BACKGROUND Diazoxide is the sole approved drug for congenital hyperinsulinism;however,diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse e...BACKGROUND Diazoxide is the sole approved drug for congenital hyperinsulinism;however,diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse effects.This report aims to highlight a seldom-considered rare side effect of diazoxide.We believe that this brief report is of general interest to World Journal of Clinical Pediatric readership and increase the physicians’awareness of the guideline importance.Moreover,it underlines the importance of stopping immediately the drug if suspected side effects.CASE SUMMARY The manuscript describes a patient diagnosed with congenital hyperinsulinism(CHI)treated with diazoxide not overlapping with diuretic.He resulted in sudden respiratory distress and therefore was transferred to the Neonatal Intensive Care Unit.The cardiological evaluation showed pericardial effusion and left ventricular myocardial hypertrophy,absent before.In suspicion of an iatrogenic effect of diazoxide it was progressively reduced until stop while introducing diuretic treatment,with resolution of symptoms.Once clinically stabilized,an 18 fluoro-diydroxy-phenylalanine positron emission tomography/computed tomography(PET/CT)was performed to differentiate between a focal or diffuse form of CHI.The PET/CT highlighted the presence of a single focal accumulation of the tracer located in the pancreatic tail,consistent with a focal form of hyperin-sulinism.At the age of four months,the patient underwent a distal pancreatectomy with histological confirmation of a focal form of nesidioblastosis,resulting in a curative operation.CONCLUSION Diuretic administration and vigilant monitoring of diazoxide therapy are crucial to prevent and promptly identify potentially life-threatening adverse effects.展开更多
Congenital hyperinsulinism(CHI) is a rare but complex heterogeneous disorder caused by unregulated secre-tion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift di...Congenital hyperinsulinism(CHI) is a rare but complex heterogeneous disorder caused by unregulated secre-tion 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 neurodevel-opmental 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 de-velopment of iatrogenic diabetes mellitus and pancre-atic exocrine insufficiency. However patients with focaldisease only require a limited pancreatectomy to re-move 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-hydroxy-phenylalanine positron emission tomography(18F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and locali-sation 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.展开更多
Importance: Octreotide is an off-label medicine for congenital hyperinsulinism (CHI), but is currently widely used for treatment of patients with CHI. Thus far, variable efficacy and adverse effects have been reported...Importance: Octreotide is an off-label medicine for congenital hyperinsulinism (CHI), but is currently widely used for treatment of patients with CHI. Thus far, variable efficacy and adverse effects have been reported for octreotide.Objective: The present study evaluated the efficacy and safety of a subcutaneous octreotide injection for treatment of diazoxide-unresponsive CHI in China.Methods: This study was a retrospective review of children with diazoxide-unresponsive CHI who were treated with a subcutaneous octreotide injection. The efficacy and side effects of the treatment were assessed.Results: Twenty-five Chinese children (15 boys) were involved in the study. Their median age at diagnosis was 8 weeks (range, 1-24 weeks) and median age at the final follow-up was 1.8 years (range, 0.3-3.3 years). Octreotide therapy effectively increased blood glucose levels in all patients. The intravenous glucose infusion rate was reduced in all patients. Twenty-one patients gradually discontinued the intravenous glucose infusion while receiving octreotide combined with frequent carbohydrate/glucose-rich feeding. Among patients with a monoallelic ATP-sensitive potassium (KATP) channel mutation, 50.0% showed gradual remission during follow up, indicating that the octreotide treatment may be a feasible alternative to surgery, especially for patients with monoallelic KATP-channel mutations. Transient elevation of liver enzymes occurred in 20.0% of patients, while asymptomatic gallbladder pathology occurred in one patient. The growth rates of these patients were normal (height standard deviation score was 0.3 ± 1.5 at the final follow-up).Interpretation: Octreotide was a well-tolerated, effective therapy for most children with diazoxide-unresponsive CHI.展开更多
BACKGROUND Neonatal hyperinsulinism can result from perinatal stress,genetic disorders,or syndromes,which can lead to persistent or intractable hypoglycemia in newborns.Mutations in the ABCC8 gene result in abnormal f...BACKGROUND Neonatal hyperinsulinism can result from perinatal stress,genetic disorders,or syndromes,which can lead to persistent or intractable hypoglycemia in newborns.Mutations in the ABCC8 gene result in abnormal functioning of potassium channel proteins in pancreaticβ-cells,leading to an overproduction of insulin and congenital hyperinsulinemia.CASE SUMMARY We report a case of a high-birth-weight infant with postnatal hypoglycemia and hyperinsulinemia,whose mother had pregestational diabetes mellitus with poor glycemic control and whose sister had a similar history at birth.Whole-exome sequencing revealed a new mutation in the ABCC8 gene in exon 8(c.1257T>G),which also occurred in his sister and mother;thus,the patient was diagnosed with neonatal hyperinsulinism with an ABCC8 mutation.With oral diazoxide treatment,the child’s blood glucose returned to normal,and the pediatrician gradually discontinued treatment because of the child’s good growth and development.CONCLUSION We report a new mutation locus in the ABCC8 gene.This mutation locus warrants attention for genetic disorders and long-term prognoses of hypoglycemic children.展开更多
文摘BACKGROUND Diazoxide is the sole approved drug for congenital hyperinsulinism;however,diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse effects.This report aims to highlight a seldom-considered rare side effect of diazoxide.We believe that this brief report is of general interest to World Journal of Clinical Pediatric readership and increase the physicians’awareness of the guideline importance.Moreover,it underlines the importance of stopping immediately the drug if suspected side effects.CASE SUMMARY The manuscript describes a patient diagnosed with congenital hyperinsulinism(CHI)treated with diazoxide not overlapping with diuretic.He resulted in sudden respiratory distress and therefore was transferred to the Neonatal Intensive Care Unit.The cardiological evaluation showed pericardial effusion and left ventricular myocardial hypertrophy,absent before.In suspicion of an iatrogenic effect of diazoxide it was progressively reduced until stop while introducing diuretic treatment,with resolution of symptoms.Once clinically stabilized,an 18 fluoro-diydroxy-phenylalanine positron emission tomography/computed tomography(PET/CT)was performed to differentiate between a focal or diffuse form of CHI.The PET/CT highlighted the presence of a single focal accumulation of the tracer located in the pancreatic tail,consistent with a focal form of hyperin-sulinism.At the age of four months,the patient underwent a distal pancreatectomy with histological confirmation of a focal form of nesidioblastosis,resulting in a curative operation.CONCLUSION Diuretic administration and vigilant monitoring of diazoxide therapy are crucial to prevent and promptly identify potentially life-threatening adverse effects.
文摘Congenital hyperinsulinism(CHI) is a rare but complex heterogeneous disorder caused by unregulated secre-tion 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 neurodevel-opmental 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 de-velopment of iatrogenic diabetes mellitus and pancre-atic exocrine insufficiency. However patients with focaldisease only require a limited pancreatectomy to re-move 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-hydroxy-phenylalanine positron emission tomography(18F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and locali-sation 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.
基金The study was funded by National Key Research and Development Program of China(2016YFC1305304)Beijing Children's Hospital Young Investigator Program(No.BCHYIPA-2016-06)Beijing Municipal Administration of Hospital Clinical Medicine Development of Special Funding Support(No.ZYLX201821).
文摘Importance: Octreotide is an off-label medicine for congenital hyperinsulinism (CHI), but is currently widely used for treatment of patients with CHI. Thus far, variable efficacy and adverse effects have been reported for octreotide.Objective: The present study evaluated the efficacy and safety of a subcutaneous octreotide injection for treatment of diazoxide-unresponsive CHI in China.Methods: This study was a retrospective review of children with diazoxide-unresponsive CHI who were treated with a subcutaneous octreotide injection. The efficacy and side effects of the treatment were assessed.Results: Twenty-five Chinese children (15 boys) were involved in the study. Their median age at diagnosis was 8 weeks (range, 1-24 weeks) and median age at the final follow-up was 1.8 years (range, 0.3-3.3 years). Octreotide therapy effectively increased blood glucose levels in all patients. The intravenous glucose infusion rate was reduced in all patients. Twenty-one patients gradually discontinued the intravenous glucose infusion while receiving octreotide combined with frequent carbohydrate/glucose-rich feeding. Among patients with a monoallelic ATP-sensitive potassium (KATP) channel mutation, 50.0% showed gradual remission during follow up, indicating that the octreotide treatment may be a feasible alternative to surgery, especially for patients with monoallelic KATP-channel mutations. Transient elevation of liver enzymes occurred in 20.0% of patients, while asymptomatic gallbladder pathology occurred in one patient. The growth rates of these patients were normal (height standard deviation score was 0.3 ± 1.5 at the final follow-up).Interpretation: Octreotide was a well-tolerated, effective therapy for most children with diazoxide-unresponsive CHI.
文摘BACKGROUND Neonatal hyperinsulinism can result from perinatal stress,genetic disorders,or syndromes,which can lead to persistent or intractable hypoglycemia in newborns.Mutations in the ABCC8 gene result in abnormal functioning of potassium channel proteins in pancreaticβ-cells,leading to an overproduction of insulin and congenital hyperinsulinemia.CASE SUMMARY We report a case of a high-birth-weight infant with postnatal hypoglycemia and hyperinsulinemia,whose mother had pregestational diabetes mellitus with poor glycemic control and whose sister had a similar history at birth.Whole-exome sequencing revealed a new mutation in the ABCC8 gene in exon 8(c.1257T>G),which also occurred in his sister and mother;thus,the patient was diagnosed with neonatal hyperinsulinism with an ABCC8 mutation.With oral diazoxide treatment,the child’s blood glucose returned to normal,and the pediatrician gradually discontinued treatment because of the child’s good growth and development.CONCLUSION We report a new mutation locus in the ABCC8 gene.This mutation locus warrants attention for genetic disorders and long-term prognoses of hypoglycemic children.
