title: Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency.
abstract: OBJECTIVE
  To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation.
  
  
  METHODS
  Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies.
  
  
  METHODS
  We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals.
  
  
  RESULTS
  Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals.
  
  
  CONCLUSIONS
  All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess.
authors: Division of MetabolismEndocrinology and Diabetes, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA.
authors: Adina F
authors: AF
authors: Turcu
authors: Division of MetabolismEndocrinology and Diabetes, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA.
authors: Aya T
authors: AT
authors: Nanba
authors: Michigan Metabolomics and Obesity CenterUniversity of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA.
authors: Robert
authors: R
authors: Chomic
authors: Division of MetabolismEndocrinology and Diabetes, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA.
authors: Sunil K
authors: SK
authors: Upadhyay
authors: Department of PathologyUniversity of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA.
authors: Thomas J
authors: TJ
authors: Giordano
authors: Department of RadiologyUniversity of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA.
authors: James J
authors: JJ
authors: Shields
authors: Pediatric ServicesNational Institutes of Health Clinical Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, 10 Center Drive, Bethesda, MD, 20892, USA.
authors: Deborah P
authors: DP
authors: Merke
authors: Division of MetabolismEndocrinology and Diabetes, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA Department of Molecular and Integrative Physiology and MedicineUniversity of Michigan, Ann Arbor, Michigan, USA.
authors: William E
authors: WE
authors: Rainey
authors: Division of MetabolismEndocrinology and Diabetes, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan, 48109, USA Department of PharmacologyUniversity of Michigan, Ann Arbor, Michigan, USA rauchus@med.umich.edu.
authors: Richard J
authors: RJ
authors: Auchus
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007664:Ketosteroids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007664:Ketosteroids; D013739:Testosterone