Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency

Author:

Turcu Adina F,Nanba Aya T,Chomic Robert,Upadhyay Sunil K,Giordano Thomas J,Shields James J,Merke Deborah P,Rainey William E,Auchus Richard J

Abstract

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. Design 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.

Publisher

Bioscientifica

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

Reference34 articles.

1. Congenital Adrenal Hyperplasia

2. Clinical review 56: Nonclassic adrenal hyperplasia: current concepts

3. Fertility in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency;Stikkelbroeck;Obstetrical & Gynecological Survey,2003

4. Cabrera MS Vogiatzi MG New MI. Long term outcome in adult males with classic congenital adrenal hyperplasia. Journal of Clinical Endocrinology & Metabolism 2001 86 3070–3078. (doi:10.1210/jcem.86.7.7668)

5. Reisch N Flade L Scherr M Rottenkolber M Pedrosa Gil F Bidlingmaier M Wolff H Schwarz HP Quinkler M Beuschlein F et al. High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. Journal of Clinical Endocrinology & Metabolism 2009 94 1665–1670. (doi:10.1210/jc.2008-1414)

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