title: The balance of cortisol-cortisone interconversion is shifted towards cortisol in neonates with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
abstract: BACKGROUND
  Patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) have an impaired cortisol synthesis, but it is unknown whether the metabolism of glucocorticoids differs between neonates and infants with and without 21OHD.
  
  
  OBJECTIVE
  The objective of this study was to compare the glucocorticoid metabolism between neonates and infants with and without 21OHD.
  
  
  METHODS
  We analyzed 14 urinary glucocorticoid metabolites, 7 metabolites each of cortisol and cortisone, by gas chromatography-mass spectrometry of 89 untreated 21OHD neonates and infants and 161 neonates and infants without 21OHD.
  
  
  RESULTS
  Neonates with 21OHD exhibit elevated relative amounts of cortisol metabolites in total glucocorticoid metabolism and an increased ratio of cortisol to cortisone metabolites (p<0.0001). This reflects a shift toward cortisol in the relative balance of the interconversion between cortisol and cortisone. The ratio of cortisol to cortisone metabolites correlated significantly with low urinary glucocorticoid concentrations (p<0.03), with low 21-hydroxylase activity (p<0.001) and high urinary sodium and chloride concentrations (p<0.05) in neonates with 21OHD.
  
  
  CONCLUSIONS
  Our results demonstrate substantial changes in the relative cortisone to cortisol interconversion in neonates with 21OHD. The shift of glucocorticoid metabolism toward active cortisol in neonates with 21OHD seems to be related to the severity of 21OHD and adrenal dysfunction. Our data provide new insights into the regulation of glucocorticoid homeostasis in 21OHD.
authors.affiliation: Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany; Steroid Research and Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany. Electronic address: Clemens.kamrath@paediat.med.uni-giessen.de.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kamrath
authors.affiliation: Steroid Research and Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Michaela F
authors.initials: MF
authors.lastname: Hartmann
authors.affiliation: Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany; Steroid Research and Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Wudy
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000473:pathology / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D003348:Cortisone / Q000652:urine*; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D007223:Infant; D007231:Infant, Newborn; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D003348:Cortisone; D006854:Hydrocortisone
keywords: 11β-Hydroxysteroid dehydrogenase; 21-Hydroxylase deficiency; Congenital adrenal hyperplasia; Cortisol metabolism