OBJECTIVES: (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. SUBJECTS AND 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.
OBJECTIVES: (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. SUBJECTS AND 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: Nils Krone; Nicole Reisch; Jan Idkowiak; Vivek Dhir; Hannah E Ivison; Beverly A Hughes; Ian T Rose; Donna M O'Neil; Raymon Vijzelaar; Matthew J Smith; Fiona MacDonald; Trevor R Cole; Nicolai Adolphs; John S Barton; Edward M Blair; Stephen R Braddock; Felicity Collins; Deborah L Cragun; Mehul T Dattani; Ruth Day; Shelley Dougan; Miriam Feist; Michael E Gottschalk; John W Gregory; Michaela Haim; Rachel Harrison; Ann Haskins Olney; Berthold P Hauffa; Peter C Hindmarsh; Robert J Hopkin; Petr E Jira; Marlies Kempers; Michiel N Kerstens; Mohamed M Khalifa; Birgit Köhler; Dominique Maiter; Shelly Nielsen; Stephen M O'Riordan; Christian L Roth; Kate P Shane; Martin Silink; Nike M M L Stikkelbroeck; Elizabeth Sweeney; Maria Szarras-Czapnik; John R Waterson; Lori Williamson; Michaela F Hartmann; Norman F Taylor; Stefan A Wudy; Ewa M Malunowicz; Cedric H L Shackleton; Wiebke Arlt Journal: J Clin Endocrinol Metab Date: 2011-12-07 Impact factor: 5.958
Authors: Jan Idkowiak; Tabitha Randell; Vivek Dhir; Pushpa Patel; Cedric H L Shackleton; Norman F Taylor; Nils Krone; Wiebke Arlt Journal: J Clin Endocrinol Metab Date: 2011-12-14 Impact factor: 5.958
Authors: Karl-Heinz Storbeck; Lina Schiffer; Elizabeth S Baranowski; Vasileios Chortis; Alessandro Prete; Lise Barnard; Lorna C Gilligan; Angela E Taylor; Jan Idkowiak; Wiebke Arlt; Cedric H L Shackleton Journal: Endocr Rev Date: 2019-12-01 Impact factor: 19.871
Authors: Min Sun; Jonathan W Mueller; Lorna C Gilligan; Angela E Taylor; Fozia Shaheen; Anna Noczyńska; Guy T'Sjoen; Louise Denvir; Savitha Shenoy; Piers Fulton; Timothy D Cheetham; Helena Gleeson; Mushtaqur Rahman; Nils P Krone; Norman F Taylor; Cedric H L Shackleton; Wiebke Arlt; Jan Idkowiak Journal: Eur J Endocrinol Date: 2021-10-11 Impact factor: 6.664