婴幼儿持续高胰岛素血症性低血糖症的分子病因

婴幼儿持续高胰岛索血症性低血糖症是婴幼儿持续性低血糖症最常见病因之一。近年来，婴幼儿持续高胰岛素血症性低血糖症的分子发病机制研究有了显著的进展。根据不同的受累基因，可将婴幼儿持续高胰岛素血症性低血糖症大致分为5型，但仍有约半数患者仍未发现致病基因。     

婴儿持续性高胰岛素血症性低血糖症研究进展

婴儿持续性高胰岛素血症性低血糖症(PHHI)是婴儿持续性低血糖最常见原因,其发病机制涉及影响胰岛β细胞胰岛素分泌的多个基因突变,表现为2种组织学类型(弥漫型和局灶型病变),是一大类病因各异的遗传性疾病.临床表现为婴儿期低血糖伴胰岛素不适当地过度分泌及低酮体、低脂肪酸血症,可造成严重的低血糖脑损伤及继发糖尿病.二氮嗪作为一线治疗药物可以抑制胰岛素分泌,在部分患者中有效.药物治疗无效可行胰腺次全或局部切除术以减缓脑损伤,术前或术中确定病理类型对决定手术方式和判断预后十分重要.     

非胰岛β细胞瘤高胰岛素血症性低血糖的新观点

低血糖症十分常见。非胰岛β细胞瘤的高胰岛素血症性低血糖症的病因研究在近年来有了新的进展，各种不同的亚型在临床表现上各有不同的特征。了解这些临床特征对提高低血糖症的诊治水平有重要的意义。     

胰岛细胞结节样增生伴低血钾及低血糖一例

对一例反复发生低血糖、低钾血症、无腹泻症状的女性胰岛细胞结节样增生患者行胰体尾部切除术，切除增生的胰岛细胞后，该患者的血糖和血钾水平恢复正常。     

Hyperinsulinemic hypoglycemia due to adult nesidioblastosis in insulin-dependent diabetes

INTRODUCTION Persistent hyperinsulinemic hypoglycemia (PHH) caused by functionally defectice β-cells in the setting of anesidioblastosis is the most common pathological substrate in newborns, whereas in adults, PHH is usually caused by solitary insulinomas[1-3]. Several genetic abnormalities were identified as the causes of PHH in infancy. The most important mutations are in the β-cell sulfonylurea receptor (SUR1) gene and encoding proteins composing the ATP- sensitive potassium ch…     

Evidence of unrestrained beta-cell proliferation and neogenesis in a patient with hyperinsulinemic hypoglycemia after gastric bypass surgery

ABSTRACT

Hyperinsulinemic hypoglycemia syndrome (HIHG) is a rare complication of roux-en-Y gastric bypass surgery. The pathology is associated with an excessive function of pancreatic beta-cells, and requires pancreas resection in patients that are recalcitrant to nutritional and pharmacological interventions. The exact prevalence is not clearly understood and the underlying mechanisms not yet fully characterized. We herein sought to perform histological and molecular examination of pancreatic sections obtained from a patient who developed HIHG as a complication of gastric bypass compared to 3 weight-matched controls. We studied markers of cellular replication and beta-cell differentiation by immunohistochemistry and immunofluorescence. HIHG after gastric bypass was characterized by a profound increase in beta-cell mass. Cellular proliferation was increased in islets and ducts compared to controls, suggesting unrestrained proliferation in HIHG. We also detected beta-cell differentiation markers in duct cells and occasional duct cells displaying both insulin and glucagon immunoreactivity. These histological observations suggest that beta-cell differentiation from ductal progenitor cells could also underly beta-cell mass expansion in HIHG. Altogether, our results can be construed to demonstrate that HIHG after gastric bypass is characterized by abnormal beta-cell mass expansion, resulting from both unrestrained beta-cell replication and neogenesis.     

Islet cell hyperplasia: an unusual cause of hypoglycemia in an adult

This is a case presentation of a 32-year-old man with a one year history of symptomatic hypoglycemia and documented elevations of his fasting plasma insulin to glucose ratio, caused by islet cell hyperplasia. Islet cell hyperplasia is a common cause of hypoglycemia in the pediatric population, but is very rare in adults. As in the pediatric group, adults should be treated with subtotal (75-85%) resection of the pancreas and with diazoxide for symptomatic recurrence of hypoglycemia. We suggest that the term islet cell hyperplasia is preferred to designate a diffuse proliferation of endocrine cells that may express itself with different morphologic patterns, varying from case to case. Islet cell hyperplasia, therefore, comprises nesidioblastosis, endocrine cell budding from ductal structures, as well as islet and islet cell hypertrophy, septal islets, islet dysplasia, and adenomatosis. Immunohistochemistry is a valuable method for the demonstration of the polymorphic hormonal content of the proliferated islet cells. We propose that the term nesidioblastosis, previously used to describe some similar cases, should be avoided because of confusion about its definition.     

Diagnosis of pancreatic islet hyperplasia causing hypoglycemia in a patient with portacaval anastomosis

A patient with biopsy-proved biliary cirrhosis and previous gastrojejunostomy and portacaval anastomosis experienced episodes of severe hypoglycemia. She was found to have hyperinsulinemia and hyperglucagonemia. An oral glucose tolerance test showed postga?trectomy hypoglycemia. Results of the intravenous tolbutamide test were diagnostic for insulinoma, but results of the intravenous glucagon test and prolonged fast (96 hours) were not. Failure, on two occasions, to suppress C-peptide normally during insulin-induced hypoglycemia led to a diagnosis of pancreatogenous hyperinsulinemia. The pancreas showed a 10-fold increase in islet volume, with intensely positive staining with anti-insulin and anti-glucagon antiserums in addition to anti-somatostatin and anti-pancreatic polypeptide antiserums. Incidental findings at pancreatic exploration were a mesothelioma, which did not stain with anti-insulin antiserum, and, at autopsy one year later, a hepatoma.     

The relation between HbA1c and hypoglycemia revisited; a secondary analysis from an intervention trial in patients with type 1 diabetes and impaired awareness of hypoglycemia

Aims

We aimed to re-assess the previously shown but recently disputed association between HbA1c and severe hypoglycemia.

Acinar cell carcinoma of the pancreas associated with hypoglycemia: Involvement of "big" insulin-like growth factor-II

Apart from insulinomas, pancreatic tumors are rarely complicated by hypoglycemia and some may produce insulin-like growth factor II (IGF-II). To our knowledge, IGF-II-producing pancreatic tumors associated with hypoglycemia have not been reported previously. We describe what we believe to be the first case of "big" IGF-II-producing pancreatic acinar cell carcinoma. A 68-year-old man presented with a history of recurrent hypoglycemia. Abdominal computed tomography scan and magnetic resonance imaging showed a mass, approximately 5 cm in diameter, in the tail of the pancreas and two low-density areas in the liver. Low serum glucose was associated with low insulin levels and high levels of hormones (i.e., glucagon and IGF-II) that are functionally opposite to insulin. Although serum IGF-II level was within the normal range, most IGF-II was of the high molecular weight form, as determined by Western immunoblot analysis. Based on these findings, a diagnosis of hypoglycemia induced by IGF-II-producing pancreatic tumor was made. Surgery was not possible because of the patient's poor general condition. The patient ultimately died as a result of malignant cachexia. At autopsy, a yellowish-white tumor was found in the tail of the pancreas, and a histopathologic diagnosis of acinar cell carcinoma was made. Immunohistologically, the tumor cells contained IGF-II in an irregular staining pattern, suggesting that the hypoglycemia was caused by a pancreatic tumor producing "big" IGF-II. Received Dec. 17, 1997; accepted Mar. 17, 1998     

Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine(more often), stomach, large intestine, or rectum. The patho-genesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immu-nodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infec-tion, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointes-tinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germi-nal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submu-cosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodu-lar lymphoid hyperplasia is a risk factor for both intes-tinal and, very rarely, extraintestinal lymphoma. Someauthors recommend surveillance, however, the duration and intervals are undefined.     

Malrotation causing duodenal chronic obstruction in an adult

Congenital duodenal obstruction is rare in adulthood. An unusual presentation of this condition has led to difficult preoperative diagnosis. We present a case of proximal jejunal obstruction by a congenital band in an adult and review the literature.     

Islet amyloid polypeptide promotes beta-cell proliferation in neonatal rat pancreatic islets

Aims/hypothesis: We aimed to clarify the role of islet amyloid polypeptide, which is expressed at early embryonic onset, in the proliferation and cell death of neonatal islet cells. Methods: Fetal islets were prepared from pregnant rats on gestational day 21. Islets were cultured in RPMI 1640 (11.1 mmol/l glucose) + 10 % fetal calf serum (FCS) for 48 h, followed by a 24-h culture period in RPMI 1640 (5.6 mmol/l glucose) + 1 % FCS. The islets were then exposed to rat islet amyloid polypeptide (1–10 nmol/l) for 24 h. Results: Iselt amyloid polypeptide increased islet DNA synthesis (dpm/μg of DNA · 6 h) (control 1 % FCS: 3634 ± 662; 1 nmol/l 6347 ± 1535; 10 nmol/l 5157 ± 769; p < 0.05 islet amyloid polypeptide vs control). In accordance with this, a doubling of the autoradiographic labelling index was seen in immunocytochemically stained islet beta cells after exposure to 1 and 10 nmol/l islet amyloid polypeptide. Islet amyloid polypeptide at 1 nmol/l increased the islet insulin content (202 ± 25 % of control; p < 0.01) and the 24-h medium insulin concentration (1 nmol/l islet amyloid polypeptide: 143 ± 19 % of control; p < 0.05) but at 10 nmol/l islet amyloid polypeptide these changes did not attain statistical difference. Islet amyloid polypeptide did not have any marked effect on the islet cell death frequency, suggesting that islet amyloid polypeptide is a more potent promoter of proliferation than of programmed cell death. Conclusion/interpretation: Our data indicate islet amyloid polypeptide is a potential regulator of proliferation in neonatal pancreatic islet cells, an effect which can partly be attributed to the proliferation of beta cells. [Diabetologia (2001) 44: 1015–1018] Received: 14 March 2001 and in revised form: 7 May 2001     

Biologically active circulating proinsulin-like materials from an islet cell carcinoma patient

Summary Circulating immunoreactive insulin (IRI) material was obtained from a hypoglycemic patient with a pancreatic islet cell carcinoma. On gel filtration, 85% of this material eluted as a homogeneous proinsulin peak (PLM) and 15% as insulin. On polyacrylamide gel electrophoresis, in addition to a small amount of insulin, two peaks were obtained. One had the migration of intact human proinsulin. The second electrophoresed as an intermediate species compatible with desdipeptide proinsulin. Trypsin treatment of PLM resulted in IRI material eluting as insulin on gel filtration. When comparable amounts of IRI material were tested, PLM showed about one half of the biological activity of porcine insulin in the rat hemidiaphragm system. No evidence of conversion to insulin was found after PLM had exerted its biological activity. In addition to large amounts of proinsulin, islet cell tumors may secrete significant amounts of intermediate species into the circulation.Supported by VA Research Funds and NIH Grant AM 11578     

Interrupted aortic arch in an adult female

Interrupted aortic arch is a rare and usually lethal malformation, representing approximately 1% of congenital heart disease. This presents as a missing segment of the aortic arch and is divided into three types: A-called extreme form of coarctation, and is characterized by disruption of aorta's continuity distal to the left subclavian artery (30-40%), B-disruption between the left subclavian and the left carotid arteries (55-60%), and C-the most uncommon type, interruption proximal to the left common carotid artery. The suspicion of coarctation of the aorta can be made from a combination of physical findings including systolic ejection murmur, the murmurs of collateral blood vessels, diminished or absent femoral pulse, and difference in blood pressure between arms and legs. Interrupted aortic arch is an extremely rare anomaly in adult patients. To our knowledge, the world medical literature contains only about 13 reports of interrupted aortic arch diagnosed in adults.     

Giant mesenchymal hamartoma of the liver in an adult

We report a case of hepatic mesenchymal hamartoma in an adult; this condition is extremely rare, with only 15 cases having been reported in the English-language literature worldwide. The patient was a 36-year-old woman who was seen at her local hospital for upper abdominal distension. A giant multilocular cystic tumor, which had almost entirely replaced the normal parenchyma of the right lobe of the liver, was diagnosed. She was referred to our hospital, where, with a diagnosis of biliary cystadenoma, the tumor was successfully removed by right hemihepatectomy. After an uneventful postoperative course, the patient was discharged from our hospital. On histological examination, the tumor consisted of numerous cystic lesions without epithelial lining cells; hepatocytes, bile duct, and vascular components, without either lobular structure or atypia, were observed in the pseudocyst wall, leading to a diagnosis of hepatic mesenchymal hamartoma. There have been a few previously reported cases of multifocal hepatic mesenchymal hamartoma reappearing in the remaining liver after hepatectomy, although these cases are considered to be extremely rare. Therefore, periodic follow-up will be necessary for the patient.     

Mucosal hyperplasia in an uncovered portion of partially covered metal stent

Covered self-expandable metal stents were developed to overcome tumor in-growth through the metal mesh.Stent migration is one of their malfunctions.Recently,the partially covered wallflex stent(PCWS) was developed with flared ends to prevent migration However,difficulty has been reported in its removal.We describe the removal of a PCWS embedded in mucosal hyperplasia at the uncovered proximal flared end,visualized by using SpyGlass cholangioscopy.