Adrenal steroid profiling as a diagnostic tool to differentiate polycystic ovary syndrome from nonclassic congenital adrenal hyperplasia: pinpointing easy screening possibilities and normal cutoff levels using liquid chromatography tandem mass spectrometry
Grethe Å Ueland, Sandra R Dahl, Paal Methlie, Saleh Hessen, Eystein S Husebye, Per M Thorsby, Grethe Å Ueland, Sandra R Dahl, Paal Methlie, Saleh Hessen, Eystein S Husebye, Per M Thorsby
Abstract
Objective: To define liquid chromatography tandem mass spectrometry (LC-MS/MS)-based cutoff levels and panels of steroid hormones, to improve diagnosis of nonclassic congenital adrenal hyperplasia (NCCAH) and other partial enzyme defects in the adrenals.
Design: Prospective cohort analysis.
Setting: University hospital-based tertiary endocrine center.
Patients: One hundred and twenty-one healthy adults and 65 patients evaluated for possible NCCAH (validation cohort).
Interventions: The LC-MS/MS-determined cutoffs for 11 steroids (basal and cosyntropin-stimulated) were defined by 2.5% and 97.5% percentile in healthy subjects. Validation cohort was used for comparison.
Main outcome measures: Percentage of patients diagnosed with NCCAH among patients with polycystic ovary syndrome (PCOS)-like symptomatology. Evaluation of the defined LC-MS/MS-based cutoff levels for steroid hormones among this patient group.
Results: Of the 65 PCOS-like patients evaluated for possible NCCAH, 8 (12.5%) were discovered and genetically verified, and 2 had classic congenital adrenal hyperplasia. Cosyntropin-stimulated 17-hydroxyprogesterone (17OHP) showed the best diagnostic accuracy for NCCAH with an area under the curve of 0.95 (0.89-1.0 with a sensitivity of 86% and a specificity of 88%. In homozygote patients, 21-deoxycortisol and 17OHP levels were elevated, in heterozygote patients only 17OHP (basal or stimulated) was raised. Four healthy patients in the validation cohort had 17OHP above the basal cutoff.
Conclusions: The NCCAH syndrome is frequent in patients with suspected PCOS, and should be considered as a routine screening when assessing infertility. We suggest the use of serum steroid profiling, including 21-deoxycortisol, together with the cosyntropin stimulation test with 17OHP. Our data support a 17OHP cutoff of 8.5 nmol/L (2.8 ng/mL) 60 minutes after cosyntropin stimulation, when measured with LC-MS/MS, significantly lower than current European guidelines.
Clinical trials number: NCT0218660.
Trial registration: ClinicalTrials.gov NCT00218660.
Keywords: NCCAH; Nonclassic congenital adrenal hyperplasia; PCOS; infertility; serum steroid profiling.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed