Japan. Am J Med Genet A. 2017;173(2):360–7.PubMed
72.
Henquin JC, Nenquin M, Sempoux C, Guiot Y, Bellanné-Chantelot C, Otonkoski T, et al. In vitro insulin secretion by pancreatic tissue from infants with diazoxide-resistant congenital hyperinsulinism deviates from model predictions. J Clin Invest. 2011;121(10):3932–42.PubMedPubMedCentral
73.
Sempoux C, et al. Morphological Mosaicism of the pancreatic islets: a novel Anatomopathological form of persistent Hyperinsulinemic hypoglycemia of infancy. J Clin Endocrinol Metab. 2011;96(12):3785–93.PubMed
74.
Damaj L, le Lorch M, Verkarre V, Werl C, Hubert L, Nihoul-Fékété C, et al. Chromosome 11p15 paternal isodisomy in focal forms of neonatal hyperinsulinism. J Clin Endocrinol Metab. 2008;93(12):4941–7.PubMed
75.
Rahier J, Fält K, Müntefering H, Becker K, Gepts W, Falkmer S. The basic structural lesion of persistent neonatal hypoglycaemia with hyperinsulinism: deficiency of pancreatic D cells or hyperactivity of B cells? Diabetologia. 1984;26(4):282–9.PubMed
76.
Rahier J, Guiot Y, Sempoux C. Persistent hyperinsulinaemic hypoglycaemia of infancy: a heterogeneous syndrome unrelated to nesidioblastosis. Arch Dis Child Fetal Neonatal Ed. 2000;82(2):F108–12.PubMedPubMedCentral
77.
Goossens AGW. Saudubray JM, Bonnefont JP, Nihoul-Fekete, Heitz PU, Klöppel G., diffuse and focal nesidioblastosis. A clinicopathological study of 24 patients with persistent neonatal hyperinsulinemic hypoglycemia. Am J Surg Pathol. 1989;3(9):766–55.
78.
Sempoux C, et al. Neonatal hyperinsulinemic hypoglycemia: heterogeneity of the syndrome and keys for differential diagnosis. J Clin Endocrinol Metab. 1998;83(5):1455–61.PubMed
79.
Rahier J, et al. Partial or near-total pancreatectomy for persistent neonatal hyperinsulinaemic hypoglycaemia: the pathologist's role. Histopathology. 1998;32(1):15–9.PubMed
80.
Otonkoski T, et al. Noninvasive diagnosis of focal Hyperinsulinism of infancy with [18F]-DOPA positron emission tomography. Diabetes. 2006;55(1):13–8.PubMed
81.
Sempoux C, Guiot Y, Jaubert F, Rahier J. Focal and diffuse forms of congenital hyperinsulinism: the keys for differential diagnosis. Endocr Pathol. 2004;15(3):241–6.PubMed
82.
Hussain K, et al. An ABCC8 gene mutation and mosaic uniparental isodisomy resulting in atypical diffuse congenital hyperinsulinism. Diabetes. 2008;57(1):259–63.PubMed
83.
Henquin JC, Sempoux C, Marchandise J, Godecharles S, Guiot Y, Nenquin M, et al. Congenital hyperinsulinism caused by hexokinase I expression or glucokinase-activating mutation in a subset of beta-cells. Diabetes. 2013;62(5):1689–96.PubMedPubMedCentral
84.
Shi Y, Avatapalle HB, Skae MS, Padidela R, Newbould M, Rigby L, et al. Increased plasma Incretin concentrations identifies a subset of patients with persistent congenital Hyperinsulinism without KATP Channel gene defects. J Pediatr. 2015;166(1):191–4.PubMed
85.
Hussain K. Investigations for neonatal hypoglycaemia. Clin Biochem. 2011;44(7):465–6.PubMed
86.
Aynsley-Green A, Hussain K, Hall J, Saudubray JM, Nihoul-Fékété C, de Lonlay-Debeney P, et al. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal Ed. 2000;82(2):F98–F107.PubMedPubMedCentral
87.
Yorifuji T, Horikawa R, Hasegawa T, Adachi M, Soneda S, Minagawa M, et al. Clinical practice guidelines for congenital hyperinsulinism. Clin Pediatr Endocrinol. 2017;26(3):127–52.PubMedPubMedCentral
88.
Palladino AA, Bennett MJ, Stanley CA. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Clin Chem. 2008;54(2):256–63.PubMed
89.
Al-Otaibi H, et al. Biochemical studies in patients with hyperinsulinaemic hypoglycaemia. Eur J Pediatr. 2013;172(11):1435–40.PubMed
90.
Ferrara C, et al. Biomarkers of insulin for the diagnosis of Hyperinsulinemic hypoglycemia in infants and children. J Pediatr. 2016;168:212–9.
91.
Brun JF, Fédou C, Bouix O, Raynaud E, Orsetti A. Evaluation of a standardized hyperglucidic breakfast test in postprandial reactive hypoglycaemia. Diabetologia. 1995;38(4):494–501.PubMed
92.
Otonkoski T, Kaminen N, Ustinov J, Lapatto R, Meissner T, Mayatepek E, et al. Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant trait characterized by abnormal pyruvate-induced insulin release. Diabetes. 2003;52(1):199–204.PubMed
93.
Alsaffar H, et al. Continuous flash glucose monitoring in children with congenital Hyperinsulinism; first report on accuracy and patient experience. Int J Pediatr Endocrinol. 2018;2018:3.PubMedPubMedCentral
94.
Meintjes M, Endozo R, Dickson J, Erlandsson K, Hussain K, Townsend C, et al. 18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective. Nucl Med Commun. 2013;34(6):601–8.PubMed
95.
Lord K, et al. Clinical presentation and management of children with diffuse and focal hyperinsulinism: a review of 223 cases. J Clin Endocrinol Metab. 2013;98(11):E1786–9.PubMedPubMedCentral
96.
Blomberg BA, et al. The value of radiologic interventions and (18)F-DOPA PET in diagnosing and localizing focal congenital hyperinsulinism: systematic review and meta-analysis. Mol Imaging Biol. 2013;15(1):97–105.PubMed
97.
Ismail D, Kapoor RR, Smith VV, Ashworth M, Blankenstein O, Pierro A, et al. The heterogeneity of focal forms of congenital hyperinsulinism. J Clin Endocrinol Metab. 2012;97(1):E94–9.PubMed
98.
Hardy OT, et al. Accuracy of [18F]fluorodopa positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2007;92(12):4706–11.PubMed
99.
Banerjee I, Avatapalle B, Padidela R, Stevens A, Cosgrove KE, Clayton PE, et al. Integrating genetic and imaging investigations into the clinical management of congenital hyperinsulinism. Clin Endocrinol. 2013;78(6):803–13.
100.
Ribeiro MJ, Boddaert N, Delzescaux T, Valayannopoulos V, Bellanné-Chantelot C, Jaubert F, et al. Functional imaging of the pancreas: the role of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy. Endocr Dev. 2007;12:55–66.PubMed
101.
Barthlen W, et al. Evaluation of [18F]fluoro-L-DOPA positron emission tomography-computed tomography for surgery in focal congenital hyperinsulinism. J Clin Endocrinol Metab. 2008;93(3):869–75.PubMed
102.
Zani A, et al. The predictive value of preoperative fluorine-18-L-3,4-dihydroxyphenylalanine positron emission tomography-computed tomography scans in children with congenital hyperinsulinism of infancy. J Pediatr Surg. 2011;46(1):204–8.PubMed
103.
Capito C, Khen-Dunlop N, Ribeiro MJ, Brunelle F, Aigrain Y, Crétolle C, et al. Value of 18F-fluoro-L-dopa PET in the preoperative localization of focal lesions in congenital hyperinsulinism. Radiology. 2009;253(1):216–22.PubMed
104.
Treglia G, Mirk P, Giordano A, Rufini V. Diagnostic performance of fluorine-18-dihydroxyphenylalanine positron emission tomography in diagnosing and localizing the focal form of congenital hyperinsulinism: a meta-analysis. Pediatr Radiol. 2012;42(11):1372–9.PubMed
105.
Garg PK, et al. Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism. PLoS One. 2017;12(11):e0186340.PubMedPubMedCentral
106.
Maines E, Giacomello L, D'Onofrio M, Salgarello M, Gaudino R, Baggio L, et al. Images from. Nucl Med Mol Imaging. 2017;51(4):362–3.PubMed
107.
Kühnen P, Matthae R, Arya V, Hauptmann K, Rothe K, Wächter S, et al. Occurrence of giant focal forms of congenital hyperinsulinism with incorrect visualization by (18) F DOPA-PET/CT scanning. Clin Endocrinol. 2014;81(6):847–54.
108.
Parihar AS, et al. 68Ga DOTA-Exendin PET/CT for detection of Insulinoma in a patient with persistent Hyperinsulinemic hypoglycemia. Clin Nucl Med. 2018;43(8):e285–e286.
109.
Cuthbertson DJ, Banks M, Khoo B, Antwi K, Christ E, Campbell F, et al. Application of Ga(68) -DOTA-exendin-4 PET/CT to localize an occult insulinoma. Clin Endocrinol. 2016;84(5):789–91.
110.
Tuzcu SA, Pekkolay Z, Kılınç F, Tuzcu AK. Ga-DOTATATE PET/CT can be an alternative imaging method in Insulinoma patients. J Nucl Med Technol. 2017;45(3):198–200.PubMed
111.
Deppen SA, Blume J, Bobbey AJ, Shah C, Graham MM, Lee P, et al. 68Ga-DOTATATE compared with 111In-DTPA-Octreotide and conventional imaging for pulmonary and Gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis. J Nucl Med. 2016;57(6):872–8.PubMedPubMedCentral
112.
Sharma P, et al. Somatostatin receptor based PET/CT imaging with 68Ga-DOTA-Nal3-octreotide for localization of clinically and biochemically suspected insulinoma. Q J Nucl Med Mol Imaging. 2016;60(1):69–76.PubMed
113.
Hussain K, Blankenstein O, de Lonlay P, Christesen HT. Hyperinsulinaemic hypoglycaemia: biochemical basis and the importance of maintaining normoglycaemia during management. Arch Dis Child. 2007;92(7):568–70.PubMedPubMedCentral
114.
Nebesio TD, Hoover WC, Caldwell RL, Nitu ME, Eugster EA. Development of pulmonary hypertension in an infant treated with diazoxide. J Pediatr Endocrinol Metab. 2007;20(8):939–44.
115.
Timlin MR, Black AB, Delaney HM, Matos RI, Percival CS. Development of pulmonary hypertension during treatment with Diazoxide: a case series and literature review. Pediatr Cardiol. 2017;38(6):1247–50.
116.
Chen SC, Dastamani A, Pintus D, Yau D, Aftab S, Bath L, et al. Diazoxide‐induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: Recommendations from a multicentre study in the United Kingdom. Clin Endocrinol. 2019;91(6):770–775.
117.
118.
Müller D, Zimmering M, Roehr CC. Should nifedipine be used to counter low blood sugar levels in children with persistent hyperinsulinaemic hypoglycaemia? Arch Dis Child. 2004;89(1):83–5.PubMedPubMedCentral
119.
Baş F, et al. Successful therapy with calcium channel blocker (nifedipine) in persistent neonatal hyperinsulinemic hypoglycemia of infancy. J Pediatr Endocrinol Metab. 1999;12(6):873–8.PubMed
120.
Shanbag P, Pathak A, Vaidya M, Shahid SK. Persistent hyperinsulinemic hypoglycemia of infancy--successful therapy with nifedipine. Indian J Pediatr. 2002;69(3):271–2.PubMed
121.
Eichmann D, Hufnagel M, Quick P, Santer R. Treatment of hyperinsulinaemic hypoglycaemia with nifedipine. Eur J Pediatr. 1999;158(3):204–6.PubMed
122.
Welters A, et al. Long-term medical treatment in congenital hyperinsulinism: a descriptive analysis in a large cohort of patients from different clinical centers. Orphanet J Rare Dis. 2015;10:150.PubMedPubMedCentral
123.
Güemes M, Shah P, Silvera S, Morgan K, Gilbert C, Hinchey L, et al. Assessment of Nifedipine therapy in Hyperinsulinemic hypoglycemia due to mutations in the ABCC8 gene. J Clin Endocrinol Metab. 2017;102(3):822–30.PubMed
124.
Durmaz E, Flanagan SE, Parlak M, Ellard S, Akcurin S, Bircan I. A combination of nifedipine and octreotide treatment in an hyperinsulinemic hypoglycemic infant. J Clin Res Pediatr Endocrinol. 2014;6(2):119–21.PubMedPubMedCentral
125.
Glaser B, Hirsch HJ, Landau H. Persistent hyperinsulinemic hypoglycemia of infancy: long-term octreotide treatment without pancreatectomy. J Pediatr. 1993;123(4):644–50.PubMed
126.
Thornton PS, Alter CA, Katz LE, Baker L, Stanley CA. Short- and long-term use of octreotide in the treatment of congenital hyperinsulinism. J Pediatr. 1993;123(4):637–43.PubMed
127.
Roženková K, et al. The diagnosis and Management of Hyperinsulinaemic Hypoglycaemia. J Clin Res Pediatr Endocrinol. 2015;7(2):86–97.PubMedPubMedCentral
128.
Mohnike K, Blankenstein O, Pfuetzner A, Pötzsch S, Schober E, Steiner S, et al. Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon. Horm Res. 2008;70(1):59–64.PubMed
129.
Brun JF, Fedou C, Mercier J. Postprandial reactive hypoglycemia. Diabetes Metab. 2000;26(5):337–51.PubMed
130.
Salvatore T, Giugliano D. Pharmacokinetic-pharmacodynamic relationships of Acarbose. Clin Pharmacokinet. 1996;30(2):94–106.PubMed
131.
Le Quan Sang KH, et al. Successful treatment of congenital hyperinsulinism with long-acting release octreotide. Eur J Endocrinol. 2012;166(2):333–9.PubMed
132.
Modan-Moses D, Koren I, Mazor-Aronovitch K, Pinhas-Hamiel O, Landau H. Treatment of congenital hyperinsulinism with lanreotide acetate (Somatuline autogel). J Clin Endocrinol Metab. 2011;96(8):2312–7.PubMed
133.
Shah P, Rahman SA, McElroy S, Gilbert C, Morgan K, Hinchey L, et al. Use of long-acting Somatostatin analogue (Lanreotide) in an adolescent with Diazoxide-responsive congenital Hyperinsulinism and its psychological impact. Horm Res Paediatr. 2015;84(5):355–60.PubMed
134.
Kühnen P, et al. Long-term lanreotide treatment in six patients with congenital hyperinsulinism. Horm Res Paediatr. 2012;78(2):106–12.PubMed
135.
van der Steen I, van Albada M, Mohnike K, Christesen HT, Empting S, Salomon-Estebanez M, et al. A multicenter experience with long-acting Somatostatin analogues in patients with congenital Hyperinsulinism. Horm Res Paediatr. 2018;89(2):82–9.PubMed
136.
Corda H, et al. Treatment with long-acting lanreotide autogel in early infancy in patients with severe neonatal hyperinsulinism. Orphanet J Rare Dis. 2017;12(1):108.PubMedPubMedCentral
137.
Dastamani A, Güemes M, Pitfield C, Morgan K, Rajab M, Rottenburger C, et al. The use of a long-acting Somatostatin analogue (Lanreotide) in three children with focal forms of congenital Hyperinsulinaemic Hypoglycaemia. Horm Res Paediatr. 2019;91(1):56–61.PubMed
138.
Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med. 2009;360(2):195–7.PubMed
139.
Alexandrescu S, et al. Persistent hyperinsulinemic hypoglycemia of infancy: constitutive activation of the mTOR pathway with associated exocrine-islet transdifferentiation and therapeutic implications. Int J Clin Exp Pathol. 2010;3(7):691–705.PubMedPubMedCentral
140.
Senniappan S, Alexandrescu S, Tatevian N, Shah P, Arya V, Flanagan S, et al. Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia. N Engl J Med. 2014;370(12):1131–7.PubMed
141.
Guemes M, et al. Severe Hyperinsulinaemic Hypoglycaemia in Beckwith-Wiedemann syndrome due to paternal Uniparental Disomy of 11p15.5 managed with Sirolimus therapy. Horm Res Paediatr. 2016;85(5):353–7.PubMed
142.
Shah P, Arya VB, Flanagan SE, Morgan K, Ellard S, Senniappan S, et al. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation. J Pediatr Endocrinol Metab. 2015;28(5–6):695–9.PubMed
143.
Al-Balwi R, et al. Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism. J Pediatr Endocrinol Metab. 2017;30(9):1013–7.PubMed
144.
Minute M, et al. Sirolimus therapy in congenital Hyperinsulinism: a successful experience beyond infancy. Pediatrics. 2015;136(5):e1373–6.PubMed
145.
Méder Ü, et al. Severe Hyperinsulinemic hypoglycemia in a neonate: response to Sirolimus therapy. Pediatrics. 2015;136(5):e1369–72.PubMed
146.
Haliloğlu B, Tüzün H, Flanagan SE, et al. Sirolimus-Induced hepatitis in two patients with hyperinsulinemic hypoglycemia. J Clin Res Pediatr Endocrinol. 2018;10(3):279–283.
147.
Dastamani A, Güemes M, Walker J, Shah P, Hussain K. Sirolimus precipitating diabetes mellitus in a patient with congenital hyperinsulinaemic hypoglycaemia due to autosomal dominant ABCC8 mutation. J Pediatr Endocrinol Metab. 2017;30(11):1219–22.PubMed
148.
Szymanowski M, Estebanez MS, Padidela R, Han B, Mosinska K, Stevens A, et al. mTOR inhibitors for the treatment of severe congenital Hyperinsulinism: perspectives on limited therapeutic success. J Clin Endocrinol Metab. 2016;101(12):4719–29.PubMed
149.
Banerjee I, De Leon D, Dunne MJ. Extreme caution on the use of sirolimus for the congenital hyperinsulinism in infancy patient. Orphanet J Rare Dis. 2017;12(1):70.PubMedPubMedCentral
150.
Maria G, Antonia D, Michael A, Kate M, Sian E, Sarah FE, et al. Sirolimus: efficacy and complications in children with Hyperinsulinemic hypoglycemia: a 5-year follow-up study. J Endocr Soc. 2019;3(4):699–713.PubMedPubMedCentral
151.
McClenaghan NH, Flatt PR, Ball AJ. Actions of glucagon-like peptide-1 on KATP channel-dependent and -independent effects of glucose, sulphonylureas and nateglinide. J Endocrinol. 2006;190(3):889–96.PubMed
152.
De León DD, et al. Exendin-(9-39) corrects fasting hypoglycemia in SUR-1−/− mice by lowering cAMP in pancreatic beta-cells and inhibiting insulin secretion. J Biol Chem. 2008;283(38):25786–93.PubMedPubMedCentral
153.
Calabria AC, Li C, Gallagher PR, Stanley CA, de León DD. GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel. Diabetes. 2012;61(10):2585–91.PubMedPubMedCentral
154.
Chen PC, Olson EM, Zhou Q, Kryukova Y, Sampson HM, Thomas DY, et al. Carbamazepine as a novel small molecule corrector of trafficking-impaired ATP-sensitive potassium channels identified in congenital hyperinsulinism. J Biol Chem. 2013;288(29):20942–54.PubMedPubMedCentral
155.
Yan F, Lin CW, Weisiger E, Cartier EA, Taschenberger G, Shyng SL. Sulfonylureas correct trafficking defects of ATP-sensitive potassium channels caused by mutations in the sulfonylurea receptor. J Biol Chem. 2004;279(12):11096–105.PubMed
156.
Devaraneni PK, Martin GM, Olson EM, Zhou Q, Shyng SL. Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism. J Biol Chem. 2015;290(12):7980–91.PubMedPubMedCentral
157.
Martin GM, Rex EA, Devaraneni P, Denton JS, Boodhansingh KE, DeLeon D, et al. Pharmacological correction of trafficking defects in ATP-sensitive potassium channels caused by sulfonylurea receptor 1 mutations. J Biol Chem. 2016;291(42):21971–83.PubMedPubMedCentral
158.
Neylon OM, Moran MM, Pellicano A, Nightingale M, O'Connell MA. Successful subcutaneous glucagon use for persistent hypoglycaemia in congenital hyperinsulinism. J Pediatr Endocrinol Metab. 2013;26(11–12):1157–61.PubMed
159.
Hövelmann U, Bysted BV, Mouritzen U, Macchi F, Lamers D, Kronshage B, et al. Pharmacokinetic and Pharmacodynamic characteristics of Dasiglucagon, a novel soluble and stable glucagon analog. Diabetes Care. 2018;41(3):531–7.PubMed
160.
Laguna Sanz AJ, Mulla CM, Fowler KM, Cloutier E, Goldfine AB, Newswanger B, et al. Design and clinical evaluation of a novel low-glucose prediction algorithm with mini-dose stable glucagon delivery in post-bariatric hypoglycemia. Diabetes Technol Ther. 2018;20(2):127–39.PubMedPubMedCentral
161.
Pierro A, Nah SA. Surgical management of congenital hyperinsulinism of infancy. Semin Pediatr Surg. 2011;20(1):50–3.PubMed
162.
Adzick NS, Thornton PS, Stanley CA, Kaye RD, Ruchelli E. A multidisciplinary approach to the focal form of congenital hyperinsulinism leads to successful treatment by partial pancreatectomy. J Pediatr Surg. 2004;39(3):270–5.PubMed
163.
Al-Shanafey S. Laparoscopic vs open pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy. J Pediatr Surg. 2009;44(5):957–61.PubMed
164.
Laje P, et al. Pancreatic head resection and roux-en-Y pancreaticojejunostomy for the treatment of the focal form of congenital hyperinsulinism. J Pediatr Surg. 2012;47(1):130–5.PubMedPubMedCentral
165.
Beltrand J, Caquard M, Arnoux JB, Laborde K, Velho G, Verkarre V, et al. Glucose metabolism in 105 children and adolescents after pancreatectomy for congenital hyperinsulinism. Diabetes Care. 2012;35(2):198–203.PubMedPubMedCentral
166.
Arya VB, Senniappan S, Demirbilek H, Alam S, Flanagan SE, Ellard S, et al. Pancreatic endocrine and exocrine function in children following near-total pancreatectomy for diffuse congenital hyperinsulinism. PLoS One. 2014;9(5):e98054.PubMedPubMedCentral
167.
Shah P, Demirbilek H, Hussain K. Persistent hyperinsulinaemic hypoglycaemia in infancy. Semin Pediatr Surg. 2014;23(2):76–82.PubMed
168.
Gouya H, Vignaux O, Augui J, Dousset B, Palazzo L, Louvel A, et al. CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas. AJR Am J Roentgenol. 2003;181(4):987–92.PubMed
169.
Iglesias P, Lafuente C, Martín Almendra MÁ, López Guzmán A, Castro JC, Díez JJ. Insulinoma: a multicenter, retrospective analysis of three decades of experience (1983-2014). Endocrinol Nutr. 2015;62(7):306–13.PubMed
170.
Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, et al. Diagnosis and management of insulinoma. World J Gastroenterol. 2013;19(6):829–37.PubMedPubMedCentral
171.
Antonakis PT, Ashrafian H, Martinez-Isla A. Pancreatic insulinomas: laparoscopic management. World J Gastrointest Endosc. 2015;7(16):1197–207.PubMedPubMedCentral
172.
Ito T, Igarashi H, Jensen RT. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances. Best Pract Res Clin Gastroenterol. 2012;26(6):737–53.PubMedPubMedCentral
173.
Salomon-Estebanez M, Flanagan SE, Ellard S, Rigby L, Bowden L, Mohamed Z, et al. Conservatively treated congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time. Orphanet J Rare Dis. 2016;11(1):163.PubMedPubMedCentral
174.
Sun L, Coy DH. Somatostatin and its analogs. Curr Drug Targets. 2016;17(9):529–537.
175.
Demirbilek H, Shah P, Arya VB, Hinchey L, Flanagan SE, Ellard S, et al. Long-term follow-up of children with congenital hyperinsulinism on octreotide therapy. J Clin Endocrinol Metab. 2014;99(10):3660–7.PubMed
176.
Lord K, et al. High risk of diabetes and neurobehavioral deficits in individuals with surgically treated Hyperinsulinism. J Clin Endocrinol Metab. 2015;100(11):4133–9.PubMedPubMedCentral
177.
Ludwig A, et al. Formal neurocognitive testing in 60 patients with congenital Hyperinsulinism. Horm Res Paediatr. 2018;89(1):1–6.PubMed
178.
179.
Lotstein DS, et al. Transition from pediatric to adult care for youth diagnosed with type 1 diabetes in adolescence. Pediatrics. 2013;131(4):e1062–70.PubMedPubMedCentral
180.
Viner R. Transition from paediatric to adult care. Bridging the gaps or passing the buck? Arch Dis Child. 1999;81(3):271–5.PubMedPubMedCentral
181.
Zhou H, Roberts P, Dhaliwal S, Della P. Transitioning adolescent and young adults with chronic disease and/or disabilities from paediatric to adult care services - an integrative review. J Clin Nurs. 2016;25(21–22):3113–30.PubMedPubMedCentral
182.
de Silva PS, Fishman LN. Transition of the patient with IBD from pediatric to adult care-an assessment of current evidence. Inflamm Bowel Dis. 2014;20(8):1458–64.PubMed
183.
Borus JS, Laffel L. Adherence challenges in the management of type 1 diabetes in adolescents: prevention and intervention. Curr Opin Pediatr. 2010;22(4):405–11.PubMedPubMedCentral
184.
Valenzuela JM, Buchanan CL, Radcliffe J, Ambrose C, Hawkins LA, Tanney M, et al. Transition to adult services among behaviorally infected adolescents with HIV--a qualitative study. J Pediatr Psychol. 2011;36(2):134–40.PubMed
185.
Hanna KM, Woodward J. The transition from pediatric to adult diabetes care services. Clin Nurse Spec. 2013;27(3):132–45.PubMedPubMedCentral
186.
van Staa A, Sattoe JN. Young adults' experiences and satisfaction with the transfer of care. J Adolesc Health. 2014;55(6):796–803.PubMed
187.
Barlow J, et al. Self-management approaches for people with chronic conditions: a review. Patient Educ Couns. 2002;48(2):177–87.PubMed
188.
Acuña Mora M, Sparud-Lundin C, Bratt EL, Moons P. Person-centred transition programme to empower adolescents with congenital heart disease in the transition to adulthood: a study protocol for a hybrid randomised controlled trial (STEPSTONES project). BMJ Open. 2017;7(4):e014593.PubMedPubMedCentral
189.
190.
Peters A, Laffel L, A.D.A.T.W. Group. Diabetes care for emerging adults: recommendations for transition from pediatric to adult diabetes care systems: a position statement of the American Diabetes Association, with representation by the American College of Osteopathic Family Physicians, the American Academy of Pediatrics, the American Association of Clinical Endocrinologists, the American Osteopathic Association, the Centers for Disease Control and Prevention, Children with Diabetes, The Endocrine Society, the International Society for Pediatric and Adolescent Diabetes, Juvenile Diabetes Research Foundation International, the National Diabetes Education Program, and the Pediatric Endocrine Society (formerly Lawson Wilkins Pediatric Endocrine Society). Diabetes Care. 2011;34(11):2477–85.PubMedPubMedCentral
191.
Choudhary P, Amiel SA. Hypoglycaemia in type 1 diabetes: technological treatments, their limitations and the place of psychology. Diabetologia. 2018;61(4):761–9.PubMedPubMedCentral
192.
Clarke WL, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W. Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care. 1995;18(4):517–22.PubMed
193.
Gold AE, MacLeod KM, Frier BM. Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care. 1994;17(7):697–703.PubMed
194.
Hay WW, et al. Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development. J Pediatr. 2009;155(5):612–7.PubMed
195.
DVLA Assessing fitness to drive – a guide for medical. professionals [Internet]. May 20, 2018.
196.
197.
Rosenbaum P, Stewart D. Perspectives on transitions: rethinking services for children and youth with developmental disabilities. Arch Phys Med Rehabil. 2007;88(8):1080–2.PubMed
198.
Cannarella R, Arato I, Condorelli RA, et al. Effects of insulin on porcine neonatal sertoli cell responsiveness to FSH In Vitro. J Clin Med. 2019;8(6):809.
199.
Garvey KC, Wolpert HA, Laffel LM, Rhodes ET, Wolfsdorf JI, Finkelstein JA. Health care transition in young adults with type 1 diabetes: barriers to timely establishment of adult diabetes care. Endocr Pract. 2013;19(6):946–52.PubMedPubMedCentral
200.
Johnson SR, Leo PJ, McInerney-Leo A, Anderson LK, Marshall M, McGown I, et al. Whole-exome sequencing for mutation detection in pediatric disorders of insulin secretion: maturity onset diabetes of the young and congenital hyperinsulinism. Pediatr Diabetes. 2018;19(4):656–62.PubMed
201.
Shah P, et al. Hyperinsulinaemic hypoglycaemia in children and adults. Lancet Diabetes Endocrinol. 2017;5(9):729–42.PubMed
202.
Corbin JA, Bhaskar V, Goldfine ID, Issafras H, Bedinger DH, Lau A, et al. Inhibition of insulin receptor function by a human, allosteric monoclonal antibody: a potential new approach for the treatment of hyperinsulinemic hypoglycemia. MAbs. 2014;6(1):262–72.PubMed
203.
Kapoor RR, James C, Hussain K. Hyperinsulinism in developmental syndromes. Endocr Dev. 2009;14:95–113.PubMed
Metadata
Title
Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management
Authors
Maria Gϋemes
Sofia Asim Rahman
Ritika R. Kapoor
Sarah Flanagan
Jayne A. L. Houghton
Shivani Misra
Nick Oliver
Mehul Tulsidas Dattani
Pratik Shah
Publication date
01-12-2020
Publisher
Springer US
Published in
Reviews in Endocrine and Metabolic Disorders / Issue 4/2020
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI
https://doi.org/10.1007/s11154-020-09548-7

Other articles of this Issue 4/2020

Reviews in Endocrine and Metabolic Disorders 4/2020 Go to the issue

ReviewPaper

Clinical manifestations and management of fatty acid oxidation disorders

ReviewPaper

Serotonin pathway in carcinoid syndrome: Clinical, diagnostic, prognostic and therapeutic implications

ReviewPaper

Associations between body mass index, waist circumference and erectile dysfunction: a systematic review and META-analysis

ReviewPaper

The use of Broca index to assess cut- off points for overweight in adults: A short review

ReviewPaper

Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis

Correction

Correction to: Diet approach before and after bariatric surgery
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits