Congenital hyperinsulinism: diagnostic and management challenges in a developing country - case report (original) (raw)
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Clinical Features of 52 Neonates with Hyperinsulinism
New England Journal of Medicine, 1999
Background Neonatal hyperinsulinemic hypoglycemia is often resistant to medical therapy and is often treated with near-total pancreatectomy. However, the pancreatic lesions may be focal and treatable by partial pancreatic resection. Methods We studied 52 neonates with hyperinsulinism who were treated surgically. The type and location of the pancreatic lesions were determined by preoperative pancreatic catheterization and intraoperative histologic studies. Partial pancreatectomy was performed in infants with focal lesions, and near-total pancreatectomy was performed in those with diffuse lesions. The postoperative outcome was determined by measurements of plasma glucose and glycosylated hemoglobin and by oral glucosetolerance tests. Conclusions Among neonates with hyperinsulinism, about half may have focal islet-cell hyperplasia that can be treated with partial pancreatectomy. These neonates can be identified through pancreatic catheterization and intraoperative histologic studies.
Journal of pediatric surgery, 2018
Congenital Hyperinsulinism (HI) causes severe hypoglycemia in neonates and children. We reviewed our experience with pancreatectomy for the various types of HI. From 1998 to 2018, 500 patients with HI underwent pancreatectomy: 246 for focal HI, 202 for diffuse HI, 37 for atypical HI (16 for Localized Islet Nuclear Enlargement [LINE], 21 for Beckwith-Wiedemann Syndrome), and 15 for insulinoma. Focal HI neonates were treated with partial pancreatectomy. Patients with diffuse HI who failed medical management underwent near-total (98%) pancreatectomy. Atypical HI patients had pancreatectomies tailored to the PET scan and biopsy findings. The vast majority of pancreatectomies for focal HI were < 50%, and many were 2%-10%. 97% of focal HI patients are cured. For diffuse disease patients, 31% were euglycemic, 20% were hyperglycemic, and 49% required treatment for hypoglycemia; the incidence of diabetes increased with long-term follow-up. All 15 insulinoma patients were cured. Our approa...
Neonatal hyperinsulinism—Surgical and pathologic considerations
Journal of Pediatric Surgery, 1980
9 Hyperinsulinism in infancy is most often associated with a diffuse pancreatic lesion designated islet-cell dysmaturation syndrome. This disease is commonly associated with persistent hypoglycemia which usually results from inappropriate secretion of insulin. Urgent medical therapy consisting of hypertonic glucose infusion, frequent feeding, and diazoxide is mandatory in order to prevent central nervous system damage. Where medical means of therapy are not effective, an early 85% subtotal pancreatectomy with preservation of the spleen, is indicated. Nine infants who suffered from hyperinsulinism are reported. In two, medical measures were sufficient to control the disease. One of these patients in whom treatment was started late, remained slightly mentally retarded. Seven patients underwent 85% panereatectomy. In one of these, an additional 7.5% of the pancreas had to be removed and in a second patient total pancreatectomy was performed in order to control the disease. One patient died on the eighth postoperative day after acute gastric perforation. There was no evidence of residual brain damage in the patients who underwent subtotal pancreatectomy.
Congenital hyperinsulinism: current trends in diagnosis and therapy
Orphanet Journal of Rare Diseases, 2011
Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18 F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable.
American Journal of Clinical Pathology, 2016
Objectives: To quantify islet cell nucleomegaly in controls and tissues obtained from patients with congenital hyperinsulinism in infancy (CHI) and to examine the association of nucleomegaly with proliferation. Methods: High-content analysis of histologic sections and serial block-face scanning electron microscopy were used to quantify nucleomegaly. Results: Enlarged islet cell nuclear areas were 4.3-fold larger than unaffected nuclei, and the mean nuclear volume increased to approximately threefold. Nucleomegaly was a normal feature of pediatric islets and detected in the normal regions of the pancreas from patients with focal CHI. The incidence of nucleomegaly was highest in diffuse CHI (CHI-D), with more than 45% of islets containing two or more affected cells. While in CHI-D nucleomegaly was negatively correlated with cell proliferation, in all other cases, there was a positive correlation. Conclusions: Increased incidence of nucleomegaly is pathognomonic for CHI-D, but these cells are nonproliferative, suggesting a novel role in the pathobiology of this condition. Congenital hyperinsulinism in infancy (CHI) is the most common cause of persistent or recurrent hypoglycemia in early childhood and infancy. CHI is broadly characterized by the inappropriate release of insulin from pancreatic b cells for the level of glycemia and is associated with hypoglycemia-induced brain injury and adverse long-term neurologic outcomes in more than one-third of cases. 1-3 The hypoglycemia can be unresponsive to diazoxide, somatostatin analogues, and other medications, necessitating partial or near-total pancreatectomy. 1-3 Defects in several genes are identifiable causes of CHI, 4-6 but for many cohorts of patients with persistent disease, the genetic basis of disease is unknown, 7-11 ranging from 18% in Saudi Arabia 12 to greater than 60% in Australia 13 and China. 14 The most common origins of drug-unresponsive disease are due to inactivating mutations in either the ABCC8 or KCNJ11 genes. These encode subunits of adenosine triphosphate (ATP)-sensitive K þ channels in b cells and result in loss of channel function, leading to inappropriate changes in the b-cell membrane potential, calcium influx, and insulin release. 15 In addition to a spectrum of severities and genetic causes, CHI also has anatomopathologic diversity, 16 which means that surgical management can be selectively deployed if affected parts of the pancreas can be identified. In patients with diffuse CHI (CHI-D), all islets throughout the pancreas are affected, 16 whereas in patients with focal CHI (CHI-F), b-cell defects are localized to a topographical region caused by hyperplasia due to the loss of maternally imprinted genes. 17 Recently, a third form of the condition has been described, accounting for approximately 10% to
CONGENITAL HYPERINSULINISM–SURGICAL TREATMENT AND COMPLICATIONS
Acta Chirurg, 2011
Congenital hyperinsulinism is a common cause of persistent hypoglycaemia in neonates. Cases resistant to medicamentous therapy require surgical treatment, where the greatest challenge is to differentiate focal from diffuse forms of the disease and to localize the focal lesion. PET-scan, selective arterial stimulation and venous sampling (ASVS) and intraoperative frozen sections examination are used to determine the type. Partial pancreatectomy for focal forms has lower complication rate and diabetes mellitus development than radical near-total pancreatectomy for diffuse forms. We report a case of a 6-month-old boy with focal form of CHI with special emphasis on surgical complications of pancreas resection together with their management.
Congenital hyperinsulinism: management and outcome, a single tertiary centre experience
European Journal of Pediatrics, 2020
Hyperinsulinemic hypoglycaemia (HH) is the most frequent cause of persistent hypoglycaemia in neonates and infants. The most severe forms of HH are inherited and referred to as congenital hyperinsulinism (CHI). Diazoxide is the mainstay of treatment, with surgery being an option in appropriate cases. To describe the management and outcome of patients with CHI within our service. Children referred to or attending HH clinic between 2009 and 2017 were identified. Clinical course, genetics and interventions were documented. A total of 39 children were identified, and seven patients with secondary and syndromic HH were excluded. Most were born with an appropriate weight for gestational age (62.5%). Diazoxide was started in all patients; however, 7 did not respond and required octreotide/continuous feeding, with 6/7 requiring surgery. Genetic mutations were detected in 12/32 (37.5%). Hyperinsulinism resolved in conservatively treated patients within 12 months in 11/32 (34.3%) compared to 14/32 (43.7%) requiring more than 12 months of medication. A total of 7 patients underwent pancreatectomy. Conclusion: Although LGA and SGA are risk factors, most babies in our cohort are born AGA. A genetic mutation does not exclude medical remission; long-term conservative treatment of CHI is feasible as surgery does not guarantee complete remission. What is Known: •Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder that is the most common cause of permanent hypoglycaemia in infants and children. •Identification of genetic mutations and the use of 18F-DOPA PET scan when feasible lead to better outcomes. What is New: •The study describes clinical criteria, management and outcome of large number of patients with CHI in single tertiary centre. •Conservative treatment is feasible without the need for surgery, with HH resolving in over 30% within 12 months, irrespective of genetic mutation.
Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism—The UK Perspective
Journal of the Endocrine Society, 2022
Context In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic β-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery. Objective We describe surgical and nonsurgical outcomes of focal CHI in a national cohort. Methods Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018. Results Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (...
The Heterogeneity of Focal Forms of Congenital Hyperinsulinism
The Journal of Clinical Endocrinology & Metabolism, 2012
Background: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia due to unregulated insulin secretion from pancreatic -cells. Histologically, there are two major subgroups, focal and diffuse. Focal CHI is typically unresponsive to diazoxide and can be cured with surgical removal of the focal lesion.
Frontiers in Endocrinology
Background: Congenital Hyperinsulinism (CHI) is an important cause of severe and persistent hypoglycaemia in infancy and childhood. The focal form (CHI-F) of CHI can be potentially cured by pancreatic lesionectomy. While diagnostic characteristics of CHI-F pancreatic histopathology are well-recognized, correlation with clinical phenotype has not been established. Aims: We aimed to correlate the diversity in clinical profiles of patients with islet cell organization in CHI-F pancreatic tissue. Methods: Clinical datasets were obtained from 25 patients with CHI-F due to ABCC8/KCNJ11 mutations. 18 F-DOPA PET-CT was used to localize focal lesions prior to surgery. Immunohistochemistry was used to support protein expression studies. Results: In 28% (n = 7) of patient tissues focal lesions were amorphous and projected into adjoining normal pancreatic tissue without clear delineation from normal tissue. In these cases, severe hypoglycaemia was detected within, on average, 2.8 ± 0.8 (range 1-7) days following birth. By contrast, in 72% (n = 18) of tissues focal lesions were encapsulated within a defined matrix capsule. In this group, the onset of severe hypoglycaemia was generally delayed; on average 46.6 ± 14.3 (range 1-180) days following birth. For patients with encapsulated lesions and later-onset hypoglycaemia, we found that surgical procedures were curative and less complex. Conclusion: CHI-F is associated with heterogeneity in the organization of focal lesions, which correlates well with clinical presentation and surgical outcomes.