Endocrine Abstracts

Objective: This study was aimed to evaluate the prevalence of non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in hyperandrogenic women in the reproductive age attending our Endocrinology Unit and to identify specific phenotypic traits among clinical, biochemical and hormonal features.

Setting: Outpatient Unit of Endocrinology, S. Orsola-Malpighi University Hospital of Bologna, Italy.

Patients and methods: Among a population of 1079 women who attended our Unit from 2003 to 2017 for hyperandrogenic complaints, we selected 70 subjects having basal 17 hydroxyprogesterone (17OHP) levels in the follicular phase of the menstrual cycle ≥200 ng/dl measured by immunoassay. All these 70 patients performed CYP21A2 gene analysis by direct DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). They also performed an ovarian ultrasonography, a 1-24ACTH test, a complete basal steroid profiling measured both by immunoassay and by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), all 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 CYP21A2gene(C). As expected, these three groups resulted significantly different for basal 17OHP levels measured by immunoassay even though there was an overlap among them [21-NCAH:1971±2550 ng/dl (from 228 to 12,420); 21 HTZ: 287±85 ng/dl (from 196 to 452); C: 305±100 ng/dl (from 201 to 624)]. At variance, basal 17OHP measured by LC-MS/MS discriminated the 21-NCAH group from the others without any overlap [21-NCAH: 16.9±23.1 ng/ml (from 3.5 to 51.5); 21 HTZ: 1.7±0.9 ng/ml (from1.1 to 2.9); C: 1.4±0.3 ng/ml (from 1.1 to 1.8)]. Furthermore, in 21-NCAH patients 21-deoxycortisol levels were found significantly higher than in the other groups (0.58±0.32 ng/ml vs. 0.14±0.08 ng/ml in 21 HTZ and 0.11±0.06 ng/ml in C, P<0.05). In addition, cortisol and corticosterone measured by LC-MS/MS were significantly lower in 21-NCAH group (cortisol: 61.6±46.9 ng/ml; corticosterone 1.1±0.9 ng/ml) than in 21-HTZ (cortisol: 182±27 ng/ml; corticosterone: 12.1±9.7 ng/ml) and C (cortisol: 169±26 ng/ml; corticosterone 14.4±5.2 ng/ml) groups.

Conclusion: This study confirms that the prevalence of 21-NCAH of new diagnosis among hyperandrogenic women in the reproductive age is high accounting for 2.2%. In addition, it demonstrates that a basal blood steroid profiling measured by LC-MS/MS in the follicular phase of the menstrual cycle and composed by 17OHP, 21-deoxycortisol, cortisol and corticosterone is a valid diagnostic tool in 21-NCAH patients.