11/24. Congenital disorder of glycosylation id presenting with hyperinsulinemic hypoglycemia and islet cell hyperplasia.CONTEXT: Inborn errors in protein glycosylation, such as the congenital disorders of glycosylation (CDGs), generate multifaceted syndromes that impair many organ systems. We here report the diagnosis of the third known patient with CDG-Id. RESULTS: The patient's phenotype was extremely severe, and she succumbed at 19 d of age. Leading features included hyperinsulinemic hypoglycemia, and autopsy revealed islet cell hyperplasia with increased beta-cell mass. Other features were a Dandy-Walker malformation, facial dysmorphisms, and profound hypotonia. The patient carried a novel homozygous point mutation (512G>A) in the hALG3 gene, which encodes a mannosyltransferase. Lentiviral complementation with wild-type hALG3 corrects the biochemical defect in the patient's fibroblasts. CONCLUSIONS: Our findings underscore the importance of proper glycosylation in several major organ systems and emphasize that CDG should be ruled out in patients with persistent hyperinsulinemic hypoglycemia of unknown etiology.- - - - - - - - - - ranking = 1keywords = hyperplasia (Clic here for more details about this article) |
12/24. congenital hyperinsulinism and mosaic abnormalities of the ploidy.BACKGROUND: congenital hyperinsulinism and beckwith-wiedemann syndrome both lead to beta islet hyperplasia and neonatal hypoglycaemia. They may be related to complex genetic/epigenetic abnormalities of the imprinted 11p15 region. The possibility of common pathophysiological determinants has not been thoroughly investigated. OBJECTIVE: To report abnormalities of the ploidy in two unrelated patients with congenital hyperinsulinism. methods: Two patients with severe congenital hyperinsulinism, one overlapping with beckwith-wiedemann syndrome, had pancreatic histology, ex vivo potassium channel electrophysiological studies, and mutation detection of the encoding genes. The parental genetic contribution was explored using genome-wide polymorphism, fluorescent in situ hybridisation (FISH), and blood group typing studies. RESULTS: Histological findings diverged from those described in focal congenital hyperinsulinism or beckwith-wiedemann syndrome. No potassium channel dysfunction and no mutation of its encoding genes (SUR1, KIR6.2) were detected. In patient 1 with congenital hyperinsulinism and beckwith-wiedemann syndrome, paternal isodisomy for the whole haploid set was homogeneous in the pancreatic lesion, and mosaic in the leucocytes and skin fibroblasts (hemihypertrophic segment). Blood group typing confirmed the presence of two erythroid populations (bi-parental v paternal only contribution). Patient 2 had two pancreatic lesions, both revealing triploidy with paternal heterodisomy. karyotype and FISH analyses done on the fibroblasts and leucocytes of both patients were unremarkable (diploidy). CONCLUSIONS: Diploid (biparental/paternal-only) mosaicism and diploid/triploid mosaicism were present in two distinct patients with congenital hyperinsulinism. These chromosomal abnormalities led to paternal disomy for the whole haploid set in pancreatic lesions (with isodisomy or heterodisomy), thereby extending the range and complexity of the mechanisms underlying congenital hyperinsulinism, associated or not with beckwith-wiedemann syndrome.- - - - - - - - - - ranking = 0.2keywords = hyperplasia (Clic here for more details about this article) |
13/24. serum and pancreatic immunoreactive insulin (IRI) and proinsulin-like component (PLC), serum IRI and PLC response to different stimuli in normal subjects and organic hyperinsulinism.The serum levels of total immunoreactive insulin (IRI) and proinsulin-like component (PLC) in the fasting state and following the administration of insulin secretagogues in 5 patients with organic hyperinsulinism and age and sex matched normal subjects are reported. diagnosis of organic hyperinsulinism could be established in all instances on the basis of the inappropriately high total serum IRI levels for the corresponding blood glucose values; such an abnormal relationship was not seen in normal subjects, and was further enhanced by insulin secretagogues. Unrestrained insulin secretion in organic hyperinsulinism was enhanced following the administration of glucose, tolbutamide, glucagon or amino acids; the last 2 stimuli are known to be ineffective in causing insulin secretion in the presence of hypoglycemia in normal subjects. Four patints had insulinomas and one probably had islet cell hyperplasia or abnormal function of islet cells. chromatography of serum IRI to quantitate PLC is a useful adjunct to the diagnosis of organic hyperinsulinism as in the fasting state the proportion of PLC is always elevated, above the normal range of 5-22%. Following the administration of insulin secretagogues there was pronounced increase in total serum IRI in organic hyperinsulinism but the proportion of PLC generally decreased, suggesting thereby that mojor increase in IRI was due to release of stored granular IRI which is known to have a low proportion of PLC.- - - - - - - - - - ranking = 0.2keywords = hyperplasia (Clic here for more details about this article) |
14/24. Neonatal and infantile hypoglycemia due to insulin excess: new aspects of diagnosis and surgical management.Persistent hypoglycemia in the neonate and young infant usually results from inappropriate, excessive secretion of insulin, or a deficiency of one of the hepatic gluco-regulatory enzymes. hypoglycemia due to hyperinsulinism, whether associated with nesidioblastosis, islet cell hyperplasia, adenoma or normal islets, may have devastating consequences in this age group and demands recognition and effective treatment. Medical management consisting primarily of frequent feeding, the intravenous infusion of glucose and the administration of glucagon, glucocorticoids, epinephrine, and diazoxide is often ineffective and may be punctuated by repeated episodes of hypoglycemia, convulsions, and central nervous system damage. Although subtotal-total pancreatectomy is effective in restoring blood sugar to normal, almost half of the reported patients are mentally retarded. This may be due in part to unwarranted delays in performing pancreatectomy. Experience with 6 patients undergoing subtotal--total pancreatectomy for intractable hypoglycemia supports the contention that this procedure is effective. A euglycemic state was restored in all 6 patients and there was no evidence of residual central nervous system damage. The spleen should be preserved in view of its importance in maintaining normal immunodefense mechanisms.- - - - - - - - - - ranking = 0.2keywords = hyperplasia (Clic here for more details about this article) |
15/24. Hyperinsulinemic hypoglycemia of the neonate associated with persistent fetal histology and function of the pancreas.Early in development, the fetal pancreas is characterized by the presence of two distinct generations of endocrine cells and a B-Cell mass that is unresponsive to acute changes in circulating glucose levels. Near the end of intrauterine development, the normal pancreas has "matured" and contains a single generation of endocrine cells and B-Cells that are responsive to changes in glucose concentrations. Recent microscopic examination of resected pancreatic tissue from an infant with hyperinsulinemic hypoglycermia revealed a combination of all three of the currently accepted findings in this neonatal condition: hyperplasia, adenomatosis, and nesidioblastosis. These observations prompted the following hypothesis: When compared to the usual histology of the developing pancreas, nesidioblastosis may be interpreted as an abnormal continuation of normal proliferation of endocrine cells; hyperplasia may be a specific overproduction of the Secondary islands of Langerhans; and adenomatosis may be an abnormal continuation or overgrowth of the Primary Island of Langerhans. Such extrapolation suggests that infants with hyperinsulinemic hypoglycemia may represent a failure in the normal histological and functional maturation of the endocrine portion of the fetal pancreas.- - - - - - - - - - ranking = 0.4keywords = hyperplasia (Clic here for more details about this article) |
16/24. Pancreatic nesidioblastosis in adults. Report of a patient with hyperinsulinemic hypoglycemia.Hyperinsulinemic hypoglycemia in neonates occurs most commonly secondary to nesidioblastosis, a persistence of fetal development of the endocrine cells of the pancreas. In adults, hyperinsulinemic hypoglycemia is usually due to insulinoma or beta-cell hyperplasia. nesidioblastosis arising in adults has only recently been reported. An adult patient with nesidioblastosis has been described. The light and electron microscopic films of this entity are shown in detail, and the embryology and treatment are discussed. Further understanding of this newly described disease entity will require research on factors that regulate the differentiation of beta cells of the pancreas.- - - - - - - - - - ranking = 0.2keywords = hyperplasia (Clic here for more details about this article) |
17/24. Hyperinsulinism after removal of a pheochromocytoma.The finding of hypoglycemia after the surgical removal of a pheochromocytoma in two patients in a previous study led to monitoring of the serum glucose and plasma c-peptide levels in two other patients with a pheochromocytoma and one with unilateral adrenocortical hyperplasia. In the two patients with a pheochromocytoma endogenous insulin secretion, as measured by a c-peptide assay, was suppressed before removal of the tumours and resumed immediately after removal. The serum glucose levels decreased in these patients, but sufficient intravenous administration of glucose prevented postoperative hypoglycemia. In the patient with adrenocortical hyperplasia the plasma c-peptide level was not decreased before tumour removal, nor did it increase abruptly following removal. It therefore seems likely that the rapid fall in the serum glucose level following removal of a pheochromocytoma is caused by prompt resumption of beta-cell activity, with rebound hyperinsulinism.- - - - - - - - - - ranking = 0.4keywords = hyperplasia (Clic here for more details about this article) |
18/24. Neonatal pancreatic beta-cell hyperplasia: report of a case with failure of diazoxide and benefit of early subtotal pancreatectomy.A newborn infant with pancreatic beta-cell hyperplasia had persistent hypoglycemia due to hyperinsulinism. After medical management, including the use of diazoxide and constant glucose infusions had proved ineffective, a subtotal pancreatectomy was curative. Cumulative experience seems to indicate that there should be little delay in performing a subtotal pancreatectomy when aggressive medical management cannot maintain normoglycemia in a neonate.- - - - - - - - - - ranking = 1keywords = hyperplasia (Clic here for more details about this article) |
19/24. Nesidiodysplasia: an unusual cause of hyperinsulinemic hypoglycemia in adults.Herein, we report two cases of pancreatic nesidiodysplasia, an extremely rare cause of hyperinsulinemic hypoglycemia in adults. The first case was a 43-year-old, nonobese female with recurrent hypoglycemia after 10% distal pancreatectomy with splenectomy performed 16 years previously for insulinoma. Three suspect tumors were found on the preoperative angiograms and second operation, but the pathologic finding revealed diffusely scattered microscopic nodules with a background of nesidiodysplasia. The second case was a 52-year-old female with a five-year history of hypoglycemia. Extensive diagnostic procedures revealed a suspect insulinoma over the pancreatic body. The histology confirmed diffuse nesidiodysplasia. Both cases were diagnosed as insulinoma before surgical intervention because of the hypoglycemic symptoms, high insulin/glucose ratio and the positive image studies. The pathologic findings were characterized by the budding of islet cells from the pancreatic duct epithelium with diffuse islet hyperplasia. Both patients remained well after 75% to 80% pancreatectomy with no recurrence of hypoglycemia. The etiology, pathology, preoperative work-up, and operative strategy of nesidiodysplasia are discussed.- - - - - - - - - - ranking = 0.2keywords = hyperplasia (Clic here for more details about this article) |
20/24. nesidioblastosis in an adult with hyperinsulinemic hypoglycemia.A 50-year-old Korean man with repeated episodes of temporary loss of consciousness was diagnosed as having hyperinsulinemic hypoglycemia. Under the tentative diagnosis of insulinoma, localization procedures were carried out but no tumor was found. By percutaneous transhepatic portal venous sampling, no definite gradient in insulin concentration was found. During exploratory laparotomy no tumor was palpable in the pancreas, and intraoperative ultrasonography showed low echogenicity in the pancreatic head. Whipple's operation was performed and 70% of the proximal pancreas was removed. Histomorphometric examination of the resected specimen revealed graded hyperplasia of the islet cells. The most profuse hyperplasia was noted in the head with progressive decrease in the degree of hyperplasia to the body and tail. The patient remains euglycemic and tolerates 24 h fasting without any medication until 15 months after operation.- - - - - - - - - - ranking = 0.6keywords = hyperplasia (Clic here for more details about this article) |
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