A mild case of nesidioblastosis with diagnostic and therapeutic difficulty

A female infant with nesidioblastosis who showed mild clinical symptoms is reported. In this patient, insulin levels and insulin to glucose ratios (IRI/G) were often normal. Regular milk feedings supplemented with continuous glucose infusion (0.7-2 mg/kg per min) or oral glucose feedings (4.5 mg/kg per min) prevented hypoglycemia. As leucine-sensitivity was diagnosed at 2 months of age, she was started on diazoxide. This was, however, ineffective, and adverse effects appeared. Subtotal pancreatectomy (95%) was therefore attempted at 5 months of age, and persistent normoglycemia as well as normal growth and development followed up to 3 years after the operation. The pancreas showed characteristic signs of nesidioblastosis. The above clinical observation suggests that a patient with nesidioblastosis whose blood glucose level is easily controllable may develop an unexpected episode of hypoglycemia in the presence of a leucine sensitivity. In such a patient, diazoxide or, when it is of no avail, surgical intervention should promptly be instituted to prevent possible neurologic sequelae induced by hypoglycemia.     

Genetics of congenital hyperinsulinism

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.     

Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.     

高胰岛素血症伴高氨血症综合征1例报告并文献复习

目的探讨GLUD1基因变异所致高胰岛素血症伴高氨血症综合征临床表现和致病基因特点。方法回顾分析1例高胰岛素血症伴高氨血症综合征患儿的临床资料,并复习相关文献。结果女性患儿,1岁9个月起病,反复出现血糖偏低2年余,并惊厥发作3次,给予升血糖、止惊对症处理后可缓解;伴血胰岛素、血氨水平升高,诊断为高胰岛素血症伴高氨血症综合征。高通量测序发现患儿GLUD1基因存在错义变异c.965GA,p.Arg322His(杂合),其父母该位点均为正常基因型,为新生突变。结论基因检测有助于明确高胰岛素血症伴高氨血症综合征诊断。     

A case report of methadone-associated hypoglycemia in an 11-month-old male

Background: Methadone is a synthetic μ-opioid receptor agonist that is used in the management of pain, neonatal abstinence withdrawal syndrome, and opioid dependence. Overdose can cause miosis, respiratory depression, and central nervous system depression. Rarely, hypoglycemia has been reported. We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure.

Case details: The patient was a previously healthy 11-month-old male who presented in respiratory failure. He was intubated and transferred to a large tertiary care center where his physical exam was notable for miosis. His labs were notable for a blood glucose of 17?mg/dL, an elevated insulin level, and suppressed serum beta-hydroxybutyrate. The patient was given a dextrose bolus with improvement in blood glucose. Administration of IV naloxone improved his miosis and mental status. A quantitative methadone level was sent upon arrival and was 123?ng/mL. Testing for ethanol, salicylates, sulfonylureas, and metabolic causes of hypoglycemia was negative. A fasting study showed euglycemia with suppression of insulin and appropriate ketosis.

Case discussion: We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure. Alternative explanations for hypoketotic hypoglycemia were rule out. Methadone-induced hypoglycemia has been reported in cancer patients receiving methadone for pain, but a mechanism has not been identified. Based on this case, we believe that the patient’s hypoglycemia was the result of methadone-induced insulin secretion.

Conclusions: This case proposes that hyperinsulinism is the mechanism responsible for methadone-associated hypoglycemia. Methadone exposure should be included in the differential diagnosis of new onset hypoglycemia.     

Effect of high fat vs. high carbohydrate feeding on the development of obesity in weanling ob/ob mice

Summary Mice with hereditary obesity (ob/ob) were fed isocaloric, isoprotein diets with varying proportions of carbohydrate-to-fat from the time of weaning to 18 weeks of age. Body weight, plasma glucose, and plasma insulin were determined at frequent intervals; body lipid and pancreatic insulin were determined at termination. Obesity developed when only carbohydrate was provided as caloric source (and in the presence of essential fatty acid deficiency), but obesity was greatly enhanced when 5% fat was added. Obesity also developed in the absence of dietary carbohydrate, even though hyperinsulinism was significantly reduced by this regimen. It is concluded that 1) both enhanced storage of dietary fat and lipogenesis contribute to obesity, the former more so than the latter; 2) the degree of hyperinsulinism does not determine the degree of obesity; 3) the development of hyperinsulinism does not require stimulation by exogenous oral carbohydrate.     

Hypoglycemia Worsened by Glucose Administration: A Case of Hypoglycemia Years After Gastric Surgery

BackgroundNoninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a rare syndrome characterized by postprandial hypoglycemia with neuroglycopenic symptoms occurring 1 to 3 h after a meal. Diagnosis can be elusive, as the vast majority of patients have normal fasting blood glucose levels, and onset of hypoglycemic episodes can be a late complication of gastric surgery.Case ReportWe report the case of a 45-year-old woman presenting to the Emergency Department (ED) with new-onset seizures and hypoglycemia worsened by glucose administration. Surgical history is pertinent for a Roux-en-Y gastric bypass approximately 10 years prior to presentation.Why Should an Emergency Physician Be Aware of This?Although rare, it is important for emergency physicians to be vigilant of this disease process as a traditional treatment approach for hypoglycemia may be detrimental. Although cases of NIPHS have been documented in literature, its presence in emergency medicine-specific literature is seemingly nonexistent. Noninvasive imaging techniques will be normal, and diagnosis is dependent on awareness of this disease entity coupled with a detailed history.     

18F-L-DOPA PET/CT显像诊断先天性高胰岛素血症的研究进展

先天性高胰岛素血症（CHI）是由于胰腺β细胞分泌过多的胰岛素导致顽固性的低血糖及与血糖水平不相称的相对高胰岛素血症。CHI的治疗方法包括内科治疗和外科手术治疗,对于内科治疗无效或效果不佳的患者常需要外科手术治疗。CHI主要分为局灶型和弥漫型,局灶型CHI可通过外科手术切除病灶而治愈,弥漫型CHI需进行胰腺次全切除术治疗。因此,手术治疗前明确病理类型至关重要。CT、MRI及超声等影像学检查对于鉴别局灶型与弥漫型CHI具有一定的局限性,而18F-左旋多巴PET/CT显像具有一定优势。笔者对18F-左旋多巴PET/CT显像诊断CHI进行了综述,对临床实践具有一定的指导意义。