11-Oxygenated Androgens are Biomarkers of Adrenal Volume and Testicular Adrenal Rest Tumors in 21-Hydroxylase Deficiency.

11-Oxygenated Androgens are Biomarkers of Adrenal Volume and Testicular Adrenal Rest Tumors in 21-Hydroxylase Deficiency.

J Clin Endocrinol Metab. 2017 May 01;:

Authors: Turcu AF, Mallappa A, Elman M, Avila NA, Marko J, Rao H, Tsodikov A, Auchus RJ, Merke DP

Abstract
Context: Patients with 21-hydroxylase deficiency (21OHD) suffer from long-term complications, which might result from poor disease control and/or glucocorticoid overtreatment. Lack of optimal biomarkers has made it challenging to tailor therapy and to predict long-term outcomes.
Objective: To identify biomarkers of disease control and long-term complications in 21OHD.
Setting and participants: Cross-sectional study of 114 patients (70 males), ages 2 to 67 (median, 15) years, seen in a tertiary referral center.
Methods: We correlated a mass-spectrometry panel of 23 steroids, obtained prior to first morning medication, with: bone age advancement (children), adrenal volume (adults), testicular adrenal rest tumors (TART), hirsutism, menstrual disorders, and pituitary hormones.
Results: Total adrenal volume correlated positively with 18/23 steroids, most prominently four 11-oxygenated-C19 (11oxC19) steroids: 11β-hydroxy- and 11-ketoandrostenedione (11OHA4, 11ketoA4), 11β-hydroxy- and 11-ketotestosterone (11OHT, 11ketoT) and 21-deoxycortisol (r≈0.7, p<0.0001). After age adjustment, 9/ 23 steroids were higher in males with compared to those without TART, including: 11OHA4 (6.8-fold, p=0.004), 11OHT (4.9-fold, p=0.002); 11ketoT (3.6-fold, p=0.004); 11ketoA4 (3.3-fold, p=0.01) and pregnenolone sulfate (PregS, 4.8-fold, p=0.007). PregS (28.5 fold) and 17OHPregS (19-fold) were higher (p<0.01) in postpubertal females with menstrual disorders. In males, testosterone (T) correlated positively with all 11oxC19 steroids in Tanner stages 1-2 (r=0.6-0.8, p<0.001), but negatively in Tanner stage 5 (r=-0.3, p<0.05 for 11ketoA4 and 11ketoT). In females, T correlated positively with all four 11oxC19 steroids across all Tanner stages (r=0.75-0.84, p< 0.0001).
Conclusion: 11oxC19 steroids and PregS might serve as clinically useful biomarkers of disease control and long-term complications in 21OHD.

PMID: 28472487 [PubMed - as supplied by publisher]

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