1.
24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency.
Turcu, AF, Mallappa, A, Nella, AA, Chen, X, Zhao, L, Nanba, AT, Byrd, JB, Auchus, RJ, Merke, DP
Frontiers in endocrinology. 2021;:751191
Abstract
BACKGROUND Optimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking. OBJECTIVE To compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling. PARTICIPANTS AND METHODS We studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I-II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI. RESULTS In response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men. CONCLUSION 11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.
2.
Management of Diabetic Macular Edema: Is It Time to Say Goodbye to Macular Laser?
Chen, X, Modjtahedi, BS, Young, LH
International ophthalmology clinics. 2015;(4):113-22