title: Distinctive profile of the 17-hydroxylase and 17,20-lyase activities revealed by urinary steroid metabolomes of patients with CYP17 deficiency.
abstract: OBJECTIVE
  (1) Characterize serum (S) and urinary (U) steroid metabolites in complete CYP17 deficiency (cCYP17D); (2) analyze the relative 17α-hydroxylase (17OH) and 17,20-lyase (17,20L) activities in vivo; and (3) comparedata from the two most prevalent mutations in Brazil.
  
  
  METHODS
  20 genotyped cCYP17D patients from a previously reported cohort were homozygous for W406R or R362C; 11 controls were CYP17 wild types (WT). WT and cCYP17D patients had S and U samples drawn to measure: cortisol (F), corticosterone (B), deoxycorticosterone (DOC), 18OH-B, 18OH-DOC, and 17OHP; and tetrahydro (TH)-B, THA, THDOC, THF+5α-THF, TH-cortisone, androsterone, etiocholanolone, 5-pregnenediol, 17OH-pregnenolone and pregnanetriol.
  
  
  RESULTS
  Compared to WT, cCYP17D patients had marked elevations of B, DOC, 18OH-B and 18OH-DOC, whereas 17OHP, F and adrenal androgens (AA) were reduced; U steroids parallel S findings. Metabolite ratios revealed that both 17OH and 17,20L activities were impaired in cCYP17D. There were nodifferences between W406R andR362C mutations.
  
  
  CONCLUSIONS
  cCYP17D patients show parallel overproduction/overexcretion of 17-deoxysteroids, and marked reduction of F and AA. In addition to 17OH, 17,20-L activity was also impaired in cCYP17D. W406 and R362C mutations disclose similar Sand U patterns.
authors.affiliation: Adrenal and Hypertension Unit, Division of Endocrinology and Metabolism, Department of Medicine, Universidade Federal de São Paulo, SP, Brazil.
authors.forename: Marcos S
authors.initials: MS
authors.lastname: Neres
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Auchus
authors.forename: Cedric H L
authors.initials: CH
authors.lastname: Shackleton
authors.forename: Claudio E
authors.initials: CE
authors.lastname: Kater
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics / Q000652:urine*; D000328:Adult; D000728:Androgens / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000652:urine*; D055815:Young Adult
chemical_list: D000728:Androgens; D013254:Steroid 17-alpha-Hydroxylase; D006854:Hydrocortisone