PMID- 38130465
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
IS  - 2472-1972 (Electronic)
IS  - 2472-1972 (Linking)
VI  - 8
IP  - 1
DP  - 2023 Dec 1
TI  - Multiplexed Serum Steroid Profiling Reveals Metabolic Signatures of Subtypes in 
      Congenital Adrenal Hyperplasia.
PG  - bvad155
LID - 10.1210/jendso/bvad155 [doi]
LID - bvad155
AB  - CONTEXT: Altered metabolic signatures on steroidogenesis may characterize 
      individual subtypes of congenital adrenal hyperplasia (CAH), but conventional 
      diagnostic approaches are limited to differentiate subtypes. OBJECTIVE: We 
      explored metabolic characterizations and identified multiple diagnostic 
      biomarkers specific to individual subtypes of CAH. METHODS: Liquid 
      chromatography-mass spectrometry-based profiling of 33 adrenal steroids was 
      developed and applied to serum samples obtained from 67 CAH patients and 38 
      healthy volunteers. RESULTS: Within- and between-run precisions were 95.4% to 
      108.3% and 94.1% to 110.0%, respectively, while all accuracies were <12% and the 
      correlation coefficients (r(2)) were > 0.910. Metabolic ratios corresponding to 
      21-hydroxylase characterized 21-hydroxylase deficiency (21-OHD; n = 63) from 
      healthy controls (area under the curve = 1.0, P < 1 x 10(-18) for all) and other 
      patients with CAH in addition to significantly increased serum 
      17alpha-hydroxyprogesterone (P < 1 x 10(-16)) and 21-deoxycortisol (P < 1 x 10(-15)) 
      levels. Higher levels of mineralocorticoids, such as corticosterone (B) and 
      18-hydroxyB, were observed in 17alpha-hydroxylase deficiency (17alpha-OHD; N = 3), while 
      metabolic ratio of dehydroepiandrosterone sulfate to pregnenolone sulfate was 
      remarkably decreased against all subjects. A patient with 11beta-hydroxylase 
      deficiency (11beta-OHD) demonstrated significantly elevated 11-deoxycortisol and its 
      metabolite tetrahydroxy-11-deoxyF, with reduced metabolic ratios of 
      11beta-hydroxytestosterone/testosterone and 
      11beta-hydroxyandrostenedione/androstenedione. The steroid profiles resulted in 
      significantly decreased cortisol metabolism in both 21-OHD and 17alpha-OHD but not in 
      11beta-OHD. CONCLUSION: The metabolic signatures with specific steroids and their 
      corresponding metabolic ratios may reveal individual CAH subtypes. Further 
      investigations with more substantial sample sizes should be explored to enhance 
      the clinical validity.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Shim, Jaeyoon
AU  - Shim J
AD  - Center for Advanced Biomolecular Recognition, Korea Institute of Science and 
      Technology, Seoul 02792, Korea.
AD  - Department of Chemistry, Korea University, Seoul 02841, Korea.
FAU - Ahn, Chang Ho
AU  - Ahn CH
AD  - Department of Internal Medicine, Seoul National University Bundang Hospital, 
      Gyeonggi-do 13620, Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul 03080, Korea.
FAU - Park, Seung Shin
AU  - Park SS
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul 03080, Korea.
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, 
      Korea.
FAU - Noh, Jongsung
AU  - Noh J
AD  - Center for Advanced Biomolecular Recognition, Korea Institute of Science and 
      Technology, Seoul 02792, Korea.
FAU - Lee, Chaelin
AU  - Lee C
AD  - Center for Advanced Biomolecular Recognition, Korea Institute of Science and 
      Technology, Seoul 02792, Korea.
FAU - Lee, Sang Won
AU  - Lee SW
AD  - Department of Chemistry, Korea University, Seoul 02841, Korea.
FAU - Kim, Jung Hee
AU  - Kim JH
AUID- ORCID: 0000-0003-1932-0234
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul 03080, Korea.
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, 
      Korea.
FAU - Choi, Man Ho
AU  - Choi MH
AUID- ORCID: 0000-0003-1017-1156
AD  - Center for Advanced Biomolecular Recognition, Korea Institute of Science and 
      Technology, Seoul 02792, Korea.
LA  - eng
GR  - 27300C0032/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20231221
PL  - United States
TA  - J Endocr Soc
JT  - Journal of the Endocrine Society
JID - 101697997
PMC - PMC10735290
OTO - NOTNLM
OT  - adrenal steroids
OT  - congenital adrenal hyperplasia
OT  - cortisol
OT  - hydroxylase deficiency
OT  - metabolic signatures
EDAT- 2023/12/22 06:42
MHDA- 2023/12/22 06:43
PMCR- 2023/12/21
CRDT- 2023/12/22 03:50
PHST- 2023/08/11 00:00 [received]
PHST- 2023/12/22 06:43 [medline]
PHST- 2023/12/22 06:42 [pubmed]
PHST- 2023/12/22 03:50 [entrez]
PHST- 2023/12/21 00:00 [pmc-release]
AID - bvad155 [pii]
AID - 10.1210/jendso/bvad155 [doi]
PST - epublish
SO  - J Endocr Soc. 2023 Dec 21;8(1):bvad155. doi: 10.1210/jendso/bvad155. eCollection 
      2023 Dec 1.