Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of P
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ORIGINAL ARTICLE
Steroid biomarkers for identifying non‑classic adrenal hyperplasia due to 21‑hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH‑progesterone C. Oriolo1 · F. Fanelli1 · S. Castelli1 · M. Mezzullo1 · P. Altieri1 · F. Corzani1 · C. Pelusi1 · A. Repaci1 · G. Di Dalmazi1 · V. Vicennati1 · L. Baldazzi3 · S. Menabò3 · A. Dormi2 · E. Nardi2 · G. Brillanti2 · R. Pasquali1 · U. Pagotto1 · A. Gambineri1 Received: 20 November 2019 / Accepted: 20 March 2020 © Italian Society of Endocrinology (SIE) 2020
Abstract Objective We aimed at defining the most effective routine immunoassay- or liquid chromatography-tandem mass spectrometry (LC–MS/MS)-determined steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in a PCOS-like population before genotyping. Methods Seventy PCOS-like patients in reproductive age with immunoassay-determined follicular 17OH-progesterone (17OHP) ≥ 2.00 ng/mL underwent CYP21A2 gene analysis and 1–24ACTH test. Serum steroids were measured by immunoassays at baseline and 60 min after ACTH stimulation; basal steroid profile was measured by LC–MS/MS. Results Genotyping revealed 23 21-NCAH, 15 single allele heterozygous CYP21A2 mutations (21-HTZ) and 32 PCOS patients displaying similar clinical and metabolic features. Immunoassays revealed higher baseline 17OHP and testosterone, and after ACTH stimulation, higher 17OHP (17OHP60) and lower cortisol, whereas LC–MS/MS revealed higher 17OHP (17OHPLC-MS/MS), progesterone and 21-deoxycortisol and lower corticosterone in 21-NCAH compared with both 21-HTZ and PCOS patients. Steroid thresholds best discriminating 21-NCAH from 21-HTZ and PCOS were estimated, and their diagnostic accuracy in identifying 21-NCAH from PCOS was established by ROC analysis. The highest accuracy was observed for 21-deoxycortisol ≥ 0.087 ng/mL, showing 100% sensitivity, while the combination of 17OHPLC-MS/MS ≥ 1.79 ng/mL and corticosterone ≤ 8.76 ng/mL, as well as the combination of ACTH-stimulated 17OHP ≥ 6.77 ng/mL and cortisol ≤ 240 ng/ mL by immunoassay, showed 100% specificity. Conclusions LC–MS/MS measurement of basal follicular 21-deoxycortisol, 17OHP and corticosterone seems the most convenient method for diagnosing 21-NCAH in a population of PCOS with a positive first level screening, providing high accuracy and reducing the need for ACTH stimulation test. Keywords Polycystic ovary syndrome · Non-classic adrenal hyperplasia due to 21-hydroxylase deficiency · CYP21A2 genotyping · 1–24ACTH test · Steroid profiling
Introduction C. Oriolo and F. Fanelli shared first authorship. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40618-020-01235-3) contains supplementary material, which is available to authorized users. * A. Gambineri [email protected] 1
Endocrinology Unit and Centre for Applied Biomedical Research (CRBA), Department of Medical and Surgical Sciences, St. Orsola Hospital, University of Bologna, Via Massare
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