title: Two-step biochemical differential diagnosis of classic 21-hydroxylase deficiency and cytochrome P450 oxidoreductase deficiency in Japanese infants by GC-MS measurement of urinary pregnanetriolone/ tetrahydroxycortisone ratio and 11β-hydroxyandrosterone.
abstract: BACKGROUND
  The clinical differential diagnosis of classic 21-hydroxylase deficiency (C21OHD) and cytochrome P450 oxidoreductase deficiency (PORD) is sometimes difficult, because both deficiencies can have similar phenotypes and high blood concentrations of 17α-hydroxyprogesterone (17OHP). The objective of this study was to identify biochemical markers for the differential diagnosis of C21OHD, PORD, and transient hyper 17α-hydroxyprogesteronemia (TH17OHP) in Japanese newborns. We established a 2-step biochemical differential diagnosis of C21OHD and PORD.
  
  
  METHODS
  We recruited 29 infants with C21OHD, 9 with PORD, and 67 with TH17OHP, and 1341 control infants. All were Japanese and between 0 and 180 days old; none received glucocorticoid treatment before urine sampling. We measured urinary pregnanetriolone (Ptl), the cortisol metabolites 5α- and 5β-tetrahydrocortisone (sum of these metabolites termed THEs), and metabolites of 3 steroids, namely dehydroepiandrosterone, androstenedione (AD4), and 11β-hydroxyandrostenedione (11OHAD4) by GC-MS.
  
  
  RESULTS
  At a cutoff of 0.020, the ratio of Ptl to THEs differentiated C21OHD and PORD from TH17OHP and controls with no overlap. Among metabolites of DHEA, AD4, and 11OHAD4, only 11β-hydroxyandrosterone (11HA), a metabolite of 11OHAD4, showed no overlap between C21OHD and PORD at a cutoff of 0.35 mg/g creatinine.
  
  
  CONCLUSIONS
  A specific cutoff for the ratio of Ptl to THEs can differentiate C21OHD and PORD from TH17OHP and controls. Additionally, the use of a specific cutoff of 11HA can distinguish between C21OHD and PORD.
authors.affiliation: Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Koyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Homma
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miwa
authors.forename: Kazushige
authors.initials: K
authors.lastname: Ikeda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis*; D000738:Androsterone / Q000031:analogs & derivatives* / Q000652:urine; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009251:NADPH-Ferrihemoprotein Reductase / Q000172:deficiency* / Q000235:genetics; D011279:Pregnanetriol / Q000031:analogs & derivatives* / Q000652:urine; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D013761:Tetrahydrocortisone / Q000652:urine*
chemical_list: D015415:Biomarkers; D011279:Pregnanetriol; C002528:11 beta-hydroxyandrosterone; D013761:Tetrahydrocortisone; C009030:pregnanetriolone; D019326:17-alpha-Hydroxyprogesterone; D000738:Androsterone; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D009251:NADPH-Ferrihemoprotein Reductase