International Guidelines for the Diagnosis and Management of Hyperinsulinism
Pediatric Endocrine Society/ESPE/interna… · 2023 · international
Source and licence
- Authors
- Diva D De Leon, Jean Baptiste Arnoux, Indraneel Banerjee et al.
- Title
- International Guidelines for the Diagnosis and Management of Hyperinsulinism
- Journal
- Hormone research in paediatrics, 2023
- Licence
- CC BY 4.0
- Changes
- Verbatim excerpts; formatting adapted
Full text retrieved 2026-10-27 from Europe PMC · PMC11124746
Licence statement of the original publication
This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY) (http://www.karger.com/Services/OpenAccessLicense). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.
This page reproduces excerpts of the original publication; the original is authoritative. It has not been reviewed by a physician, does not state a recommendation of Medelix and does not replace medical advice. The guideline may have been updated since.
Open the original publication →Full text on Europe PMC
Recommendations
Verbatim, with grade of recommendation or strength of consensus where given.
We Recommend Making a Specific Diagnosis of Hyperinsulinism Based on Measurements, at a Time of Hypoglycemia, of Plasma Levels of Metabolic Fuels (Beta-Hydroxybutyrate [BOHB] and Free Fatty Acids [FFA]) and Hormones (Insulin, Growth Hormone, Cortisol) and Determination of the Glycemic Response to a Pharmacologic Dose of Glucagon [Grade 1 ⊕⊕⊕○]
- 1.2 We Recommend Genetic Testing for all Children except for Those Likely to Have an Acquired Form of HyperinsulinismGRADE 1⊕⊕⊕○
- 1.3 We Recommend Evaluation of Infants with Hyperinsulinism for Multi-System Syndromes Associated with HyperinsulinismGRADE 1⊕⊕○○
Surgical Management
- 3.1 We Recommend that Surgery Be Considered for Children Suspected to Have a Resectable Focal LesionGRADE 1⊕⊕⊕○
Abstract
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. Rapid turnaround of genetic test results combined with advanced radiologic imaging can permit identification and localization of surgically-curable focal lesions in a large proportion of children with congenital forms of HI, but are only available in certain centers in “developed” countries. Diazoxide, the only drug currently approved for treating HI, was recently designated as an “essential medicine” by the World Health Organization but has been approved in only 16% of Latin American countries and remains unavailable in many underdeveloped areas of the world. Novel treatments for HI are emerging, but they await completion of safety and efficacy trials before being considered for clinical use.
Key Messages: This international consensus statement on diagnosis and management of HI was developed in order to assist specialists, general pediatricians, and neonatologists in early recognition and treatment of HI with the ultimate aim of reducing the prevalence of brain injury caused by hypoglycemia. A previous statement on diagnosis and management of HI in Japan was published in 2017. The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited.
Contents of the original publication
The section headings of the original.
- Method of Development of Evidence-Based Clinical Practice Guidelines
- The Diagnosis of Hyperinsulinism
- We Recommend Making a Specific Diagnosis of Hyperinsulinism Based on Measurements, at a Time of Hypoglycemia, of Plasma Levels of Metabolic Fuels (Beta-Hydroxybutyrate [BOHB] and Free Fatty Acids [FFA]) and Hormones (Insulin, Growth Hormone, Cortisol) and Determination of the Glycemic Response to a Pharmacologic Dose of Glucagon [Grade 1 ⊕⊕⊕○]
- We Recommend Screening all Children Whose Hyperinsulinism Occurs after the Age of 2 years of Life for Insulinoma [Grade 1⊕⊕○○]
- We Recommend that Pancreatic Imaging Studies (e.g., 18F-DOPA PET Scan) to Localize a Potentially Resectable Focal Lesion Be Performed in Infants with Diazoxide-Unresponsive Hyperinsulinism, except in Those with Genetic Evidence of Diffuse Disease [GRADE 1 ⊕⊕⊕○]
- Medical Management
- We Recommend that the Goal of Treatment for Hyperinsulinism Is to Maintain Plasma Glucose Concentrations within the Normal Range of 70–100 mg/dL (3.9–5.6 mmol/L) [Grade 1⊕⊕○○]
- We Recommend that Intravenous Glucose (Dextrose) Infusion Be Used as the Initial Treatment to Promptly Restore Euglycaemia for Neonates with Hyperinsulinism [Grade 1 ⊕⊕⊕○]
- We Recommend Continuous Intravenous Infusion of Glucagon for Infants at Risk of Fluid Overload because of a High Glucose Requirement [Grade 1⊕⊕○○]
- We Recommend Diazoxide as the First-Line Treatment for Patients with an Established Diagnosis of Hyperinsulinism [Grade 1⊕⊕⊕○]
- We Suggest the Use of Somatostatin Analogues as Second-Line Treatment for Infants with Hyperinsulinism Who Are Diazoxide-Unresponsive or Have Unacceptable Diazoxide Side Effects or Are Unable to Obtain Diazoxide [Grade 2⊕⊕○○]
- We Suggest that Medications Which Lack Adequate Proof of Efficacy (i.e., Nifedipine, Sirolimus, etc.) Not Be Used to Treat Hyperinsulinism unless Part of an Approved Investigational Protocol [Grade 2⊕⊕○○]
- We Suggest Carbohydrate Supplementation to Maintain Euglycaemia in Infants and Children with Hyperinsulinism Who Are Not Adequately Controlled on Pharmacologic Therapy Alone [Grade 2⊕⊕○○]
- Surgical Management
- We Suggest that Infants with Hyperinsulinism due to Diffuse Pancreatic Disease Should Undergo Surgery if Hypoglycemia Is Not Adequately Controlled despite Maximal Medical Therapy [GRADE 2⊕⊕○○]
- Discharge Planning
- We Suggest that Discharge Planning for Children with Hyperinsulinism Include an Assessment of Fasting Tolerance [GRADE 2⊕⊕○○]
- Long-Term Management of Patients with Hyperinsulinism
- We Suggest Regular Follow-Up and Monitoring to Assess Glycemic Control, Medication Side Effects, and the Development of Diabetes or Pancreatic Insufficiency [Grade 2⊕⊕⊕○]
- We Recommend that, due to the Increased Risk of Neurocognitive Deficits and Feeding Difficulties, All Children with Hyperinsulinism Should Undergo a Referral for Developmental Surveillance, Feeding Assessment, and Early Intervention [GRADE 1⊕⊕⊕○]
- We Suggest that Programs Be Established for the Transition to Adult Care for Children and Adolescents with Hyperinsulinism and Ongoing Medical Needs, and for the Development of Adult Programs for Adults with Hyperinsulinism [Grade 2⊕⊕○○]
- Conclusions
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