Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone

Autor: S Castelli, Flaminia Fanelli, G. Di Dalmazi, Alessandra Gambineri, Valentina Vicennati, Lilia Baldazzi, G Brillanti, Uberto Pagotto, Andrea Repaci, Paola Altieri, Soara Menabo, C. Pelusi, Renato Pasquali, Marco Mezzullo, Elena Nardi, A Dormi, Francesca Corzani, Claudia Oriolo
Přispěvatelé: Oriolo C., Fanelli F., Castelli S., Mezzullo M., Altieri P., Corzani F., Pelusi C., Repaci A., Di Dalmazi G., Vicennati V., Baldazzi L., Menabo S., Dormi A., Nardi E., Brillanti G., Pasquali R., Pagotto U., Gambineri A.
Rok vydání: 2019
Předmět:
Adult
medicine.medical_specialty
Adolescent
Genotyping Techniques
Endocrinology
Diabetes and Metabolism
Population
DNA Mutational Analysis
Steroid profiling
CYP21A2 genotyping
ACTH test
Cohort Studies
Diagnostic Techniques
Endocrine
Basal (phylogenetics)
chemistry.chemical_compound
Young Adult
Endocrinology
Corticosterone
Tandem Mass Spectrometry
Internal medicine
Follicular phase
Medicine
Humans
Testosterone
education
education.field_of_study
medicine.diagnostic_test
biology
Adrenal Hyperplasia
Congenital
business.industry
17-alpha-Hydroxyprogesterone
ACTH stimulation test
21-Hydroxylase
Reproducibility of Results
Hyperplasia
Non-classic adrenal hyperplasia due to 21-hydroxylase deficiency
medicine.disease
1–24
chemistry
biology.protein
Female
Steroids
Steroid 21-Hydroxylase
business
Biomarkers
Blood Chemical Analysis
Chromatography
Liquid
Polycystic Ovary Syndrome
Zdroj: Journal of endocrinological investigation. 43(10)
ISSN: 1720-8386
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: