1
|
Giri D, Hawton K, Senniappan S. Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management. J Pediatr Endocrinol Metab 2022; 35:279-296. [PMID: 34547194 DOI: 10.1515/jpem-2021-0369] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/30/2021] [Indexed: 12/20/2022]
Abstract
Congenital hyperinsulinism (CHI) is a rare disease characterized by an unregulated insulin release, leading to hypoglycaemia. It is the most frequent cause of persistent and severe hypoglycaemia in the neonatal period and early childhood. Mutations in 16 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, KCNQ1, CACNA1D, FOXA2, EIF2S3, PGM1 and PMM2) that are involved in regulating the insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms of CHI. CHI can also be associated with specific syndromes and can be secondary to intrauterine growth restriction (IUGR), maternal diabetes, birth asphyxia, etc. It is important to diagnose and promptly initiate appropriate management as untreated hypoglycaemia can be associated with significant neurodisability. CHI can be histopathologically classified into diffuse, focal and atypical forms. Advances in molecular genetics, imaging techniques (18F-fluoro-l-dihydroxyphenylalanine positron emission tomography/computed tomography scanning), novel medical therapies and surgical advances (laparoscopic pancreatectomy) have changed the management and improved the outcome of patients with CHI. This review article provides an overview of the background, clinical presentation, diagnosis, molecular genetics and therapy for children with different forms of CHI.
Collapse
Affiliation(s)
- Dinesh Giri
- Bristol Royal Hospital for Children, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK.,University of Bristol, Bristol, UK
| | - Katherine Hawton
- Bristol Royal Hospital for Children, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | | |
Collapse
|
2
|
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.
Collapse
Affiliation(s)
- Hüseyin Demirbilek
- Hacettepe University Faculty of Medicine, Department of Paediatric Endocrinology, Ankara, Turkey
| | - Khalid Hussain
- Sidra Medical and Research Center, Clinic of Paediatric Medicine, Doha, Qatar
,* Address for Correspondence: Sidra Medical and Research Center, Clinic of Paediatric Medicine, Doha, Qatar Phone: +974-30322007 E-mail:
| |
Collapse
|
3
|
Demirbilek H, Rahman SA, Buyukyilmaz GG, Hussain K. Diagnosis and treatment of hyperinsulinaemic hypoglycaemia and its implications for paediatric endocrinology. INTERNATIONAL JOURNAL OF PEDIATRIC ENDOCRINOLOGY 2017; 2017:9. [PMID: 28855921 PMCID: PMC5575922 DOI: 10.1186/s13633-017-0048-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Accepted: 08/15/2017] [Indexed: 12/14/2022]
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.
Collapse
Affiliation(s)
- Huseyin Demirbilek
- Department of Paediatric Endocrinology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
| | - Sofia A Rahman
- Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, 30 Guilford Street, London, WC1N 1EH UK
| | - Gonul Gulal Buyukyilmaz
- Department of Paediatric Endocrinology, Hacettepe University, Faculty of Medicine, Ankara, Turkey
| | - Khalid Hussain
- Department of Paediatric Medicine Sidra Medical & Research Center, OPC, C6-337, PO Box 26999, Doha, Qatar
| |
Collapse
|
4
|
Gopal-Kothandapani JS, Hussain K. Congenital hyperinsulinism: Role of fluorine-18L-3, 4 hydroxyphenylalanine positron emission tomography scanning. World J Radiol 2014; 6:252-260. [PMID: 24976928 PMCID: PMC4072812 DOI: 10.4329/wjr.v6.i6.252] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Revised: 03/19/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Congenital hyperinsulinism (CHI) is a rare but complex heterogeneous disorder caused by unregulated secretion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift diagnosis and institution of appropriate management is crucial to prevent or minimise adverse neurodevelopmental outcome in children with CHI. Histologically there are two major subtypes of CHI, diffuse and focal disease and the management approach will significantly differ depending on the type of the lesion. Patients with medically unresponsive diffuse disease require a near total pancreatectomy, which then leads on to the development of iatrogenic diabetes mellitus and pancreatic exocrine insufficiency. However patients with focal disease only require a limited pancreatectomy to remove only the focal lesion thus providing complete cure to the patient. Hence the preoperative differentiation of the histological subtypes of CHI becomes paramount in the management of CHI. Fluorine-18L-3, 4-hydroxyphenylalanine positron emission tomography (18F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and localisation of the focal lesion. The aim of this review article is to give a clinical overview of CHI, then review the role of dopamine in β-cell physiology and finally discuss the role of 18F-DOPA-PET imaging in the management of CHI.
Collapse
|
5
|
Abstract
A male patient was born small for gestational age (SGA) at 33 weeks with a birth weight of 1,663 grams (< 10th percentile) and length 43 cm (10th percentile) to a 38-year-old G5P4 mother by cesarean section due to non-reassuring fetal heart tones. Prior to delivery, his mother experienced decreased fetal movement and decelerations. At birth, he was initially well-appearing and vigorous, with Apgar scores of 7 and 8 at 1 and 5 minutes, respectively. The physical examination was unremarkable--no skin findings, no facial anomalies, good tone, and the anterior fontanelle was soft and flat. The placenta, although noted to be healthy in appearance on prenatal ultrasounds, was atrophic and calcified by gross examination. The patient developed respiratory distress 1 hour after birth and was found to have a blood glucose level of 24 mg/dL. Following an intravenous (IV) bolus of 10% dextrose in water (D10W) of 2 mL/kg, his glucose was 20 mg/dL. He was started on IV fluids with a glucose infusion rate (GIR) of 7.3 mg/kg/minute, with a subsequent rise in blood glucose to 46 mg/dL. Due to prematurity, respiratory distress, and persistent hypoglycemia, a diagnostic evaluation was initiated for possible sepsis, including a complete blood count with differential and platelet count and blood cultures. The patient was started empirically on IV ampicillin and gentamicin. The patient was subsequently found to have thrombocytopenia, hypomagnesemia, and hyponatremia on laboratory evaluation and was transferred to our neonatal intensive care unit (NICU) for further care.
Collapse
|
6
|
Mohamed Z, Arya VB, Hussain K. Hyperinsulinaemic hypoglycaemia:genetic mechanisms, diagnosis and management. J Clin Res Pediatr Endocrinol 2012; 4:169-81. [PMID: 23032149 PMCID: PMC3537282 DOI: 10.4274/jcrpe.821] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Hyperinsulinaemic hypoglycaemia (HH) is characterized by unregulated insulin secretion from pancreatic β-cells. Untreated hypoglycaemia in infants can lead to seizures, developmental delay, and subsequent permanent brain injury. Early identification and meticulous managementof these patients is vital to prevent neurological insult. Mutations in eight different genes (ABCC8, KCNJ11, GLUD1, CGK, HADH, SLC16A1, HNF4A and UCP2) have been identified to date in patients with congenital forms of hyperinsulinism (CHI). The most severe forms of CHI are due to mutations in ABCC8 and KCJN11, which encode the two components of pancreatic β-cell ATP-sensitive potassium channel. Recent advancement in understanding the genetic aetiology, histological characterisation into focal and diffuse variety combined with improved imaging (such as fluorine 18 L-3, 4-dihydroxyphenylalanine positron emission tomography 18F-DOPA-PET scanning) and laparoscopic surgical techniques have greatly improved management. In adults, HH can be due to an insulinoma, pancreatogenous hypoglycaemic syndrome, post gastric-bypass surgery for morbid obesity as well as to mutations in insulin receptor gene. This review provides an overview of the molecular basis of CHI and outlines the clinical presentation, diagnostic criteria, and management of these patients.
Collapse
Affiliation(s)
- Zainaba Mohamed
- University College London, Institue of Child Health, Developmental Endocrinology Research Clinical, Molecular Genetics Unit, London, United Kingdom
| | - Ved Bhushan Arya
- University College London, Institue of Child Health, Developmental Endocrinology Research Clinical, Molecular Genetics Unit, London, United Kingdom
| | - Khalid Hussain
- University College London, Institue of Child Health, Developmental Endocrinology Research Clinical, Molecular Genetics Unit, London, United Kingdom
,* Address for Correspondence: Khalid Hussain MD, University College London, Institue of Child Health, Developmental Endocrinology Research Clinical, Molecular Genetics Unit, London, United Kingdom Phone: +44 207 905 2128 E-mail:
| |
Collapse
|
7
|
Hewitt V, Watts R, Robertson J, Haddow G. Nursing and midwifery management of hypoglycaemia in healthy term neonates. INT J EVID-BASED HEA 2012; 3:169-205. [PMID: 21631748 DOI: 10.1111/j.1479-6988.2005.00025.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
UNLABELLED EXECUTIVE SUMMARY: OBJECTIVES The primary objective of this review was to determine the best available evidence for maintenance of euglycaemia* in healthy term neonates, and the management of asymptomatic hypoglycaemia in otherwise healthy term neonates. INCLUSION CRITERIA TYPES OF STUDIES: The review included any relevant published or unpublished studies undertaken between 1995 and 2004. Studies that focus on the diagnostic accuracy of point-of-care devices for blood glucose screening and/or monitoring in the neonate were initially included as a subgroup of this review. However, the technical nature and complexity of the statistical information published in diagnostic studies retrieved during the literature search stage, as well as the considerable volume of published research in this area, suggested that it would be more feasible to analyse diagnostic studies in a separate systematic review. TYPES OF PARTICIPANTS The review focused on studies that included healthy term (37- to 42-week gestation) appropriate size for gestational age neonates in the first 72 h after birth. EXCLUSIONS • preterm or small for gestational age newborns; • term neonates with a diagnosed medical or surgical condition, congenital or otherwise; • babies of diabetic mothers; • neonates with symptomatic hypoglycaemia; • large for gestational age neonates (as significant proportion are of diabetic mothers). TYPES OF INTERVENTION: All interventions that fell within the scope of practice of a midwife/nurse were included: • type (breast or breast milk substitutes), amount and/or timing of feeds, for example, initiation of feeding, and frequency; • regulation of body temperature; • monitoring (including screening) of neonates, including blood or plasma glucose levels and signs and symptoms of hypoglycaemia. Interventions that required initiation by a medical practitioner were excluded from the review. TYPES OF OUTCOME MEASURES Outcomes that were of interest included: • occurrence of hypoglycaemia; • re-establishment and maintenance of blood or plasma glucose levels at or above set threshold (as defined by the particular study); • successful breast-feeding; • developmental outcomes. TYPES OF RESEARCH DESIGNS: The review initially focused on randomised controlled trials reported from 1995 to 2004. Insufficient randomised controlled trials were identified and the review was expanded to include additional cohort and cross-sectional studies for possible inclusion in a narrative summary. SEARCH STRATEGY The major electronic databases, including MEDLINE/PubMed, CINAHL, EMBASE, LILACS, Cochrane Library, etc., were searched using accepted search techniques to identify relevant published and unpublished studies undertaken between 1995 and 2004. Efforts were made to locate any relevant unpublished materials, such as conference papers, research reports and dissertations. Printed journals were hand-searched and reference lists checked for potentially useful research. The year 1995 was selected as the starting point in order to identify any research that had not been included in the World Health Organisation review, which covered literature published up to 1996. The search was not limited to English language studies. ASSESSMENT OF QUALITY: Three primary reviewers conducted the review assisted by a review panel. The review panel was comprised of nine nurses with expertise in neonatal care drawn from senior staff in several metropolitan neonatal units and education programs. Authorship of journal articles was not concealed from the reviewers. Methodological quality of each study that met the inclusion criteria was assessed by two reviewers, using a quality assessment checklist developed for the review. Disagreements between reviewers were resolved through discussion or with the assistance of a third reviewer. DATA EXTRACTION AND ANALYSIS Two reviewers used a data extraction form to independently extract data relating to the study design, setting and participants; study focus and intervention(s); and measurements and outcomes. As only one relevant randomised controlled trial was found, a meta-analysis could not be conducted nor tables constructed to illustrate comparisons between studies. Instead, the findings were summarised by a narrative identifying any relevant findings that emerged from the data. RESULTS Seven studies met the inclusion criteria for the objective of this systematic review. The review provided information on the effectiveness of three categories of intervention - type of feeds, timing of feeds and thermoregulation on two of the outcome measures identified in the review protocol - prevention of hypoglycaemia, and re-establishment and maintenance of blood or plasma glucose levels above the set threshold (as determined by the particular study). There was no evidence available on which to base conclusions for effectiveness of monitoring or developmental outcomes, and insufficient evidence for breast-feeding success. Given that only a narrative review was possible, the findings of this review should be interpreted with caution. The findings suggest that the incidence of hypoglycaemia in healthy, breast-fed term infants of appropriate size for gestational age is uncommon and routine screening of these infants is not indicated. The method and timing of early feeding has little or no influence on the neonatal blood glucose measurement at 1 h in normal term babies. In healthy, breast-fed term infants the initiation and timing of feeds in the first 6 h of life has no significant influence on plasma glucose levels. The colostrum of primiparous mothers provides sufficient nutrition for the infant in the first 24 h after birth, and supplemental feeds or extra water is unnecessary. Skin-to-skin contact appears to provide an optimal environment for fetal to neonatal adaptation after birth and can help to maintain body temperature and adequate blood glucose levels in healthy term newborn infants, as well as providing an ideal opportunity to establish early bonding behaviours. IMPLICATIONS FOR PRACTICE The seven studies analysed in this review confirm the World Health Organisation's first three recommendations for prevention and management of asymptomatic hypoglycaemia, namely: 1 Early and exclusive breast-feeding is safe to meet the nutritional needs of healthy term newborns worldwide. 2 Healthy term newborns that are breast-fed on demand need not have their blood glucose routinely checked and need no supplementary foods or fluids. 3 Healthy term newborns do not develop 'symptomatic' hypoglycaemia as a result of simple underfeeding. If an infant develops signs suggesting hypoglycaemia, look for an underlying condition. Detection and treatment of the cause are as important as correction of the blood glucose level. If there are any concerns that the newborn infant might be hypoglycaemic it should be given another feed. Given the importance of thermoregulation, skin-to-skin contact should be promoted and 'kangaroo care' encouraged in the first 24 h after birth. While it is important to main the infant's body temperature care should be taken to ensure that the child does not become overheated.
Collapse
Affiliation(s)
- Vivien Hewitt
- Curtin University of Technology and The Western Australian Centre for Evidence-based Nursing and Midwifery (a collaborating centre of the Joanna Briggs Institute), Perth, Western Australia, Australia
| | | | | | | |
Collapse
|
8
|
Senniappan S, Shanti B, James C, Hussain K. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. J Inherit Metab Dis 2012; 35:589-601. [PMID: 22231386 DOI: 10.1007/s10545-011-9441-2] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2011] [Revised: 12/06/2011] [Accepted: 12/13/2011] [Indexed: 10/14/2022]
Abstract
Hyperinsulinaemic hypoglycaemia (HH) is due to the unregulated secretion of insulin from pancreatic β-cells. A rapid diagnosis and appropriate management of these patients is essential to prevent the potentially associated complications like epilepsy, cerebral palsy and neurological impairment. The molecular basis of HH involves defects in key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) which regulate insulin secretion. The most severe forms of HH are due to loss of function mutations in ABCC8/KCNJ11 which encode the SUR1 and KIR6.2 components respectively of the pancreatic β-cell K(ATP) channel. At a histological level there are two major forms (diffuse and focal) each with a different genetic aetiology. The diffuse form is inherited in an autosomal recessive (or dominant) manner whereas the focal form is sporadic in inheritance and is localised to a small region of the pancreas. The focal form can now be accurately localised pre-operatively using a specialised positron emission tomography scan with the isotope Fluroine-18L-3, 4-dihydroxyphenyalanine (18F-DOPA-PET). Focal lesionectomy can provide cure from the hypoglycaemia. However the diffuse form is managed medically or by near total pancreatectomy (with high risk of diabetes mellitus). Recent advances in molecular genetics, imaging with 18F-DOPA-PET/CT and novel surgical techniques have changed the clinical approach to patients with HH.
Collapse
Affiliation(s)
- Senthil Senniappan
- Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Trust WC1N 3JH and Institute of Child Health, University College London, London, WC1N 1EH, UK
| | | | | | | |
Collapse
|
9
|
West NJ, Thorpe M. Neonatal hyperinsulinism secondary to maternal intake of high-sugar drinks. BMJ Case Rep 2011; 2011:bcr.03.2011.3990. [PMID: 22689550 DOI: 10.1136/bcr.03.2011.3990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The authors report a macrosomic term male infant who developed refractory hyperinsulinism requiring 20 mg/kg/min intravenous dextrose (usual range 4-6 mg/kg/min) and treatment with diazoxide 10 mg/kg/day. His blood insulin level at 6 h of age was 22.3 mU/l (reference range <5 mU/l) with corresponding laboratory blood glucose of 0.3 mmol/l. There was no detected maternal diabetes but the mother revealed she drank 2 l of 'lucozade energy' a day in the past 3 months of pregnancy. The hyperinsulinism resolved by day 7. Transient neonatal hyperinsulinism is known to be associated with maternal diabetes but has not previously been reported as secondary to high maternal sugar intake. This case highlights that significant hypoglycaemia secondary to transient hyperinsulinism can occur in infants of mothers without identified diabetes.
Collapse
Affiliation(s)
- Nicol Jon West
- Department of Paediatrics, Bristol Children's Hospital, Bristol, UK.
| | | |
Collapse
|
10
|
Birth asphyxia as the major complication in newborns: moving towards improved individual outcomes by prediction, targeted prevention and tailored medical care. EPMA J 2011. [PMID: 23199149 PMCID: PMC3405378 DOI: 10.1007/s13167-011-0087-9] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Perinatal Asphyxia—oxygen deficit at delivery—can lead to severe hypoxic ischaemic organ damage in newborns followed by a fatal outcome or severe life-long pathologies. The severe insults often cause neurodegenerative diseases, mental retardation and epilepsies. The mild insults lead to so-called “minimal brain-damage disorders” such as attention deficits and hyperactivity, but can also be associated with the development of schizophrenia and life-long functional psychotic syndromes. Asphyxia followed by re-oxygenation can potentially lead to development of several neurodegenerative pathologies, diabetes type 2 and cancer. The task of individual prediction, targeted prevention and personalised treatments before a manifestation of the life-long chronic pathologies usually developed by newborns with asphyxic deficits, should be given the extraordinary priority in neonatology and paediatrics. Socio-economical impacts of educational measures and advanced strategies in development of robust diagnostic approaches targeted at effected molecular pathways, biomarker-candidates and potential drug-targets for tailored treatments are reviewed in the paper.
Collapse
|
11
|
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; 92:568-70. [PMID: 17588969 PMCID: PMC2083756 DOI: 10.1136/adc.2006.115543] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
In patients with suspected hyperinsulinaemic hypoglycaemia, blood glucose concentrations should be maintained within the normal range during routine management
Collapse
Affiliation(s)
- Khalid Hussain
- London Centre for Paediatric Endocrinology and Metabolism, Great Ormond Street Hospital for Children NHS Trust, London, UK.
| | | | | | | |
Collapse
|
12
|
Guerrero-Fernández J, González Casado I, Espinoza Colindres L, Gracia Bouthelier R. Hiperinsulinismo congénito. Revisión de 22 casos. An Pediatr (Barc) 2006; 65:22-31. [PMID: 16945287 DOI: 10.1157/13090894] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Congenital hyperinsulinism (CHI) is the most common cause of recurrent episodes of hypoglycemia in early childhood and consists of a group of distinct genetic disorders causing dysregulation of insulin secretion. OBJECTIVE To review the presentation, management and outcome of patients with CHI attended at our hospital. MATERIAL AND METHODS A retrospective review of all patients diagnosed with CHI between 1982 and 2004 was performed. Data were collected on age, gender, clinical presentation, medical and surgical management, and complications. RESULTS Twenty-two patients were identified. Notable features were early symptom onset in 80 %, pancreatectomy in 72 %, and neurological sequels in 28 % (abnormal neurodevelopment in 22 % and epilepsy in 13 %). CONCLUSIONS The presentation, management and outcome in our patients were similar to those in other series, indicating the need for early diagnosis and treatment to avoid neurological sequels.
Collapse
|
13
|
Kurtoglu S, Akcakus M, Keskin M, Ozcan A, Hussain K. Severe hyperinsulinaemic hypoglycaemia in a baby born to a mother taking oral ritodrine therapy for preterm labour. HORMONE RESEARCH 2005; 64:61-3. [PMID: 16103685 DOI: 10.1159/000087471] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2005] [Accepted: 06/10/2005] [Indexed: 11/19/2022]
Abstract
Hyperinsulinism of infancy is a major cause of persistent hypoglycaemia in the newborn period. Transient mild self-limiting hyperinsulinaemia and hypoglycaemia have been described in neonates born to mothers taking ritodrine therapy for premature labour. Ritodrine crosses the placental barrier and enters the fetal circulation readily but the mechanism of how it causes hyperinsulinaemia and hypoglycaemia is unclear. We report the case of severe prolonged hyperinsulinaemic hypoglycamia in a neonate born to a mother taking ritodrine therapy from 16 weeks' gestation for preterm labour. The hyperinsulinaemic hypoglycaemia was managed with oral nifedipine as diazoxide was contraindicated due to fluid overload. Possible mechanisms of ritodrine-induced hypoglycaemia and insulin secretion are discussed.
Collapse
|
14
|
Nursing and midwifery management of hypoglycaemia in healthy term neonates. INT J EVID-BASED HEA 2005. [DOI: 10.1097/01258363-200508000-00001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
15
|
Claudius I, Fluharty C, Boles R. The Emergency Department Approach to Newborn and Childhood Metabolic Crisis. Emerg Med Clin North Am 2005; 23:843-83, x. [PMID: 15982549 DOI: 10.1016/j.emc.2005.03.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
For most emergency medicine physicians, the phrases "newborn workup" and "metabolic disease" are, at best, uncomfortable. This article, however, provides a simple approach to the recognition,evaluation, and treatment of infants with all manners of metabolic issues, including hypoglycemia, inborn errors of metabolism, jaundice, and electrolyte abnormalities. The disorders are grouped based on symptomatology, and have simple guidelines for work-up and management, with an emergency department practitioner perspective in mind.
Collapse
MESH Headings
- Acid-Base Equilibrium
- Adrenal Hyperplasia, Congenital/diagnosis
- Adrenal Hyperplasia, Congenital/metabolism
- Diagnosis, Differential
- Electrolytes/blood
- Emergency Service, Hospital
- Humans
- Hypoglycemia/diagnosis
- Hypoglycemia/drug therapy
- Hypoglycemia/physiopathology
- Infant, Newborn
- Infant, Newborn, Diseases/diagnosis
- Infant, Newborn, Diseases/therapy
- Jaundice, Neonatal/diagnosis
- Jaundice, Neonatal/physiopathology
- Jaundice, Neonatal/therapy
- Metabolism, Inborn Errors/diagnosis
- Metabolism, Inborn Errors/therapy
Collapse
Affiliation(s)
- Ilene Claudius
- Department of Emergency and Transport Medicine, Children's Hospital Los Angeles, 4650 Sunset Boulevard, MS113, Los Angeles, CA 90027, USA
| | | | | |
Collapse
|
16
|
Abstract
Assessment of neonatal glycaemic status requires accurate and reliable measurement of blood glucose concentrations. Most point-of-care technologies are, however, unsuitable for use in neonates. Although the definition of hypoglycaemia remains elusive, current knowledge allows adoption of pragmatic threshold blood glucose concentrations when clinical intervention should be considered. The vast majority of instances of neonatal hypoglycaemia are due to problems with the normal processes of metabolic adaptation after birth, and strategies to enhance the normal adaptive processes should help prevent such episodes. Further investigations and specific interventions should be considered when hypoglycaemia is of unusual severity or occurs in an otherwise low-risk infant.
Collapse
Affiliation(s)
- Sanjeev Deshpande
- Royal Shrewsbury Hospital, Mytton Oak Road, Shrewsbury, SY2 6SP, UK.
| | | |
Collapse
|
17
|
Hewitt V, Watts R, Robertson J, Haddow G. Nursing and midwifery management of hypoglycaemia in healthy term neonates. ACTA ACUST UNITED AC 2005. [DOI: 10.11124/jbisrir-2005-364] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
|
18
|
Hewitt V, Watts R, Robertson J, Haddow G. Nursing and midwifery management of hypoglycaemia in healthy term neonates. ACTA ACUST UNITED AC 2005; 3:1-63. [PMID: 27819960 DOI: 10.11124/01938924-200503070-00001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
OBJECTIVES The primary objective of this review was to determine the best available evidence for maintenance of euglycaemia in healthy term neonates, and the management of asymptomatic hypoglycaemia in otherwise healthy term neonates. INCLUSION CRITERIA The review included any relevant published or unpublished studies undertaken between 1995 and 2004. Studies that focus on the diagnostic accuracy of point-of-care devices for blood glucose screening and/or monitoring in the neonate were initially included as a subgroup of this review. However, the technical nature and complexity of the statistical information published in diagnostic studies retrieved during the literature search stage, as well as the considerable volume of published research in this area, suggested that it would be more feasible to analyse diagnostic studies in a separate systematic review.The review focused on studies that included healthy term (37- to 42-week gestation) appropriate size for gestational age neonates in the first 72 h after birth.All interventions that fell within the scope of practice of a midwife/nurse were included:Interventions that required initiation by a medical practitioner were excluded from the review.Outcomes that were of interest included:The review initially focused on randomised controlled trials reported from 1995 to 2004. Insufficient randomised controlled trials were identified and the review was expanded to include additional cohort and cross-sectional studies for possible inclusion in a narrative summary. SEARCH STRATEGY The major electronic databases, including MEDLINE/PubMed, CINAHL, EMBASE, LILACS, Cochrane Library, etc., were searched using accepted search techniques to identify relevant published and unpublished studies undertaken between 1995 and 2004. Efforts were made to locate any relevant unpublished materials, such as conference papers, research reports and dissertations. Printed journals were hand-searched and reference lists checked for potentially useful research. The year 1995 was selected as the starting point in order to identify any research that had not been included in the World Health Organisation review, which covered literature published up to 1996. The search was not limited to English language studies. ASSESSMENT OF QUALITY Three primary reviewers conducted the review assisted by a review panel. The review panel was comprised of nine nurses with expertise in neonatal care drawn from senior staff in several metropolitan neonatal units and education programs. Authorship of journal articles was not concealed from the reviewers. Methodological quality of each study that met the inclusion criteria was assessed by two reviewers, using a quality assessment checklist developed for the review. Disagreements between reviewers were resolved through discussion or with the assistance of a third reviewer. DATA EXTRACTION AND ANALYSIS Two reviewers used a data extraction form to independently extract data relating to the study design, setting and participants; study focus and intervention(s); and measurements and outcomes.As only one relevant randomised controlled trial was found, a meta-analysis could not be conducted nor tables constructed to illustrate comparisons between studies. Instead, the findings were summarised by a narrative identifying any relevant findings that emerged from the data. RESULTS Seven studies met the inclusion criteria for the objective of this systematic review. The review provided information on the effectiveness of three categories of intervention - type of feeds, timing of feeds and thermoregulation on two of the outcome measures identified in the review protocol - prevention of hypoglycaemia, and re-establishment and maintenance of blood or plasma glucose levels above the set threshold (as determined by the particular study). There was no evidence available on which to base conclusions for effectiveness of monitoring or developmental outcomes, and insufficient evidence for breast-feeding success.Given that only a narrative review was possible, the findings of this review should be interpreted with caution. The findings suggest that the incidence of hypoglycaemia in healthy, breast-fed term infants of appropriate size for gestational age is uncommon and routine screening of these infants is not indicated. The method and timing of early feeding has little or no influence on the neonatal blood glucose measurement at 1 h in normal term babies. In healthy, breast-fed term infants the initiation and timing of feeds in the first 6 h of life has no significant influence on plasma glucose levels. The colostrum of primiparous mothers provides sufficient nutrition for the infant in the first 24 h after birth, and supplemental feeds or extra water is unnecessary.Skin-to-skin contact appears to provide an optimal environment for fetal to neonatal adaptation after birth and can help to maintain body temperature and adequate blood glucose levels in healthy term newborn infants, as well as providing an ideal opportunity to establish early bonding behaviours. IMPLICATIONS FOR PRACTICE The seven studies analysed in this review confirm the World Health Organisation's first three recommendations for prevention and management of asymptomatic hypoglycaemia, namely:1 Early and exclusive breast-feeding is safe to meet the nutritional needs of healthy term newborns worldwide.2 Healthy term newborns that are breast-fed on demand need not have their blood glucose routinely checked and need no supplementary foods or fluids.3 Healthy term newborns do not develop 'symptomatic' hypoglycaemia as a result of simple underfeeding. If an infant develops signs suggesting hypoglycaemia, look for an underlying condition. Detection and treatment of the cause are as important as correction of the blood glucose level.If there are any concerns that the newborn infant might be hypoglycaemic it should be given another feed. Given the importance of thermoregulation, skin-to-skin contact should be promoted and 'kangaroo care' encouraged in the first 24 h after birth. While it is important to main the infant's body temperature care should be taken to ensure that the child does not become overheated.
Collapse
Affiliation(s)
- Vivien Hewitt
- 1Curtin University of Technology and 2The Western Australian Centre for Evidence-based Nursing and Midwifery (a collaborating centre of the Joanna Briggs Institute), Perth, Western Australia, Australia
| | | | | | | |
Collapse
|
19
|
Abstract
Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous entity and causes severe hypoglycemia in neonates and infants. The clinical heterogeneity is manifested by severity ranging from extremely severe, life-threatening disease to very mild clinical symptoms, which may even be difficult to identify. Furthermore, clinical responsiveness to medical and surgical management is extremely variable. Recent discoveries have begun to clarify the molecular etiology of this disease in about 50% of cases. Mutations in five different genes have been identified in patients with this clinical syndrome. Most cases are caused by mutations in the genes ABCC8 and KCNJ11 coding for either of the two subunits of the beta-cell KATP channel (SUR1 and Kir6.2). Recessive mutations of the beta-cell K(ATP) channel genes cause diffuse HI, whereas loss of heterozygosity together with inheritance of a paternal mutation causes focal adenomatous HI. In other cases, CHI is caused by mutations in genes coding for the beta-cell enzymes glucokinase (GK), glutamate dehydrogenase (GDH), and SCHAD. However, for as many as 50% of the cases, no genetic etiology has yet been determined. The study of the genetics of this disease has provided important new information regarding beta-cell physiology.
Collapse
|