Development of Pulmonary Hypertension During Treatment with Diazoxide: A Case Series and Literature Review

Pediatr Cardiol. 2017 Aug;38(6):1247-1250. doi: 10.1007/s00246-017-1652-3. Epub 2017 Jun 22.

Abstract

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy. The mainstay of medical management for CHI is diazoxide. Diazoxide inhibits insulin release from the pancreas, but also causes smooth muscle relaxation and fluid retention so it is typically given with chlorothiazide. In July 2015, the FDA issued a drug safety communication warning that pulmonary hypertension (PH) had been reported in 11 infants being treated with diazoxide and that the PH resolved with withdrawal of diazoxide. All three of the cases in our hospital were admitted to the neonatal intensive care unit (NICU) for hypoglycemia. All patients received thorough radiologic and laboratory evaluations related to their diagnosis of CHI. All initially improved when diazoxide was initiated. Case 1 and case 3 were discharged from the NICU on diazoxide and chlorothiazide. Case 2 developed pulmonary hypertension while still in the NICU days after an increase in diazoxide dosing. Case 1 presented to the emergency room in respiratory distress shortly after discharge from the NICU with evidence of PH and heart failure. Case 3 presented to the emergency room after 2 weeks at home due to a home blood glucose reading that was low and developed PH and heart failure while an inpatient. Discontinuation of diazoxide led to resolution of all three patients' PH within approximately one week. The experience of our hospital indicates that pulmonary hypertension may be more common than previously thought in infants taking diazoxide. It is unclear if these symptoms develop slowly over time or if there is some other, as yet undescribed, trigger for the pulmonary hypertension. Our hospital's experience adds to the body of evidence and suggests these infants may benefit from more surveillance with echocardiography.

Keywords: Circulatory overload; Congenital hyperinsulinism; Diazoxide; Pulmonary hypertension.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Congenital Hyperinsulinism / drug therapy*
  • Diazoxide / adverse effects*
  • Diazoxide / therapeutic use
  • Humans
  • Hypertension, Pulmonary / chemically induced*
  • Hypertension, Pulmonary / diagnosis
  • Infant, Newborn
  • Insulin Antagonists / adverse effects*
  • Insulin Antagonists / therapeutic use
  • Male

Substances

  • Insulin Antagonists
  • Diazoxide