ORIGINAL PAPER Fabian Yap Æ Wolfgang Ho¨gler Æ Amish Vora Robert Halliday Æ Geoffrey Ambler Severe transient hyperinsulinaemic hypoglycaemia: two neonates without predisposing factors and a review of the literature Received: 18 June 2003 / Accepted: 17 September 2003 / Published online: 29 October 2003 Ó Springer-Verlag 2003 Abstract We report on transient hyperinsulinism (HI), presenting as severe congenital HI, in two neonates born without intrauterine growth restriction, maternal diabetes, perinatal asphyxia or Rhesus/platelet isoim- munisation. The neonates developed early (<6 h of life), symptomatic, non-ketotic hypoglycaemia (0–0.66 mmol/l), associated with elevated insulin levels (40–200 mU/l), and required high glucose infusion rates (22–24 mg/kg per min) to maintain normoglycaemia. However, both babies were diazoxide-sensitive and did not require glucose infusions beyond 2 weeks of life. Neither neonate had elevated serum ammonia levels or evidence of a metabolic disorder. Conclusion: Tran- sient hyperinsulinism can occur in newborns delivered uneventfully without significant perinatal complica- tions. The unusual sensitivity to medical treatment in these cases of neonatal-onset hyperinsulinaemic hypoglycaemia underscores the importance of careful medical management of severe congenital hyperinsu- linism. Careful consideration of the indication and if necessary, timing and extent of pancreatectomy is re- quired, while maintaining euglycaemia to protect the developing brain. Keywords Congenital hyperinsulinism Æ Diazoxide Æ Hypoglycaemia Æ Neonates Æ Transient hyperinsulinism Abbreviations AGA appropriate for gestational age Æ BGL blood glucose level Æ BWS Beckwith-Wiedemann syndrome Æ HI hyperinsulinism Æ HI/HA hyperinsuli- nism/hyperammonaemia Æ IUGR intrauterine growth restriction Æ PHHI persistent hyperinsulinaemic hypo- glycaemia of infancy Æ SGA small for gestational age Æ SUR sulphonylurea receptor Æ TNHI transient neonatal hyperinsulinism Æ UVC umbilical venous catheter Introduction Neonatal-onset persistent hyperinsulinaemic hypo- glycaemia of infancy (PHHI) is a form of congenital hyperinsulinism (HI) which is usually severe, unlikely to be diazoxide sensitive [8, 20,24] and requires pancrea- tectomy in the majority of cases [12]. It is possible, however, that hyperinsulinaemic hypoglycaemia in neonates will resolve completely and spontaneously [8,25], a condition known as transient HI. Transient neonatal HI (TNHI) is well described in small for gestational age (SGA) and asphyxiated new- borns [5, 6, 7, 10, 11,19]. Additionally, HI occurs and resolves within 1 or 2 days in neonates born to mothers with poorly controlled diabetes [13,22]. Infants with Beckwith-Wiedemann syndrome (BWS) have b-cell hyperplasia and may experience either prolonged or transient HI [16]. Other very rare causes of TNHI are Rhesus or platelet isoimmunisation [1,4], sepsis, cerebral haemorrhage, severe stress and the hyperinsulinism-hy- perammonaemia (HI/HA) syndrome [23]. To our knowledge, TNHI has not been reported so far in neo- nates without perinatal complications and with normal birth size parameters. Eur J Pediatr (2004) 163: 38–41 DOI 10.1007/s00431-003-1328-2 F. Yap (&) Æ W. Ho¨gler Æ G. Ambler Institute of Endocrinology and Diabetes, The ChildrenÕs Hospital at Westmead, Corner Hawkesbury Road and Hainsworth Street, Locked Bag 4001, NSW 2145 Westmead, Sydney, Australia E-mail: fabiany@kkh.com.sg Tel.: +65-63941108 Fax: +65-63941114 A. Vora Æ R. Halliday Department of Neonatology, The ChildrenÕs Hospital at Westmead, Sydney, Australia Present address: F. Yap Department of Paediatrics, KK WomenÕs and ChildrenÕs Hospital, Singapore Present address: W. Ho¨gler Department of Paediatrics, University of Innsbruck, Innsbruck, Austria