title: Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children.
abstract: OBJECTIVE
  Based on adult data, a peak cortisol response ≥500 nmol/l to insulin-induced hypoglycaemia constitutes a normal. Age-specific reference ranges for basal morning cortisol have been developed for clinical use in the paediatric population. Such reference ranges are not clearly established for peak cortisol responses to insulin-induced hypoglycaemia despite limited data suggesting an effect of age on peak cortisol. The aims of this study were to assess factors affecting the cortisol response to insulin-induced hypoglycaemia in children and to determine whether the peak cortisol response was related to age.
  
  
  METHODS
  The present study was a retrospective cohort study.
  
  
  METHODS
  Retrospective analysis of children and adolescents aged ≤18 years undergoing the insulin tolerance test with adequate hypoglycaemia was undertaken. Patients with hypopituitarism or severe hypothalamic-pituitary-adrenal axis impairment (peak cortisol value <400 nmol/l) or using systemic glucocorticoids were excluded.
  
  
  RESULTS
  Two hundred and twenty-three tests were analysed. Peak cortisol responses ≥500 nmol/l occurred in 183 (82%) tests. Age was negatively associated with peak cortisol responses (r=-0.15, P=0.03). A peak cortisol response <500 nmol/l was significantly less common in patients aged <12 years (9/97 (9%) vs 31/126 (25%); P=0.004). In children aged <12 years, the median (5th-95th centiles) peak cortisol values were 610 (480-806) nmol/l compared with 574 (442-789) nmol/l in children aged ≥12 years (P<0.004). Similarly, median cortisol increment was significantly higher in younger patients (301 nmol/l compared with 226 nmol/l (P=0.0004)).
  
  
  CONCLUSIONS
  Use of a single peak cortisol threshold in children of all ages is not appropriate and will result in overdiagnosis of adrenal insufficiency in adolescents.
authors.affiliation: Department of Paediatric Endocrinology and Diabetes, Our Lady's Children's Hospital, Dublin 12, Ireland. michaelogrady@physicians.ie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Grady
authors.forename: Conor
authors.initials: C
authors.lastname: Hensey
authors.forename: Miriam
authors.initials: M
authors.lastname: Fallon
authors.forename: Hilary
authors.initials: H
authors.lastname: Hoey
authors.forename: Nuala
authors.initials: N
authors.lastname: Murphy
authors.forename: Colm
authors.initials: C
authors.lastname: Costigan
authors.forename: Declan
authors.initials: D
authors.lastname: Cody
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007003:Hypoglycemia / Q000097:blood* / Q000139:chemically induced; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values; D012189:Retrospective Studies
chemical_list: D007328:Insulin; D006854:Hydrocortisone