Prevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide.

TitlePrevalence of Adverse Events in Children With Congenital Hyperinsulinism Treated With Diazoxide.
Publication TypeJournal Article
Year of Publication2018
AuthorsHerrera A, Vajravelu MEllen, Givler S, Mitteer L, Avitabile CM, Lord K, De León DD
JournalJ Clin Endocrinol Metab
Volume103
Issue12
Pagination4365-4372
Date Published2018 Dec 01
ISSN1945-7197
Abstract

Context: Diazoxide, the only U.S. Food and Drug Administration-approved drug to treat hyperinsulinemic hypoglycemia, has been associated with several adverse events, which has raised concerns about the safety of this drug. Existing reports are limited to small studies and case reports.

Objective: To determine prevalence of and clinical factors associated with adverse events in infants and children treated with diazoxide.

Design: Retrospective cohort study of children with hyperinsulinism (HI) treated with diazoxide between 2003 and 2014.

Setting: The Congenital Hyperinsulinism Center at the Children's Hospital of Philadelphia.

Patients: Children and infants with laboratory-confirmed diagnosis of HI.

Main Outcome Measures: Prevalence of pulmonary hypertension (PH), edema, neutropenia, thrombocytopenia, and hyperuricemia was determined. Tests of association and logistic regression were used to identify potential risk factors.

Results: A total of 295 patients (129 female) met inclusion criteria. The median age at diazoxide initiation was 29 days (interquartile range, 10 to 142 days; n = 226 available start dates); 2.4% of patients were diagnosed with PH after diazoxide initiation. Children with PH (P = 0.003) or edema (P = 0.002) were born at earlier gestational age and more frequently had potential PH risk factors, including respiratory failure and structural heart disease (P < 0.0001 and P = 0.005). Other adverse events included neutropenia (15.6%), thrombocytopenia (4.7%), and hyperuricemia (5.0%).

Conclusion: In this large cohort, PH occurred in infants with underlying risk factors, but no identifiable risk profile emerged for other adverse events. The relatively high prevalence of neutropenia, thrombocytopenia, and hyperuricemia suggests the value in proactively screening for these side effects in children treated with diazoxide.

DOI10.1210/jc.2018-01613
Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID30247666
PubMed Central IDPMC6207144
Grant ListK12 DK094723 / DK / NIDDK NIH HHS / United States
R01 DK098517 / DK / NIDDK NIH HHS / United States
T32 DK007314 / DK / NIDDK NIH HHS / United States