Dasiglucagon in Children with Congenital Hyperinsulinism up to 1 Year of Age: Results from a Randomized Clinical Trial.

Context: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia in childhood with considerable risk of lifelong neurological sequelae. Available pharmacological therapies are limited. Dasiglucagon is a glucagon analog for the treatment of hypoglycemia.

An auto-ethnographic study of co-produced health research in a patient organisation: unpacking the good, the bad, and the unspoken.

Background: In rare diseases, limited access to services and rare disease experts may force families to act as medical advocates for their child; they can volunteer to support clinician-initiated research or initiate and lead research themselves. Ketotic Hypoglycemia International (KHI) is a new, global organization for families affected by idiopathic ketotic hypoglycemia (IKH) and is run solely by volunteers. Doing research together, families and international experts in a collaborative process such as at KHI, also referred to as patient and public involvement and engagement (PPIE) or extreme citizen science, is often praised for its positive effects on the research and the stakeholders involved.

The Birth Prevalence of Congenital Hyperinsulinism: A Narrative Review of the Epidemiology of a Rare Disease.

Background: Congenital hyperinsulinism (HI) is a rare pediatric disease and the most common cause of severe, persistent hypoglycemia in childhood. It is characterized by the dysregulation of insulin secretion from the pancreas and can lead to irreversible brain damage with lifelong neurodisability.

Summary: The global birth prevalence of HI is currently unknown.

The Production of Polysarcosine-Containing Nanoparticles by Ring-Opening Polymerization-Induced Self-Assembly.

N-carboxyanhydride ring-opening polymerization-induced self-assembly (NCA ROPISA) offers a convenient route for generating poly(amino acid)-based nanoparticles in a single step, crucially avoiding the need for post-polymerization self-assembly. Most examples of NCA ROPISA make use of a poly(ethylene glycol) (PEG) hydrophilic stabilizing block, however this non-biodegradable, oil-derived polymer may cause an immunological response in some individuals. Alternative water-soluble polymers are therefore highly sought.

Idiopathic Pathological Ketotic Hypoglycemia: Finding the Needle in a Haystack.

Sick children often have a decreased appetite and experience vomiting and diarrhea; however, hypoglycemia (plasma glucose concentration ≤50 mg/dL or 2.8 mmol/L) is rare. Ketotic hypoglycemia (KH) is the most common cause of hypoglycemia presenting to an Emergency Department in a previously healthy child between 6 months and 6 years of age.

Approach to the Patient: Investigation of Pediatric Hypoglycemia in the Emergency Department-A Practical Algorithm.

Hypoglycemia in the pediatric population tends to present in the newborn period or during metabolic crisis triggered by prolonged fasting and intercurrent illness. Current recommendations to investigate all children presenting with hypoglycemia for the first time are cumbersome and costly but necessary to identify those with serious conditions who predispose to hypoglycemia. We describe a practical and cost-effective method of evaluating children who present to the emergency department with previously undiagnosed hypoglycemia.

Practice Variation among Pediatric Endocrinologists in the Dosing of Glucocorticoids in Young Children with Congenital Adrenal Hyperplasia.

A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.

Dasiglucagon for the Treatment of Congenital Hyperinsulinism: A Randomized Phase 3 Trial in Infants and Children.

Context: Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion causing hypoglycemia and consequent brain damage. Dasiglucagon is a glucagon analogue under investigation to treat CHI.

Objective: To evaluate the efficacy and safety of dasiglucagon delivered via continuous subcutaneous infusion to children with CHI and persistent hypoglycemia as add-on to standard of care (SoC).

International Guidelines for the Diagnosis and Management of Hyperinsulinism.

Background: Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI; however, there have been almost no new therapeutic modalities since the development of diazoxide.

Summary: Recent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism.

New approaches to screening and management of neonatal hypoglycemia based on improved understanding of the molecular mechanism of hypoglycemia.

For the past 70 years, controversy about hypoglycemia in newborn infants has focused on a numerical "definition of neonatal hypoglycemia", without regard to its mechanism. This ignores the purpose of screening newborns for hypoglycemia, which is to identify those with pathological forms of hypoglycemia and to prevent hypoglycemic brain injury. Recent clinical and basic research indicates that the three major forms of neonatal hypoglycemia are caused by hyperinsulinism (recognizing also that other rare hormonal or metabolic conditions may also present during this time frame).

Congenital Hyperinsulinism: An Historical Perspective.

Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates, infants, and children. Since the first case descriptions in the 1950s, the field has advanced significantly. It was the development of the insulin radioimmunoassay by Yalow and Berson a decade later that made it possible to demonstrate that this form of persistent hypoglycemia was caused by insulin, and a few years later, Drash described the successful treatment of children with hyperinsulinism with the antihypertensive diazoxide, which until today remains the only approved treatment for hyperinsulinism.

Hyperinsulinemic Hypoglycemia Associated with a Ca1.2 Variant with Mixed Gain- and Loss-of-Function Effects.

The voltage-dependent L-type calcium channel isoform Ca1.2 is critically involved in many physiological processes, e.g.

Safety and Efficacy of Lonapegsomatropin in Children With Growth Hormone Deficiency: enliGHten Trial 2-Year Results.

Purpose: The objectives of the ongoing, Phase 3, open-label extension trial enliGHten are to assess the long-term safety and efficacy of weekly administered long-acting growth hormone lonapegsomatropin in children with growth hormone deficiency.

Methods: Eligible subjects completing a prior Phase 3 lonapegsomatropin parent trial (heiGHt or fliGHt) were invited to participate. All subjects were treated with lonapegsomatropin.

Switching to Weekly Lonapegsomatropin from Daily Somatropin in Children with Growth Hormone Deficiency: The fliGHt Trial.

Introduction: The phase 3 fliGHt Trial evaluated the safety and tolerability of once-weekly lonapegsomatropin, a long-acting prodrug, in children with growth hormone deficiency (GHD) who switched from daily somatropin therapy to lonapegsomatropin.

Methods: This multicenter, open-label, 26-week phase 3 trial took place at 28 sites across 4 countries (Australia, Canada, New Zealand, and the USA). The trial enrolled 146 children with GHD, 143 of which were previously treated with daily somatropin.

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.

Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial.

Context: For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD.

Objective: The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin.

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.

Towards enhanced understanding of idiopathic ketotic hypoglycemia: a literature review and introduction of the patient organization, Ketotic Hypoglycemia International.

Background: Idiopathic Ketotic hypoglycemia (IKH) is a diagnosis of exclusion. Although considered as the most frequent cause of hypoglycemia in childhood, little progress has been made to advance the understanding of IKH since the medical term was coined in 1964. We aimed to review the literature on ketotic hypoglycemia (KH) and introduce a novel patient organization, Ketotic Hypoglycemia International (KHI).

Brain MRIs may be of low value in most children diagnosed with isolated growth hormone deficiency.

Objectives: Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormone deficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7-10 ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations.

Methods: In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed.