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
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
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
We review the case of a 74-year-old patient with ad-vanced colon cancer who suffered recurrent bouts of hypoglycemia. A state of inappropriate, non-suppressed hyperinsulinism in the presence of severe hypoglycemia was...We review the case of a 74-year-old patient with ad-vanced colon cancer who suffered recurrent bouts of hypoglycemia. A state of inappropriate, non-suppressed hyperinsulinism in the presence of severe hypoglycemia was diagnosed. We finally discuss the known mecha-nisms behind fasting hypoglycemia in patients with ad-vanced cancer, the diagnosis, and possible treatments of this rare paraneoplastic endocrine complication.展开更多
Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological,cellular,and clinical levels.Rheumatologists have marked them as ...Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological,cellular,and clinical levels.Rheumatologists have marked them as two entirely distinct arthropathies.Given recent dis-coveries in disease initiation and progression,potential mechanisms,cellular signaling path-ways,and ongoing clinical therapeutics,there are now more opportunities for discovering osteoarthritis drugs.This review summarized the osteoarthritis and psoriasis arthritis signaling pathways,crosstalk between BMP,WNT,TGF-β,VEGF,TLR,and FGF signaling pathways,bio-markers,and anatomical pathologies.Through bench research,we demonstrated that regen-erative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses,multiple signaling blockers,and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation.Furthermore,we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.展开更多
Diabetes mellitus and associated chronic hyperglycemia enhance the risk of acute ischemic stroke and lead to worsened clinical outcome and increased mortality. However, post-stroke hyperglycemia is also present in a n...Diabetes mellitus and associated chronic hyperglycemia enhance the risk of acute ischemic stroke and lead to worsened clinical outcome and increased mortality. However, post-stroke hyperglycemia is also present in a number of non-diabetic patients after acute ischemic stroke, presumably as a stress response. The aim of this review is to summarize the main effects of hyperglycemia when associated to ischemic injury in acute stroke patients, highlighting the clinical and neurological outcomes in these conditions and after the administration of the currently approved pharmacological treatment, i.e. insulin. The disappointing results of the clinical trials on insulin(including the hypoglycemic events) demand a change of strategy based on more focused therapies. Starting from the comprehensive evaluation of the physiopathological alterations occurring in the ischemic brain during hyperglycemic conditions, the effects of various classes of glucose-lowering drugs are reviewed, such as glucose-like peptide-1 receptor agonists, DPP-4 inhibitors and sodium glucose cotransporter 2 inhibitors, in the perspective of overcoming the up-to-date limitations and of evaluating the effectiveness of new potential therapeutic strategies.展开更多
The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and...The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors(such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase(GDH) and HADH gene, encoding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism.展开更多
发育性髋关节发育不良(developmental dysplasia of the hip,DDH)是常见的儿童肢体畸形,早期筛查和诊断非常重要,延误治疗或治疗不当将导致严重后果。股骨头缺血性坏死(avascular necrosis,AVN)是DDH闭合复位后严重且常见的并发症,如何...发育性髋关节发育不良(developmental dysplasia of the hip,DDH)是常见的儿童肢体畸形,早期筛查和诊断非常重要,延误治疗或治疗不当将导致严重后果。股骨头缺血性坏死(avascular necrosis,AVN)是DDH闭合复位后严重且常见的并发症,如何预防及避免AVN的发生一直困扰着小儿骨科医师。闭合复位前骨化核的存在似乎有助于降低AVN发生率,避免AVN的发生与DDH早诊断、早治疗关系密切。本文就骨化核与DDH闭合复位后AVN相关性的研究进展进行综述。展开更多
46,XY性发育异常(disorders of sex development,DSD)是一种遗传学性别、表型性别和性腺性别不一致的先天性疾病,确诊该病的关键是基因检测。回顾分析1例46,XY DSD患者,患者社会性别为女性,因查体发现性腺发育异常就诊。患者46,XY DSD...46,XY性发育异常(disorders of sex development,DSD)是一种遗传学性别、表型性别和性腺性别不一致的先天性疾病,确诊该病的关键是基因检测。回顾分析1例46,XY DSD患者,患者社会性别为女性,因查体发现性腺发育异常就诊。患者46,XY DSD合并肥胖及高胰岛素血症,致病基因为类固醇生成因子-1(steroidogenic factor 1,SF-1,又称NR5A1),突变位点为c.1095_1096insTCGG(p.Q366Sfs*22),对该基因进行遗传学分析,该位点所致的基因突变可能与肥胖及糖尿病相关。行腹腔镜双侧隐睾切除术+外阴整形术+阴蒂切除术,维持患者女性社会性别。从遗传学角度检测病因可为46,XY DSD的临床诊治提供指导及依据。展开更多
Bland-White-Garland syndrome or ALCAPA is an abnormality of birth of the left coronary artery from the pulmonary artery. It is a diagnostic and therapeutic emergency because it is a curable cause of hypokinetic dilate...Bland-White-Garland syndrome or ALCAPA is an abnormality of birth of the left coronary artery from the pulmonary artery. It is a diagnostic and therapeutic emergency because it is a curable cause of hypokinetic dilated heart disease in infants. We report through this clinical case, the fourth case of infantile ALCAPA diagnosed in Senegal in a 7-month-old infant. The symptomatology began around the age of 2 months, with a grumpy state associated with more marked crying and moaning during feedings and bowel movements. The mother reported hospitalization for a severe lung infection when she was 6 months old. The examination noted an infant in poor general condition, retarded growth and weight, and a 3/6th holosystolic murmur at the apex. Troponinemia was positive at 43.90 ng/L. The electrocardiogram showed Q waves on the lower side, a sub endocardial lesion on the upper side and a ST segment elevation in aVR. Doppler echocardiography showed dilated cardiomyopathy with a mean alteration of systolic function of the left ventricle at 37%, a mean mitral insufficiency and a strong suspicion of a birth anomaly of the left coronary artery. The CT scan confirmed the diagnosis of ALCAPA. Surgicalreimplantation of the left coronary artery at the aortic level was performed at 10 months of life with a favourable outcome at D50 postoperative.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.
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.
文摘We review the case of a 74-year-old patient with ad-vanced colon cancer who suffered recurrent bouts of hypoglycemia. A state of inappropriate, non-suppressed hyperinsulinism in the presence of severe hypoglycemia was diagnosed. We finally discuss the known mecha-nisms behind fasting hypoglycemia in patients with ad-vanced cancer, the diagnosis, and possible treatments of this rare paraneoplastic endocrine complication.
文摘Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological,cellular,and clinical levels.Rheumatologists have marked them as two entirely distinct arthropathies.Given recent dis-coveries in disease initiation and progression,potential mechanisms,cellular signaling path-ways,and ongoing clinical therapeutics,there are now more opportunities for discovering osteoarthritis drugs.This review summarized the osteoarthritis and psoriasis arthritis signaling pathways,crosstalk between BMP,WNT,TGF-β,VEGF,TLR,and FGF signaling pathways,bio-markers,and anatomical pathologies.Through bench research,we demonstrated that regen-erative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses,multiple signaling blockers,and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation.Furthermore,we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.
基金supported by a grant from Catholic Universitary Center(Centro Universitario Cattolico)-Conferenza Episcopale Italiana,Rome,Italy(to FF)。
文摘Diabetes mellitus and associated chronic hyperglycemia enhance the risk of acute ischemic stroke and lead to worsened clinical outcome and increased mortality. However, post-stroke hyperglycemia is also present in a number of non-diabetic patients after acute ischemic stroke, presumably as a stress response. The aim of this review is to summarize the main effects of hyperglycemia when associated to ischemic injury in acute stroke patients, highlighting the clinical and neurological outcomes in these conditions and after the administration of the currently approved pharmacological treatment, i.e. insulin. The disappointing results of the clinical trials on insulin(including the hypoglycemic events) demand a change of strategy based on more focused therapies. Starting from the comprehensive evaluation of the physiopathological alterations occurring in the ischemic brain during hyperglycemic conditions, the effects of various classes of glucose-lowering drugs are reviewed, such as glucose-like peptide-1 receptor agonists, DPP-4 inhibitors and sodium glucose cotransporter 2 inhibitors, in the perspective of overcoming the up-to-date limitations and of evaluating the effectiveness of new potential therapeutic strategies.
文摘The interplay between glucose metabolism and that of the two other primary nutrient classes, amino acids and fatty acids is critical for regulated insulin secretion. Mitochondrial metabolism of glucose, amino acid and fatty acids generates metabolic coupling factors(such as ATP, NADPH, glutamate, long chain acyl-CoA and diacylglycerol) which trigger insulin secretion. The observation of protein induced hypoglycaemia in patients with mutations in GLUD1 gene, encoding the enzyme glutamate dehydrogenase(GDH) and HADH gene, encoding for the enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase has provided new mechanistic insights into the regulation of insulin secretion by amino acid and fatty acid metabolism. Metabolic signals arising from amino acid and fatty acid metabolism converge on the enzyme GDH which integrates both signals from both pathways and controls insulin secretion. Hence GDH seems to play a pivotal role in regulating both amino acid and fatty acid metabolism.
文摘发育性髋关节发育不良(developmental dysplasia of the hip,DDH)是常见的儿童肢体畸形,早期筛查和诊断非常重要,延误治疗或治疗不当将导致严重后果。股骨头缺血性坏死(avascular necrosis,AVN)是DDH闭合复位后严重且常见的并发症,如何预防及避免AVN的发生一直困扰着小儿骨科医师。闭合复位前骨化核的存在似乎有助于降低AVN发生率,避免AVN的发生与DDH早诊断、早治疗关系密切。本文就骨化核与DDH闭合复位后AVN相关性的研究进展进行综述。
文摘46,XY性发育异常(disorders of sex development,DSD)是一种遗传学性别、表型性别和性腺性别不一致的先天性疾病,确诊该病的关键是基因检测。回顾分析1例46,XY DSD患者,患者社会性别为女性,因查体发现性腺发育异常就诊。患者46,XY DSD合并肥胖及高胰岛素血症,致病基因为类固醇生成因子-1(steroidogenic factor 1,SF-1,又称NR5A1),突变位点为c.1095_1096insTCGG(p.Q366Sfs*22),对该基因进行遗传学分析,该位点所致的基因突变可能与肥胖及糖尿病相关。行腹腔镜双侧隐睾切除术+外阴整形术+阴蒂切除术,维持患者女性社会性别。从遗传学角度检测病因可为46,XY DSD的临床诊治提供指导及依据。
文摘Bland-White-Garland syndrome or ALCAPA is an abnormality of birth of the left coronary artery from the pulmonary artery. It is a diagnostic and therapeutic emergency because it is a curable cause of hypokinetic dilated heart disease in infants. We report through this clinical case, the fourth case of infantile ALCAPA diagnosed in Senegal in a 7-month-old infant. The symptomatology began around the age of 2 months, with a grumpy state associated with more marked crying and moaning during feedings and bowel movements. The mother reported hospitalization for a severe lung infection when she was 6 months old. The examination noted an infant in poor general condition, retarded growth and weight, and a 3/6th holosystolic murmur at the apex. Troponinemia was positive at 43.90 ng/L. The electrocardiogram showed Q waves on the lower side, a sub endocardial lesion on the upper side and a ST segment elevation in aVR. Doppler echocardiography showed dilated cardiomyopathy with a mean alteration of systolic function of the left ventricle at 37%, a mean mitral insufficiency and a strong suspicion of a birth anomaly of the left coronary artery. The CT scan confirmed the diagnosis of ALCAPA. Surgicalreimplantation of the left coronary artery at the aortic level was performed at 10 months of life with a favourable outcome at D50 postoperative.
