Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency.

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TitleProfiles of 21-Carbon Steroids in 21-hydroxylase Deficiency.
Publication TypeJournal Article
Year of Publication2015
AuthorsTurcu AF, Rege J, Chomic R, Liu J, Nishimoto HK, Else T, Moraitis AG, Palapattu GS, Rainey WE, Auchus RJ
JournalJ Clin Endocrinol Metab
Volume100
Issue6
Pagination2283-90
Date Published2015 Jun
ISSN1945-7197
Keywords17-alpha-Hydroxyprogesterone, Adrenal Hyperplasia, Congenital, Adrenal Rest Tumor, Adult, Case-Control Studies, Cells, Cultured, Cortodoxone, Female, Humans, Hydroxyprogesterones, Male, Metabolome, Middle Aged, Progesterone, Testicular Neoplasms, Young Adult
Abstract

CONTEXT: Marked elevations of 17-hydroxyprogesterone (17OHP) are characteristic of classic 21-hydroxylase deficiency (21OHD). Testing of 17OHP provides the basis for 21OHD diagnosis, although it suffers from several pitfalls. False-positive or false-negative results and poor discrimination of nonclassic 21OHD from carriers limit the utility of serum 17OHP and necessitate dynamic testing after cosyntropin stimulation when values are indeterminate.OBJECTIVE: The objective was to provide a detailed characterization of 21-carbon (C21) steroids in classic 21OHD, which might identify other candidate steroids that could be employed for the diagnosis of 21OHD.SETTING AND PARTICIPANTS: Patients (11 women, 10 men) with classic 21OHD and 21 sex- and age-matched controls seen in a tertiary referral center were studied.METHODS: C21 steroids in the peripheral sera from all subjects, as well as in media from cultured testicular adrenal rest tumor (TART) cells and normal adrenal (NA) cells, were analyzed using liquid chromatography/tandem mass spectrometry (10 steroids). Additionally, the dynamics of C21 steroid metabolism in TART and NA cells were assessed with radiotracer studies.RESULTS: Five C21 steroids were significantly higher in 21OHD patients: 17OHP (67-fold; P < .01), 21-deoxycortisol (21dF; 35-fold; P < .01), 16α-hydroxyprogesterone (16OHP; 28-fold; P < .01), progesterone (2-fold; P < .01), and 11β-hydroxyprogesterone (11OHP; not detected in controls; P < .01). The same steroids were the highest in media from TART cells relative to the NA cells: 11OHP, 58- to 65-fold; 21dF, 30- to 41-fold; 17OHP, 9-fold; progesterone, 9- to 12-fold; and 16OHP, 7-fold.CONCLUSION: Measurement of 16OHP and 11OHP along with 17OHP and 21dF by liquid chromatography/tandem mass spectrometry might comprise a biomarker panel to accurately diagnose all forms of 21OHD.

DOI10.1210/jc.2015-1023
Alternate JournalJ. Clin. Endocrinol. Metab.
PubMed ID25850025
PubMed Central IDPMC4454804
Grant ListDK089503 / DK / NIDDK NIH HHS / United States
F32 DK103461 / DK / NIDDK NIH HHS / United States
F32DK103461 / DK / NIDDK NIH HHS / United States
R01 DK069950 / DK / NIDDK NIH HHS / United States
R01DK069950 / DK / NIDDK NIH HHS / United States
R01GM086596 / GM / NIGMS NIH HHS / United States
U24 DK097153 / DK / NIDDK NIH HHS / United States