Elsevier

The Journal of Pediatrics

Volume 148, Issue 2, February 2006, Pages 207-212
The Journal of Pediatrics

Original article
Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism

Presented in part at the Pediatric Academic Societies Meeting, Seattle, Washington, May 2003.
https://doi.org/10.1016/j.jpeds.2005.10.002Get rights and content

Objectives

To characterize the clinical features and insulin regulation in infants with hypoglycemia due to prolonged neonatal hyperinsulinism.

Study design

Data were collected on 26 infants with hypoglycemia due to neonatal hyperinsulinism that later resolved. Acute insulin response (AIR) tests to calcium, leucine, glucose, and tolbutamide were performed in 11 neonates. Results were compared to children with genetic hyperinsulinism due to mutations of the adenosine triphosphate–dependent potassium (KATP) channel and glutamate dehydrogenase (GDH).

Results

Among the 26 neonates, there were significantly more males, small-for-gestational-age infants, and cesarean deliveries. Only 5 of the 26 had no identifiable risk factor. Hyperinsulinism was diagnosed at a median age of 13 days (range, 2 to 180 days) and resolved by a median age of 181 days (range, 18 to 403 days). Diazoxide was effective in 19 of the 21 neonates treated. In the 11 neonates tested, the AIRs to calcium, leucine, glucose, and tolbutamide resembled those in normal controls and differed from genetic hyperinsulinism due to KATP channel and GDH mutations.

Conclusions

We define a syndrome of prolonged neonatal hyperinsulinism that is responsive to diazoxide, persists for several months, and resolves spontaneously. AIR tests suggest that both the KATP channel and GDH have normal function.

Section snippets

Methods

Between 1999 and 2002, data were prospectively collected from all neonates admitted to the Neonatal Intensive Care Unit at Children’s Hospital of Philadelphia who were referred to the Division of Endocrinology for hypoglycemia due to suspected hyperinsulinism. Those neonates with hyperinsulinism that subsequently spontaneously resolved were diagnosed with prolonged neonatal hyperinsulinism. After excluding infants of diabetic mothers and neonates with permanent genetic forms of hyperinsulinism

Clinical characteristics

Table I summarizes the clinical features of the 26 neonates with prolonged neonatal hyperinsulinism. All were born within 100 miles of Philadelphia. Compared with the reference newborn population, there was a significant excess of males, SGA newborns, and cesarean deliveries. Thirty-five percent of the neonates had signs of perinatal stress (including metabolic acidosis and/or abnormal fetal tracing) suggesting birth asphyxia, although none had a 5-minute APGAR score below 6. Prematurity and

Discussion

The results of the present study define a group of neonates who have hypoglycemia persisting for several weeks to months after birth as the result of a prolonged form of hyperinsulinism that eventually resolves completely. This prolonged neonatal hyperinsulinism syndrome is frequently associated with male sex, low birth weight, perinatal stress, and cesarean delivery. In contrast to children with severe neonatal-onset hyperinsulinism associated with KATP mutations, neonates with prolonged

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    Supported in part by a research fellowship award from the Juvenile Diabetes Research Foundation (F.M.H.), National Institutes of Health grant R01 DK56268 (C.A.S.), and General Clinical Research Center grant M01 RR00240.

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