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Mutations in the insulin receptor (INSR) gene are associated with insulin resistance and hyperglycaemia. Various autosomal dominant heterozygous INSR mutations leading to hyperinsulinemic hypoglycaemia (HH) have been described in adults and children (more than 3 years of age) but not in the neonatal period. Family 1: A small for gestational age (SGA) child born to a mother with gestational diabetes presented with persistent hypoglycaemia, was diagnosed with HH and responded well to diazoxide treatment. Diazoxide was gradually weaned and discontinued by 8 months of age. Later, the younger sibling had a similar course of illness. On genetic analysis a heterozygous INSR missense variant p.(Met1180Lys) was found in the siblings, mother and grandfather but not in the father. Family 2: A twin preterm and SGA baby presented with persistent hypoglycaemia, which was confirmed as HH. He responded to diazoxide, which was subsequently discontinued by 10 weeks of life. Genetic analysis revealed a novel heterozygous INSR missense variant p.(Arg1119Gln) in the affected twin and the mother. Family 3: An SGA child presented with diazoxide responsive HH. Diazoxide was gradually weaned and discontinued by 9 weeks of age. Genetic analysis revealed a novel heterozygous INSR p.(Arg1191Gln) variant in the proband and her father. We report, for the first time, an association of INSR mutation with neonatal HH responsive to diazoxide therapy that resolved subsequently. Our case series emphasizes the need for genetic analysis and long-term follow up of these patients.

Development of pulmonary hypertension after initiation of diazoxide for the treatment of neonatal hyperinsulinemic hypoglycemia is a rare, but previously described association. Risk factors for development of diazoxide-associated pulmonary hypertension include lower gestational age and congenital heart disease. This novel case report describes an infant with noncompaction cardiomyopathy who developed pulmonary hypertension shortly after initiation of diazoxide for hyperinsulinemic hypoglycemia which resolved upon cessation of the drug. This case highlights the benefit of having pre-treatment knowledge of underlying cardiac anatomy and makes a case for routine echocardiographic screening for neonates initiating diazoxide treatment.

We report the clinical and neuroradiological findings in a young boy harboring the 9p deletion syndrome including the novel findings of thalamic infarction and germinal matrix haemorrhage and neonatal hyperinsulinemic hypoglycemia. Both the hypoglycemic events and the ventriculomegaly found in this patient have previously only been reported in two patients, while the thalamic infarction and germinal matrix haemorrhage are novel features.

On page 3335 of the article cited above, funding information was added for author Frances M. Ashcroft. …

Neste artigo será relatado um caso de Hipoglicemia Hiperinsulinêmica Persistente Infantil (HHPI) e após seguirá uma revisão de literatura sobre tal assunto. Trata-se de uma recém-nascida que iniciou episódios de hipoglicemia nas primeiras 24 horas de vida e foi medicada com octreotide com boa resposta a esta terapêutica até o momento. A HHPI é a principal causa de hiperinsulinismo persistente na infância e pode ser extremamente deletéria ao desenvolvimento do sistema nervoso central. Há atualmente poucas opções de tratamento clínico, com eficácia muito variada, e o octreotide parece ser a melhor delas antes que tenha que ser realizada a terapêutica cirúrgica. Hoje em dia já é possível uma adequada diferenciação pré-operatória entre hiperinsulinemia de origem focal e difusa e isso permite a indicação precisa de pancreatectomia parcial nos casos focais, garantindo um maior sucesso do tratamento e reduzindo a ocorrência de efeitos adversos pós-operatórios. This paper presents a clinical case of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and a literature review on this subject. We report on a newborn who presented with hypoglycemic episodes in her first 24hs of life and was treated successfully with octreotide until the moment. PHHI is the most common cause of persistent hyperinsulinism in infancy and can be hazardous for the development of the central nervous system. There are few current options for clinical treatment, with variable efficacy, and octreotide seems to be the best option before surgical treatment, the only way to control the disease. Preoperative evaluation allows one to adequately distinguish between focal or diffuse processes and suggests the extension of pancreatic resection, improving surgical results and reducing the incidence of postoperative sequelae. Partial pancreatectomy is the procedure of choice in focal disease.

Background and Aims Sulfonylureas inhibit the ATP-sensitive potassium (K ATP ) channel, are insulinogenic, and close the fetal ductus arteriosus. Diazoxide, a K ATP channel opener, is used for neonatal hyperinsulinemic hypoglycemia, and has been associated with the reopening of the ductus arteriosus. The aim of this study is to clarify ductus-opening effect of diazoxide. Methods Neonatal rats were delivered by caesarian section near-term and incubated at 34°C. Diazoxide and pinacidil, another K ATP channel opener, were injected intraperitoneally immediately, or at one hour, or at four hours postnatally, and the ductus was studied 0.5, and 1 hour later, with a rapid whole-body freezing method. Results Diazoxide and pinacidil both induced hyperglycemia. Diazoxide and pinacidil delayed neonatal ductus closure following injection immediately after birth. At 2 hours, the control ductus was closed, whereas the ductus treated with 100 mg/kg of diazoxide at birth was widely patent with a diameter 40% of the fetal ductus. Ductus diameter at 60 minutes postnatally dilated from 10% to 40% with diazoxide. Diazoxide given to the closed ductus at 4 hours after birth did not open reopen it. The ductus was more sensitive to pinacidil than to diazoxide. Conclusions Diazoxide and pinacidil open the closing ductus arteriosus of the neonatal rat. This study demonstrates that opening of K ATP channels results in opening of the ductus arteriosus, indicating that the K ATP channel is physiologically and pharmacologically important in ductus opening. The ductus should be checked in the neonate before and after treatment with diazoxide.

In contrast to glucagon, cortisol is a secondary contra-insulin hormone in the adult. In continuing studies of neonatal hyperinsulinemic hypoglycemia, we hypothesized comparable relative ineffectiveness. Twenty five spontaneously delivered neonatal lambs weighing 4.9±1.0 kgs (M±SD) were infused at 5.0±0.9 days with 100 μCi D-[6-3H2] glucose in 0.9% NaCl by prime constant infusion to measure glucose production (GP). After a preperturbation period, infusion of 2.0 mU·kg-1min-1 insulin (I) produced hyperinsulinemic hypoglycemia and was combined with 1.0 μg·kg-1min-1 somatostatin (SRIF) to block insulin, glucagon and growth hormone release. Infusion of 2.0 ng·kg-1 min-1 glucagon (G) with I and SRIF isolated the glucagon effect. The addition of metyrapone (M) blocked cortisol release to evaluate the absence of cortisol. Controls (C) received only the isotope. Representative data are from the end of the perturbation.Table

INFLUENCE OF GLUCAGON AS A CONTRA INSULIN HORMONE IN NEONATAL HYPERINSULINEMIC HYPOGLYCEMIA. † 506