Objective: The aim of this study was to define which hormonal cut-off values can discriminate polycystic ovary syndrome (PCOS) from non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH).
Patients and methods: We included 70 women in reproductive age who attended our Unit from 2003 to 2018 for a diagnosis of PCOS with a basal 17hydroxyprogesterone (17OHP) level in the follicular phase of the menstrual cycle ≥200 ng/dl measured by 17OHP Bridge RIA immunoassay (Adaltis, Guidonia, Italy). All patients performed CYP21A2 gene analysis by direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA), that we used to discriminate PCOS from 21-NCAH. They also performed a 1-24ACTH test in the follicular phase of the menstrual cycle.
Results: Twenty-three patients resulted affected by 21-NCAH, 15 were found to be heterozygotes for the 21-hydroxylase deficiency (21-HTZ) and 32 had no mutations for CYP21A2 gene (21-NM). As expected, the three groups significantly differed for basal 17OHP levels (21-NCAH: 2072±2671 ng/dl; 21-HTZ: 298±88 ng/dl; 21-NM: 322±110 ng/dl; P value <0.001). Accordingly, 17OHP levels at 60 minutes of the 1-24ACTH test (17OHP60) resulted significantly higher in affected than in unaffected patients; (21-NCAH: 5022±5203 ng/dl; 21-HTZ: 638±393 ng/dl; 21-NM: 515±290 ng/dl; P value <0.001). Cut-offs were generated for basal 17OHP and 17OHP60 by linear interpolation methods of determining quartiles. The cut-off values yielding the best sensitivity were ≥350 ng/dl for basal 17OHP and ≥677 ng/dl for 17OHP60. Using these cut-off values 1/23 patient with 21-NCAH (4%) could be diagnosed as PCOS, whereas 4/47 PCOS (8%), 3 of 21-NM group and 1 of 21-HTZ group, could be diagnosed as 21-NCAH.
Conclusion: We found that the contemporary use of basal and stimulated 17OHP is a valid diagnostic method to distinguish 21-NCAH from PCOS. The best thresholds seem to be 350 ng/dl for basal 17OHP and 677 ng/dl for 17OHP60, as measured by RIA immunoassay, still being nowadays the most used way to measure 17OHP in italian labs.
18 - 21 May 2019
European Society of Endocrinology