Congenital Hyperinsulinism - Notes for the General Pediatrician.

Congenital hyperinsulinism (CHI) is a rare condition but is a common cause of severe and persistent hypoglycemia in early life. Prompt recognition of CHI is critical to prevent the impact of neuroglycopenia and consequent lifelong neurodisability. It is important to be alert to the possibility of CHI in newborn babies with recurrent hypoglycemia associated with high glucose requirements. Pediatricians are advised to mitigate the risk of hypoglycemia by early treatment with high concentration dextrose and intravenous glucagon infusions. Specific medical therapies with diazoxide and/or somatostatin receptor analogues may be commenced after the finding of detectable insulin at hypoglycemia, a biochemical characteristic of CHI. Early exploration of genetic etiology is recommended, chiefly in the search for a focal form, amenable to limited pancreatic surgery. Genetic ascertainment is also useful to understand the basis of disease, variable responses to medical therapies and escalation of conservative treatment to subtotal pancreatectomy. CHI is a heterogeneous disorder with varying natural history. Many newborns and infants with CHI have severe and complex illness features; their long-term care is best achieved through review at specialist centers.

Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus.

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.

Bridging the gaps: recent advances in diagnosis, care, and outcomes in congenital hyperinsulinism.

PURPOSE OF REVIEW: To highlight advances in congenital hyperinsulinism (HI), including newly described molecular mechanisms of disease, novel therapeutic interventions, and improved understanding of long-term outcomes. RECENT FINDINGS: Important advances have been made elucidating the molecular mechanisms responsible for HI. Non-coding variants in HK1 have been found to cause aberrant hexokinase expression. Inactivating mutations in SLC25A36 have been identified in children with features of the hyperinsulinism hyperammonemia syndrome. Low-level mosaic mutations in known HI genes have been detected in cases of 'genetic testing negative' HI. Identification and localization of focal HI lesions remains a priority, since focal HI can be cured with surgery. Use of 68 Ga-NODAGA-exendin-4 PET has been proposed to localize focal lesions. Additional studies are needed before this technique replaces 18 F-DOPA PET as standard of care. Treatment options for children with diffuse HI remain limited. The long-acting somatostatin analog, lanreotide, was shown to significantly improve glycemic control in a large series of children with HI. New therapies are under development, with promising preliminary results. Long-term quality of life and neurodevelopmental outcomes remain suboptimal. SUMMARY: Advanced genetic and epigenomic analytic techniques have uncovered novel molecular mechanisms of HI. Development of new drugs holds promise to improve long-term outcomes for individuals with HI.

Clinical Course and Outcome in Children with Congenital Hyperinsulinism.

BACKGROUND: Hyperinsulinism is the most common cause of persistent or recurrent neonatal hypoglycemia that may result in neurological deficits. The treatment goal in these patients is prevention of hypoglycemia to decrease mortality and morbidity. This study was done to determine the clinical course and outcome in children with congenital hyperinsulinism (CHI) referring to Mofid Children's Hospital from 2011 to 2017. METHODS: This study was done on 22 children with CHI referring to Mofid Children's Hospital from 2011 to 2017. The demographic, perinatal, clinical, laboratory, imaging, pharmacological, treatment and follow up data of these children were collected and analyzed. RESULTS: Among 22 children with CHI, the mortality rate was higher among those who received hydrocortisone versus those who did not receive hydrocortisone (46% versus 40%). CONCLUSION: According to the results of this study, hydrocortisone had a negative impact on the outcomes of these children, which is important in the management of hypoglycemia. The clinical course and outcome of children with CHI was better with medical compared to surgical treatment.

Global Registries in Congenital Hyperinsulinism.

Congenital hyperinsulinism (HI) is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children. There are many areas of need for HI research. Some of the most critical needs include describing the natural history of the disease, research leading to new and better treatments, and identifying and managing hypoglycemia before it is prolonged and causes brain damage or death. Patient-reported data provides a basis for understanding the day-to-day experience of living with HI. Commonly identified goals of registries include performing natural history studies, establishing a network for future product and treatment studies, and supporting patients and families to offer more successful and coordinated care. Congenital Hyperinsulinism International (CHI) created the HI Global Registry (HIGR) in October 2018 as the first global patient-powered hyperinsulinism registry. The registry consists of thirteen surveys made up of questions about the patient's experience with HI over their lifetime. An international team of HI experts, including family members of children with HI, advocates, clinicians, and researchers, developed the survey questions. HIGR is managed by CHI and advised by internationally recognized HI patient advocates and experts. This paper aims to characterize HI through the experience of individuals who live with it. This paper includes descriptive statistics on the birthing experience, hospitalizations, medication management, feeding challenges, experiences with glucose monitoring devices, and the overall disease burden to provide insights into the current data in HIGR and demonstrate the potential areas of future research. As of January 2022, 344 respondents from 37 countries consented to participate in HIGR. Parents or guardians of individuals living with HI represented 83.9% of the respondents, 15.3% were individuals living with HI. Data from HIGR has already provided insight into access challenges, patients' and caregivers' quality of life, and to inform clinical trial research programs. Data is also available to researchers seeking to study the pathophysiology of HI retrospectively or to design prospective trials related to improving HI patient outcomes. Understanding the natural history of the disease can also guide standards of care. The data generated through HIGR provides an opportunity to improve the lives of all those affected by HI.

Congenital Hyperinsulinism International: A Community Focused on Improving the Lives of People Living With Congenital Hyperinsulinism.

Congenital hyperinsulinism (HI) is a rare disease affecting newborns. HI causes severe hypoglycemia due to the overproduction of insulin. The signs and symptoms of hypoglycemia in HI babies is often not discovered until brain damage has already occurred. Prolonged hypoglycemia from HI can even lead to death. Disease management is often complex with a high burden on caregivers. Treatment options are extremely limited and often require long hospital stays to devise. Cascading from suboptimal treatments and diagnostic practices are a host of other problems and challenges that many with HI and their families experience including continued fear of hypoglycemia and feeding problems. The aim of this paper is (1) to describe the current challenges of living with HI including diagnosis and disease management told from the perspective of people who live with the condition (2), to provide family stories of life with HI, and (3) to share how a rare disease patient organization, Congenital Hyperinsulinism International (CHI) is working to improve the lives of HI patients and their families. CHI is a United States based nonprofit organization with a global focus. The paper communicates the programs the patient advocacy organization has put into place to support HI families through its virtual and in-person gatherings. The organization also helps individuals access diagnostics, medical experts, and treatments. CHI also raises awareness of HI to improve patient outcomes with information about HI and prolonged hypoglycemia in twenty-three languages. CHI drives innovation for new and better treatments by funding research pilot grants, conducting research through the HI Global Registry, and providing patient experience expertise to researchers developing new treatments. The organization is also the sponsor of the CHI Collaborative Research Network which brings medical and scientific experts together for the development of a patient-focused prioritized research agenda.

Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families.

BACKGROUND: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children, and carries a considerable risk of neurological damage and developmental delays if diagnosis and treatment are delayed. Despite rapid advances in diagnosis and management, long-term developmental outcomes have not significantly improved in the past years. CHI remains a disease that is associated with significant morbidity, and psychosocial and financial burden for affected families, especially concerning the need for constant blood glucose monitoring throughout patients' lives. RESULTS: In this review, we discuss the key clinical challenges and unmet needs, and present insights on patients' and families' perspective on their daily life with CHI. Prevention of neurocognitive impairment and successful management of patients with CHI largely depend on early diagnosis and effective treatment by a multidisciplinary team of specialists with experience in the disease. CONCLUSIONS: To ensure the best outcomes for patients and their families, improvements in effective screening and treatment, and accelerated referral to specialized centers need to be implemented. There is a need to develop a wider range of centers of excellence and networks of specialized care to optimize the best outcomes both for patients and for clinicians. Awareness of the presentation and the risks of CHI has to be raised across all professions involved in the care of newborns and infants. For many patients, the limited treatment options currently available are insufficient to manage the disease effectively, and they are associated with a range of adverse events. New therapies would benefit all patients, even those that are relatively stable on current treatments, by reducing the need for constant blood glucose monitoring and facilitating a personalized approach to treatment.

Congenital hyperinsulinism (CHI) is a rare disease that causes newborn babies and children to have low blood sugar because of the abnormal release of insulin. Insulin is a hormone produced by the pancreas that promotes the transfer of sugar from the blood into the body's cells. In a healthy person, insulin is released only after a meal when the level of blood sugar is high, but infants and children with CHI make insulin even if the blood sugar is low. This can lead to dangerously low blood sugar levels, which can cause brain damage if left untreated. Unfortunately, diagnosis and treatment are often delayed, resulting in avoidable brain damage and developmental delays in these children. CHI is associated with substantial stress and anxiety for the families, especially due to the need for frequent feeding and the fear of low blood sugars added to the constant need to measure blood sugar levels. This article discusses the most important challenges and unmet needs in this rare disease, including the limited treatment options, the side effects of available treatment options and the heavy psychological, social and financial burden on affected families. Effective screening of newborns for CHI needs to be improved, and quick referral to specialized treatment centers is necessary to ensure the best outcomes for patients and families. In addition, awareness of CHI has to be raised in all medical professions caring for newborns and infants, and new medications are urgently needed to ensure the best possible treatment for all patients with CHI.

Molecular Characterization and Management of Congenital Hyperinsulinism: A Tertiary Centre Experience.

BACKGROUND: There is limited data from India regarding medical management of congenital hyperinsulinism (CHI). OBJECTIVE: To study the molecular diagnosis, medical management and outcomes of children with CHI. STUDY DESIGN: Ambispective. PARTICIPANTS: Children with CHI admitted in from December, 2011 till March, 2020 at a tertiary care referral hospital. OUTCOMES: Clinical and genetic profile, treatment, and response. RESULTS: 42 children with a median age of 3 days (range 1 day to 6 years) were enrolled, of which 23 (54.7%) were diazoxide-responsive. Mutations were identified in 28 out of 41 (68.2%) patients. The commonest gene affected was ABCC8 in 22 patients. The pathogenic variant c.331G>A in ABCC8 gene was identified in 6 unrelated cases from one community. Good response to daily octreotide was seen in 13 of the 19 (68.4%) diazoxide-unresponsive patients. Monthly long-acting octreotide was initiated and daily octreotide could be stopped or tapered in 9 patients. Sirolimus was tried with variable response in 6 patients but was discontinued in 5 due to adverse effects. Four patients had focal CHI, of which one underwent partial pancreatic resection. The disease severity reduced with age and neurodevelopment was good in the patients with identifiable genetic defects who were optimally managed. CONCLUSIONS: Medical management of CHI is effective, if compliance can be ensured, with good quality of life and neurological outcomes.

Continuous Glucose Monitoring in the Management of Neonates With Persistent Hypoglycemia and Congenital Hyperinsulinism.

BACKGROUND: Persistent hypoglycemia is common in the newborn and is associated with poor neurodevelopmental outcome. Adequate monitoring is critical in prevention, but is dependent on frequent, often hourly blood sampling. Continuous glucose monitoring (CGM) is increasingly being used in children with type 1 diabetes mellitus, but use in neonatology remains limited. We aimed to introduce real-time CGM to provide insights into patterns of dysglycemia and to support the management of persistent neonatal hypoglycemia. METHODS: This is a single-center retrospective study of real-time CGM use over a 4-year period in babies with persistent hypoglycemia. RESULTS: CGMs were inserted in 14 babies: 8 term and 6 preterm infants, 9 with evidence of congenital hyperinsulinism (CHI). A total of 224 days of data was collected demonstrating marked fluctuations in glucose levels in babies with CHI, with a higher sensor glucose SD (1.52 ±â€…0.79 mmol/L vs 0.77 ±â€…0.22 mmol/L) in infants with CHI compared with preterm infants. A total of 1254 paired glucose values (CGM and blood) were compared and gave a mean absolute relative difference of 11%. CONCLUSION: CGM highlighted the challenges of preventing hypoglycemia in these babies when using intermittent blood glucose levels alone, and the potential application of CGM as an adjunct to clinical care.

Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management.

Congenital hyperinsulinism (CHI) is a rare disease characterized by an unregulated insulin release, leading to hypoglycaemia. It is the most frequent cause of persistent and severe hypoglycaemia in the neonatal period and early childhood. Mutations in 16 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, KCNQ1, CACNA1D, FOXA2, EIF2S3, PGM1 and PMM2) that are involved in regulating the insulin secretion from pancreatic ß-cells have been described to be responsible for the underlying molecular mechanisms of CHI. CHI can also be associated with specific syndromes and can be secondary to intrauterine growth restriction (IUGR), maternal diabetes, birth asphyxia, etc. It is important to diagnose and promptly initiate appropriate management as untreated hypoglycaemia can be associated with significant neurodisability. CHI can be histopathologically classified into diffuse, focal and atypical forms. Advances in molecular genetics, imaging techniques (18F-fluoro-l-dihydroxyphenylalanine positron emission tomography/computed tomography scanning), novel medical therapies and surgical advances (laparoscopic pancreatectomy) have changed the management and improved the outcome of patients with CHI. This review article provides an overview of the background, clinical presentation, diagnosis, molecular genetics and therapy for children with different forms of CHI.

Recent updates in the management of infants and children with hyperinsulinism.

PURPOSE OF REVIEW: To highlight recent advances in early diagnosis and the changing treatment paradigm for hyperinsulinism (HI) which can result in shorter hospitalizations, higher rates of cure and improved neurological outcome. RECENT FINDINGS: Recent literature has shown that following publication of the pediatric endocrinology society guidelines for diagnosing hypoglycemia there have been higher rates of diagnosis of acquired and genetic HI. Studies of neurological outcome have found that poor outcomes are associated with delay between initial hypoglycemia and instigation of treatment for HI, hypoglycemic seizures and frequency of glucose <20 mg/dL. Rapid genetic testing can decrease the time from the discovery of diazoxide unresponsiveness to referral to multidisciplinary centers with the availability of 18-F-L 3,4-Dihydroxyphenylalanine positron emission tomography (18F-DOPA PET). Proper selection of patients for 18F-DOPA PET and careful interpretation of the images can result in greater than 90% cure for patients with focal HI. SUMMARY: Recent advances in the early diagnosis of HI and rapid turnaround genetic testing can lead to prompt transfer to centers with multidisciplinary care teams where proper selection of patients for 18F-DOPA PET scan gives the best opportunity for cure for patients with focal disease. Minimizing severe hypoglycemia maximizes the opportunity for improved neurological outcome.

Congenital Hyperinsulinism.

Hyperinsulinemic hypoglycemia (HH) is fairly common in neonates, particularly those born to diabetic mothers and those who are either large or small for gestational age. Immediate management of the disease focuses on achieving normoglycemia through frequent high-calorie feedings and/or intravenous glucose administration. Glucagon may be used for unstable infants in whom intravenous access cannot be obtained and enteral feedings cannot be administered. HH that persists despite these interventions should raise concern for congenital hyperinsulinism (CHI), prompting clinicians to perform a thorough evaluation. CHI consists of a group of genetic disorders in which inappropriate insulin secretion results in persistent hypoglycemia. Defects can occur in the various genes that regulate the pathway for insulin secretion in the pancreatic ß-cells. Pharmacologic therapies are used for long-term management of the disease coupled with either curative or therapeutic surgical intervention. Because of the developing brain's high demand for glucose, these infants are at increased risk for hypoglycemic brain injury. This review will describe the pathogenesis of CHI, outlining the more common genetic mutations and associated syndromes. We will also discuss the clinical presentation, diagnosis, and management of CHI while providing insight into the overall prognosis.

Clinical characteristics, outcome, and predictors of neurological sequelae of persistent congenital hyperinsulinism: A single tertiary center experience.

AIM: Congenital hyperinsulinism (CHI) is a heterogeneous disease with variable genetic etiology, histopathology, and clinical phenotype. This study aims to describe the clinical characteristics of persistent CHI and evaluate long-term neurological outcome and its risk factors in a cohort of Egyptian children. METHODS: Clinical, genetic, and biochemical data of 42 patients with CHI were collected. Patients were invited for neurological assessment, electroencephalogram, and magnetic resonance imaging of the brain. RESULTS: ABCC8 mutation was found in (61%) of cases who underwent genetic testing (17/28). Five cases with homozygous biparental ABCC8 mutation responded to combined diazoxide and octreotide without needing surgery. Seven out of twenty-one patients who had pancreatectomy (33%) developed diabetes after a median period of 4.8 (range:1-10) years following surgery. Fifty-five percent of our patients had neurodevelopmental impairment at follow-up. Logistic regression analysis has shown that delayed referral to tertiary centre for more than 8 days, delayed diagnosis of CHI for more than 14 days and hospital admission for more than 30 days, are significant predictors of unfavorable neurological sequelae in CHI; (OR = 12.7 [2.56], p = 0.001), (OR = 12.7 [2.9-56], p = 0.001), and (OR = 3.8 [0.14.5], p = 0.043), respectively. CONCLUSIONS: ABCC8 mutation was the commonest genetic mutation underlying CHI in this study group. CHI cases with biparental homozygous ABCC8 mutation may show response to combined octreotide and diazoxide therapy. More than half of our patients had neurodevelopmental impairment at follow-up. Delayed referral to expert centre, delayed diagnosis and longer hospital stay are significant predictors of neurological disability in CHI cases.

Long-Term Outcome and Treatment in Persistent and Transient Congenital Hyperinsulinism: A Finnish Population-Based Study.

CONTEXT: The management of congenital hyperinsulinism (CHI) has improved. OBJECTIVE: To examine the treatment and long-term outcome of Finnish patients with persistent and transient CHI (P-CHI and T-CHI). DESIGN: A population-based retrospective study of CHI patients treated from 1972 to 2015. PATIENTS: 106 patients with P-CHI and 132 patients with T-CHI (in total, 42 diagnosed before and 196 after year 2000) with median follow-up durations of 12.5 and 6.2 years, respectively. MAIN OUTCOME MEASURES: Recovery, diabetes, pancreatic exocrine dysfunction, neurodevelopment. RESULTS: The overall incidence of CHI (n = 238) was 1:11 300 live births (1972-2015). From 2000 to 2015, the incidence of P-CHI (n = 69) was 1:13 500 and of T-CHI (n = 127) 1:7400 live births. In the 21st century P-CHI group, hyperinsulinemic medication was initiated and normoglycemia achieved faster relative to earlier. Of the 74 medically treated P-CHI patients, 68% had discontinued medication. Thirteen (12%) P-CHI patients had partial pancreatic resection and 19 (18%) underwent near-total pancreatectomy. Of these, 0% and 84% developed diabetes and 23% and 58% had clinical pancreatic exocrine dysfunction, respectively. Mild neurological difficulties (21% vs 16%, respectively) and intellectual disability (9% vs 5%, respectively) were as common in the P-CHI and T-CHI groups. However, the 21st century P-CHI patients had significantly more frequent normal neurodevelopment and significantly more infrequent diabetes and pancreatic exocrine dysfunction compared with those diagnosed earlier. CONCLUSIONS: Our results demonstrated improved treatment and long-term outcome in the 21st century P-CHI patients relative to earlier.

Congenital hyperinsulinism: characterization of patients treated in a pediatric university hospital in Colombia.

Background: Congenital hyperinsulinism is a disease of the glucose metabolism, relevant in pediatric endocrinology because of the elevated production of insulin according to blood glucose level, which leads to persistent severe hypoglycemia. This condition can produce important neurological sequelae in the patient due to the irreversible damage that occurs in the neuron caused by the exposure to hypoglycemia for short periods of time. Congenital hyperinsulinism diagnosis is not simple and it requires a high index of suspicion. The treatment should be established sequentially, in several steps, noticing the response to each possible medication used. If the pharmacological management fails, surgical procedures are required occasionally. Case series report: Seven cases of congenital hyperinsulinism diagnosed in the last seven years at the Instituto Roosevelt in Bogotá, Colombia are presented. In this country, the radiotracer used internationally during positron emission tomography/computed tomography (PET/CT) is not available. However, was possible to use an alternative radiotracer in one of the cases, which led to an adequate diagnosis and a successful surgical treatment. Conclusions: Congenital hyperinsulinism is a complex clinical condition, which requires proper diagnosis and treatment, with the aim of avoiding any neurological damage caused by persistent hypoglycemia. PET/CT can be used with an appropriate radiotracer for a timely diagnosis and to provide the best available therapeutic option.

Introducción: El hiperinsulinismo congénito es una enfermedad del metabolismo de la glucosa, fundamental en la endocrinología pediátrica, ya que se refiere a la producción de mayor cantidad de insulina de la necesaria según la glucemia, lo cual produce hipoglucemias graves persistentes. Esta alteración puede tener importantes secuelas neurológicas debido al daño irreversible que se produce en la neurona por la exposición a la hipoglucemia por cortos periodos de tiempo. Su diagnóstico no es sencillo y requiere un alto índice de sospecha. El tratamiento se establece de manera secuencial, en varias etapas, observando la respuesta a cada uno de los posibles medicamentos empleados. En caso de que falle el manejo farmacológico, se requieren procedimientos quirúrgicos. Serie de casos: Se presentan siete casos de hiperinsulinismo congénito que fueron diagnosticados en los últimos 7 años en el Instituto Roosevelt en Bogotá, Colombia. En este país, el radiotrazador empleado usualmente durante la tomografía por emisión de positrones (PET/TC) no se encuentra disponible. Sin embargo, en uno de los casos descritos fue posible emplear otro radiotrazador alternativo que permitió un adecuado diagnóstico y un tratamiento quirúrgico exitoso. Conclusiones: El hiperinsulinismo congénito es una condición clínica compleja que amerita un correcto diagnóstico y un apropiado manejo, con el objetivo de evitar el daño neurológico que producen las hipoglucemias persistentes. Es posible emplear PET/TC con un radiotrazador adecuado para realizar un diagnóstico oportuno y proporcionar la mejor opción terapéutica disponible.

Delayed Resolution of Feeding Problems in Patients With Congenital Hyperinsulinism.

Background: Congenital Hyperinsulinism (CHI) is the most common cause of recurrent and severe hypoglycaemia in childhood. Feeding problems occur frequently in severe CHI but long-term persistence and rates of resolution have not been described. Methods: All patients with CHI admitted to a specialist center during 2015-2016 were assessed for feeding problems at hospital admission and for three years following discharge, through a combination of specialist speech and language therapy review and parent-report at clinical contact. Results: Twenty-five patients (18% of all patients admitted) with CHI were prospectively identified to have feeding problems related to sucking (n = 6), swallowing (n = 2), vomiting (n = 20), and feed aversion (n = 17) at the time of diagnosis. Sixteen (64%) patients required feeding support by nasogastric/gastrostomy tubes at diagnosis; tube feeding reduced to 4 (16%) patients by one year and 3 (12%) patients by three years. Feed aversion resolved slowly with mean time to resolution of 240 days after discharge; in 15 patients followed up for three years, 6 (24%) continued to report aversion. The mean time (days) to resolution of feeding problems was lower in those who underwent lesionectomy (n = 4) than in those who did not (30 vs. 590, p = 0.009) and significance persisted after adjustment for associated factors (p = 0.015). Conclusion: Feeding problems, particularly feed aversion, are frequent in patients with CHI and require support over several years. By contrast, feeding problems resolve rapidly in patients with focal CHI undergoing curative lesionectomy, suggesting the association of feeding problems with hyperinsulinism.

Hiperinsulinismo congénito: caracterización de pacientes atendidos en un hospital universitario pediátrico en Colombia / Congenital hyperinsulinism: characterization of patients treated in a pediatric university hospital in Colombia

Resumen Introducción: El hiperinsulinismo congénito es una enfermedad del metabolismo de la glucosa, fundamental en la endocrinología pediátrica, ya que se refiere a la producción de mayor cantidad de insulina de la necesaria según la glucemia, lo cual produce hipoglucemias graves persistentes. Esta alteración puede tener importantes secuelas neurológicas debido al daño irreversible que se produce en la neurona por la exposición a la hipoglucemia por cortos periodos de tiempo. Su diagnóstico no es sencillo y requiere un alto índice de sospecha. El tratamiento se establece de manera secuencial, en varias etapas, observando la respuesta a cada uno de los posibles medicamentos empleados. En caso de que falle el manejo farmacológico, se requieren procedimientos quirúrgicos. Serie de casos: Se presentan siete casos de hiperinsulinismo congénito que fueron diagnosticados en los últimos 7 años en el Instituto Roosevelt en Bogotá, Colombia. En este país, el radiotrazador empleado usualmente durante la tomografía por emisión de positrones (PET/TC) no se encuentra disponible. Sin embargo, en uno de los casos descritos fue posible emplear otro radiotrazador alternativo que permitió un adecuado diagnóstico y un tratamiento quirúrgico exitoso. Conclusiones: El hiperinsulinismo congénito es una condición clínica compleja que amerita un correcto diagnóstico y un apropiado manejo, con el objetivo de evitar el daño neurológico que producen las hipoglucemias persistentes. Es posible emplear PET/TC con un radiotrazador adecuado para realizar un diagnóstico oportuno y proporcionar la mejor opción terapéutica disponible.

Abstract Background: Congenital hyperinsulinism is a disease of the glucose metabolism, relevant in pediatric endocrinology because of the elevated production of insulin according to blood glucose level, which leads to persistent severe hypoglycemia. This condition can produce important neurological sequelae in the patient due to the irreversible damage that occurs in the neuron caused by the exposure to hypoglycemia for short periods of time. Congenital hyperinsulinism diagnosis is not simple and it requires a high index of suspicion. The treatment should be established sequentially, in several steps, noticing the response to each possible medication used. If the pharmacological management fails, surgical procedures are required occasionally. Case series report: Seven cases of congenital hyperinsulinism diagnosed in the last seven years at the Instituto Roosevelt in Bogotá, Colombia are presented. In this country, the radiotracer used internationally during positron emission tomography/computed tomography (PET/CT) is not available. However, was possible to use an alternative radiotracer in one of the cases, which led to an adequate diagnosis and a successful surgical treatment. Conclusions: Congenital hyperinsulinism is a complex clinical condition, which requires proper diagnosis and treatment, with the aim of avoiding any neurological damage caused by persistent hypoglycemia. PET/CT can be used with an appropriate radiotracer for a timely diagnosis and to provide the best available therapeutic option.

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management.

Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-18 dihydroxyphenylalanine-positron emission tomography. Newer and improved isotopes are currently in development to provide increased diagnostic accuracy in identifying lesions and performing successful surgical resection with the ultimate aim of curing the condition. Rapid diagnostics and innovative methods of management, including a wider range of treatment options, have resulted in a reduction in co-morbidities associated with HH with improved quality of life and long-term outcomes. Potential future developments in the management of this condition as well as pathways to transition of the care of these highly vulnerable children into adulthood will also be discussed.