Low-dose diazoxide is safe and effective in infants with transient hyperinsulinism.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Blackwell Publishing Country of Publication: England NLM ID: 0346653 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2265 (Electronic) Linking ISSN: 03000664 NLM ISO Abbreviation: Clin Endocrinol (Oxf) Subsets: MEDLINE
    • Publication Information:
      Publication: <2003->: Oxford : Blackwell Publishing
      Original Publication: Oxford, Blackwell Scientific Publications.
    • Subject Terms:
      Hypoglycemia*/drug therapy ; Hyperinsulinism*/drug therapy ; Congenital Hyperinsulinism*/drug therapy; Infant ; Female ; Infant, Newborn ; Humans ; Male ; Diazoxide/adverse effects ; Infant, Small for Gestational Age ; Risk Factors
    • Abstract:
      Objective: Transient hyperinsulinism (THI) is the most common form of recurrent hypoglycaemia in neonates beyond the first week of life. Although self-resolving, treatment can be required. Consensus guidelines recommend the lower end of the diazoxide 5-15 mg/kg/day range in THI to reduce the risk of adverse events. We sought to determine if doses <5 mg/kg/day of diazoxide can be effective in THI.
      Design, Patients, Measurments: Infants with THI (duration <6 months) were treated with low-dose diazoxide from October 2015 to February 2021. Dosing was based on weight at diazoxide start: 2 mg/kg/day in infants 1000-2000 g (cohort 1), 3 mg/kg/day in those 2000-3500 g (cohort 2) and 5 mg/kg/day in those >3500 g.
      Results: A total of 73 infants with THI (77% male, 33% preterm, 52% small-for-gestational age) were commenced on diazoxide at a median age of 11 days (range 3-43) for a median duration of 4 months (0.3-6.8), with no difference between cohorts. The mean effective diazoxide dose was 3 mg/kg/day (range 1.5-10); 35% (26/73) required an increase from their starting dose, including 60% (9/15) of cohort 1. There was no association between perinatal stress risk factors or treatment-related characteristics and dose increase. Adverse events occurred in 13 patients (18%); oedema (12%) and hyponatraemia (5%) were the most common. Two infants developed suspected necrotising enterocolitis (NEC); none had pulmonary hypertension.
      Conclusion: Diazoxide doses <5 mg/kg/day are effective in THI. While the nature of the association between diazoxide and NEC was unclear, other adverse events were mild. We suggest considering starting doses as low as 2-3 mg/kg/day in THI to balance the side effect risk while maintaining euglycaemia.
      (© 2023 John Wiley & Sons Ltd.)
    • References:
      Güemes M, Hussain K. Hyperinsulinemic hypoglycemia. Pediatr Clin North Am. 2015;62:1017-1036. doi:10.1016/j.pcl.2015.04.010.
      Brar PC, Heksch R, Cossen K, et al. Management and appropriate use of diazoxide in infants and children with hyperinsulinism. J Clin Endocrinol Metab. 2020;105(12):3750-3761. doi:10.1210/clinem/dgaa543.
      Hoe FM, Thornton PS, Wanner LA, Steinkrauss L, Simmons RA, Stanley CA. Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism. J Pediatr. 2006;148(2):207-212. doi:10.1016/j.jpeds.2005.10.002.
      Raisingani M, Brar PC. Characterization of the duration of treatment with diazoxide in infants with prolonged hyperinsulinism (PHI). J Pediatr Endocrinol Metab. 2019;32(11):1241-1245. doi:10.1515/jpem-2019-0066.
      Davidov AS, Elkon-Tamir E, Haham A, et al. Higher c-peptide levels and glucose requirements may identify neonates with transient hyperinsulinism hypoglycemia who will benefit from diazoxide treatment. Eur J Pediatr. 2020;179(4):597-602. doi:10.1007/s00431-019-03544-z.
      Banerjee I, Salomon-Estebanez M, Shah P, Nicholson J, Cosgrove KE, Dunne MJ. Therapies and outcomes of congenital hyperinsulinism-induced hypoglycaemia. Diabetic Med. 2019;36(1):9-21. doi:10.1111/dme.13823.
      Herrera A, Vajravelu ME, Givler S, et al. Prevalence of adverse events in children with congenital hyperinsulinism treated with diazoxide. J Clin Endocrinol Metab. 2018;103(12):4365-4372. doi:10.1210/jc.2018-01613.
      Chen SC, Dastamani A, Pintus D, et al. Diazoxide-induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: recommendations from a multicentre study in the United Kingdom. Clin Endocrinol. 2019;91(6):770-775. doi:10.1111/cen.14096.
      Thornton P, Truong L, Reynolds C, Hamby T, Nedrelow J. Rate of serious adverse events associated with diazoxide treatment of patients with hyperinsulinism. Horm Res Paediatr. 2019;91(1):25-32. doi:10.1159/000497458.
      Prado LA, Castro M, Weisz DE, Jain A, Belik J. Necrotising enterocolitis in newborns receiving diazoxide. Arch Dis Child Fetal Neonatal Ed. 2021;106(3):306-310. doi:10.1136/archdischild-2020-319057.
      Keyes ML, Healy H, Sparger KA, et al. Necrotizing enterocolitis in neonates with hyperinsulinemic hypoglycemia treated with diazoxide. Pediatrics. 2021;147(2):e20193202. doi:10.1542/peds.2019-3202.
      Chen X, Feng L, Yao H, Yang L, Qin Y. Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: a systematic review and meta-analysis. PLoS One. 2021;16(2):e0246463. doi:10.1371/journal.pone.0246463.
      Desai J, Key L, Swindall A, Gaston K, Talati AJ. The danger of diazoxide in the neonatal intensive care unit. Ther Adv Drug Saf. 2021;12:20420986211011338. doi:10.1177/20420986211011338.
      Newman-Lindsay S, Lakshminrusimha S, Sankaran D. Diazoxide for neonatal hyperinsulinemic hypoglycemia and pulmonary hypertension. Children. 2022;10(1):5. doi:10.3390/children10010005.
      Duggal M, Moore SS, Simoneau J, et al. Pulmonary hypertension and necrotizing enterocolitis in neonates treated with diazoxide. Am J Perinatol. 2023. doi:10.1055/s-0043-1764385.
      Chandran S, R PR, Mei Chien C, Saffari SE, Rajadurai VS, Yap F. Safety and efficacy of low-dose diazoxide in small-for-gestational-age infants with hyperinsulinaemic hypoglycaemia. Arch Dis Child Fetal Neonatal Ed. 2022;107(4):359-363. doi:10.1136/archdischild-2021-322845.
      Guftar S, Lucas-Herald A, Dastamani A, et al. Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus. Front Endocrinol. 2023. doi:10.3389/fendo.2023.1231043.
      Fukutomi M, Shimodera M, Maeda Y, Iwakura M, Hara M. Safety and effectiveness, including intelligence prognosis, of diazoxide in pediatric patients with hyperinsulinemic hypoglycemia: special survey in Japan (long-term, all-case survey). Clin Pediatr Endocrinol. 2018;27(3):131-143. doi:10.1297/cpe.27.131.
      Balachandran B, Mukhopadhyay K, Sachdeva N, Walia R, Attri SV. Randomised controlled trial of diazoxide for small for gestational age neonates with hyperinsulinaemic hypoglycaemia provided early hypoglycaemic control without adverse effects. Acta Paediatr (Stockholm). 2018;107(6):990-995. doi:10.1111/apa.14252.
      Gray KD, Dudash K, Escobar C, et al. Prevalence and safety of diazoxide in the neonatal intensive care unit. J Perinatol. 2018;38(11):1496-1502. doi:10.1038/s41372-018-0218-4.
    • Contributed Indexing:
      Keywords: diazoxide; diazoxide adverse events; hyperinsulinism; hypoglycaemia treatment
    • Accession Number:
      O5CB12L4FN (Diazoxide)
    • Publication Date:
      Date Created: 20231207 Date Completed: 20240115 Latest Revision: 20240405
    • Publication Date:
      20240405
    • Accession Number:
      10.1111/cen.14987
    • Accession Number:
      38059644