Adverse Events Associated With Diazoxide Treatment for Congenital Hyperinsulinism
Careful surveillance for more common adverse effects including neutropenia, thrombocytopenia, and hyperuricemia is warranted in children treated with diazoxide.
According to a study published in the Journal of Clinical Endocrinology & Metabolism, diazoxide treatment in children and infants with congenital hyperinsulinism is associated most commonly with neutropenia, but there is also a slight risk for pulmonary hypertension.
Researchers conducted this retrospective cohort study to determine the frequency of and clinical factors associated with adverse events in infants and children prescribed diazoxide for hyperinsulinism. Included in the study were 295 patients (median age at diazoxide initiation, 29 days) diagnosed with hyperinsulinism and treated between 2003 and 2014 with a maximum diazoxide dose of 15 mg/kg/day.
Among patients who discontinued diazoxide treatment during follow-up (n = 137), median duration of drug use was 48 days. There were 6 patients who died during follow-up, 3 of whom were receiving diazoxide at time of death. None of these patients had documented pulmonary hypertension.
Of all patients who underwent diazoxide treatment, 2.4% demonstrated echocardiographic evidence of pulmonary hypertension, which researchers concluded might be associated with delayed diuretic initiation. These infants had higher rates of prematurity and were significantly more likely to have had edema during or shortly after diazoxide treatment (P =.04). Participants were also likely to have had higher baseline risk as a result of underlying developmental or congenital abnormalities such as respiratory failure, structural heart disease, and other factors associated with pulmonary hypertension.
Other adverse events occurred at a higher rate, with 15.6% of patients developing neutropenia, 4.7% developing thrombocytopenia, and 5.0% developing hyperuricemia.
Certain limitations were noted for this study, including the possibility that cases of mild pulmonary hypertension without clinical manifestation were missed as a result of lack of screening echocardiography in all patients.
"Diazoxide is typically a safe, effective therapy for patients with [hyperinsulinism], but careful surveillance for more common adverse effects including neutropenia, thrombocytopenia and hyperuricemia is warranted," stated the researchers. "[Pulmonary hypertension] may be more common among premature infants, as well as patients with baseline cardiac or pulmonary disease."
Herrera A, Vajravelu ME, Givler S, et al. Prevalence of adverse events in children with congenital hyperinsulinism treated with diazoxide [published online September 21, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01613