Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency - PubMed (original) (raw)

Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency

Adina F Turcu et al. J Clin Endocrinol Metab. 2015 Jun.

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.

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Figures

Figure 1.

Figure 1.

Steroid metabolism in TART cells and normal adrenal (NA) cells. Cells were first treated with ACTH (10 nmol/L) or experimental medium for 48 hours. Immediately after media collection, cells were incubated with medium containing pregnenolone (P5), progesterone (P4), or 17OHP (1 μmol/L) and the corresponding [3H]labeled steroid (106 cpm/mL). Aliquots of medium were collected at 2, 4, and 8 hours. Samples were extracted, and radioactivity was quantified using HPLC. Data shown represent the percentage of total detected radiolabeled steroids (% steroid). 17OHP5, 17α-hydroxypregnenolone; 11DOC, 11-deoxycorticosterone.

Figure 2.

Figure 2.

Pathways of C21 steroids synthesis in 21OHD. HSD3B2, 3β-hydroxysteroid dehydrogenase type 2; CYP17A1, 17α-hydroxylase/17,20-lyase; CYB5A, cytochrome _b_5 type A; CYP11B1, 11β-hydroxylase; CYP11B2, aldosterone synthase; HSD17B5, 17β-hydroxysteroid dehydrogenase type 5.

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