Management and Appropriate Use of Diazoxide in Infants and Children with Hyperinsulinism

Abstract

Background The diagnosis of hypoglycemia and the use of diazoxide have risen in the last decade. Diazoxide is the only FDA-approved pharmacologic treatment for neonatal hypoglycemia caused by hyperinsulinism (HI). Recent publications have highlighted that diazoxide has serious adverse effects (AEs) such as pulmonary hypertension (2-3%) and neutropenia (15%). Despite its increasing use, there is little information regarding dosing of diazoxide and/or monitoring for AEs. Methods We convened a working group of pediatric endocrinologists who were members of the Drug and Therapeutics Committee of the Pediatric Endocrine Society (PES) to review the available literature. Our Committee sent a survey to its PES members regarding the use of diazoxide in their endocrine practices. Our review of the results concluded that there was substantial heterogeneity in usage and monitoring for AEs for diazoxide among pediatric endocrinologists. Conclusions Based on our extensive literature review and on the lack of consensus regarding use of diazoxide noted in our PES survey, our group graded the evidence using the framework of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group, and has proposed expert consensus practice guidelines for the appropriate use of diazoxide in infants and children with HI. We summarized information on AEs reported to date and have provided practical ideas for dosing and monitoring for AEs in infants treated with diazoxide.

Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation

“…Diazoxide, the first line treatment of congenital HH, binds to the linker region of the SUR1 subunit of the KATP channels and suppresses β-cell insulin secretion by forcing the channels to remain open [20]. Early diazoxide administration was a solid judgment for our patient during HH events, even prior to genetic diagnosis.…”

Novel KDM6A Kabuki Syndrome Mutation With Hyperinsulinemic Hypoglycemia and Pulmonary Hypertension Requiring ECMO

“…Another study demonstrated a much lower risk for severe adverse events (SAE) including PH associated with diazoxide use in those with genetic HH (3.6% with any SAE, 1.2% with PH) as compared to those with perinatal stress hyperinsulinism (16.7% with any SAE, 7.6% with PH) [ 17 ]. Currently, there is limited evidence on diazoxide dosing strategies, but the expert consensus of the members of the Drug and Therapeutics Committee of the Pediatric Endocrine Society emphasized the importance of reducing diazoxide dose if hyperglycemia occurs [ 18 ]. It thus remains unclear in our patient to what extent the low dose of diazoxide may have contributed to her decompensation, which was very likely primarily related to her underlying cardiopulmonary pathology.…”

Asymptomatic Hyperinsulinemic Hypoglycemia and Grade 4 Intraventricular Hemorrhage in a Late Preterm Infant

“… 28 A normal hepatic and renal function tests and cardiac evaluation before diazoxide initiation are prerequisites to avoid complications. 29 …”

“…28 A normal hepatic and renal function tests and cardiac evaluation before diazoxide initiation are prerequisites to avoid complications. 29 Regular follow-up appointments continue with neonatologist, endocrinologist, neurologist, and neurosurgeon. Diazoxide was allowed to self-wean with weight gain.…”