Pancreatic endocrine and exocrine function in children following near-total pancreatectomy for diffuse congenital hyperinsulinism.
BACKGROUND
Congenital hyperinsulinism (CHI), the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency.


METHODS
International referral centre for the management of CHI.


METHODS
Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012.


METHODS
Near-total pancreatectomy.


METHODS
Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1) pancreatic exocrine insufficiency.


RESULTS
Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72%) had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1<100 µg/g). Clinical exocrine insufficiency was observed in 22 (49%) patients. No statistically significant difference in weight and height standard deviation score (SDS) was found between untreated subclinical pancreatic exocrine insufficiency patients and treated clinical pancreatic exocrine insufficiency patients.


CONCLUSIONS
The outcome of diffuse CHI patients after near-total pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation.
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Institute of Child Health, University College London, London, United Kingdom.
Ved Bhushan
VB
Arya
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Institute of Child Health, University College London, London, United Kingdom.
Senthil
S
Senniappan
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Institute of Child Health, University College London, London, United Kingdom; Departments of Paediatric Endocrinology, Ankara Pediatric Hematology and Oncology Training Hospital, Ankara, Turkey.
Huseyin
H
Demirbilek
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
Syeda
S
Alam
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom.
Sarah E
SE
Flanagan
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom.
Sian
S
Ellard
Department of Paediatric Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Institute of Child Health, University College London, London, United Kingdom.
Khalid
K
Hussain
D000886:Anthropometry; D001483:Base Sequence; D002648:Child; D044903:Congenital Hyperinsulinism / Q000503:physiopathology* / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D010188:Exocrine Pancreatic Insufficiency / Q000473:pathology; D006801:Humans; D007003:Hypoglycemia / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008131:London; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D010179:Pancreas / Q000503:physiopathology*; D010180:Pancreatectomy / Q000009:adverse effects*; D010196:Pancreatic Elastase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D017422:Sequence Analysis, DNA; D064233:Sulfonylurea Receptors / Q000235:genetics; D000099161:Kcnj11 Channel
D010196:Pancreatic Elastase; D024661:Potassium Channels, Inwardly Rectifying; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human