title: Recurrent spontaneous hypoglycaemia causes loss of neurogenic and neuroglycopaenic signs in infants with congenital hyperinsulinism.
abstract: OBJECTIVE
  Hypoglycaemia-associated autonomic failure (HAAF) with impaired neurogenic and neuroglycopaenic responses occurs in adults following recent, repeated hypoglycaemia. We aimed to evaluate whether HAAF also occurs in patients with infant-onset congenital hyperinsulinism (CHI).
  
  
  METHODS
  A controlled fast was performed in (i) seven CHI infants with initial symptomatic hypoglycaemia and three recent episodes of spontaneous recurrent hypoglycaemia each lasting <5 min and in (ii) seven infants with idiopathic ketotic hypoglycaemia for control.
  
  
  METHODS
  At the time of hypoglycaemia (blood glucose <3 mmol/l or clinical signs), blood was drawn for serum insulin, cortisol, glucagon, adrenalin and nor-adrenalin. Signs of hypoglycaemia were documented. In CHI patients, the ABCC8 and KCNJ11 genes were analysed by denaturing high performance liquid chromatography (DHPLC) and/or direct bidirectional sequencing.
  
  
  RESULTS
  Two CHI patients had a paternal ABCC8 mutation, five had no mutations. When repeated hypoglycaemia was provoked, all CHI patients exhibited a complete loss of clinical signs of hypoglycaemia, along with a global blunting of the counter-regulatory hormones cortisol, glucagon, growth hormone, adrenalin and nor-adrenalin responses (median values 256 nmol/l, 23 pmol/l, 5·6 mU/l, 390 pmol/l and 2·9 nmol/l, respectively), irrespective of mutational status. In the controls, hypoglycaemia was always clinically overt with normal counter-regulatory cortisol, glucagon, adrenalin and nor-adrenalin responses (530 nmol/l, 60, 920 pmol/l and 4·0 nmol/l, respectively).
  
  
  CONCLUSIONS
  Recurrent hyperinsulinaemic hypoglycaemia even of short duration blunts the autonomic, neuroglycopaenic and glucose counter-regulatory hormonal responses in patients with infant-onset CHI resulting in clinically silent hypoglycaemia. Tight, or continuous, glucose monitoring is therefore recommended, especially in conservatively treated patients.
authors: HC Andersen Children's Hospital, Odense, Denmark.
authors: Henrik T
authors: HT
authors: Christesen
authors: Klaus
authors: K
authors: Brusgaard
authors: Khalid
authors: K
authors: Hussain
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D044903:Congenital Hyperinsulinism / Q000097:blood* / Q000503:physiopathology; D004837:Epinephrine / Q000097:blood; D005215:Fasting / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000503:physiopathology; D007223:Infant; D007328:Insulin / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D009638:Norepinephrine; D004837:Epinephrine