Background: To diagnose non classical congenital adrenal hyperplasia (NCCAH) and adrenal insufficiency (AI), current guidelines recommend ACTH test. Cutoffs for 17 hydroxyprogesterone (17OHP) and cortisol are derived from immunoassays values. Thanks to a recently developed and validated mass spectrometry approach (LC-MS/MS) we routinely quantify simultaneously 16 circulating steroids and we are able to speculate on new cut off values and uses.
Objective and hypotheses: We prospectively analyzed in children addressed to our endocrine unit for premature pubic hair, all steroids assayed by LC-MS/MS, basal and stimulated by ACTH tests. We searched for additional basal variables discriminant enough to the make the diagnosis.
Patients and Methods: Eighty-three patients were referred in our unit in 2017, because of premature pubic hair. Mean age was 7.3±2.3 yrs, sex ratio was 19 males and 64 females. Patients with stimulated 17 OHP values above 9 ng/ml and their parents gave their consent for molecular testing of CYP21A2 according to our local ethics committee. Hence 69 had a premature pubarche (PP), 9 a NCCAH and 5 male patients were excluded because of central puberty. Bone age was more advanced in the NCCAH group compared to the PP group 2.9 yrs versus 1.3 yrs.
Results: Mean basal 17 OHP ranged from 0.053 to 1.1 ng/ml in PP patients and from 3.62 to 87.94 ng/ml in NCCAH patients (P<0.0001). Mean basal 21-Deoxycortisol (21DF) was 0.03 ng/ml in PP patients and 3.42 ng/ml in NCCAH patients (P<0.0001). Basal Testosterone was 0.08 ng/ml in PP patients versus 0.2 ng/ml in NCCAH (P<0.0001). Basal Androstenedione was 0.28 ng/ml in PP patients and 0.94 ng/ml in NCCAH patients (P<0.0001) and 11 Beta-OH-Androstenedione was 0.57 ng/ml in PP patients versus 2.17 ng/ml in NCCAH patients (P <0.0001). ACTH tests revealed 6 AI among the 9 NCCAH patients. Stimulated 17 OHP was 0.279.06 ng/ml in the PP group versus 22.7392.57 ng/ml in NCCAH patients. Using multivariate data analysis (Partial Least Squares regression (PLS/PLS-DA)), we propose a score with a high contribution of basal levels of 17OHP, 21DF, testosterone, Androstenedione and 11 Beta-OH-Androstenedione, with a sensitivity/specificity of 100% towards the diagnosis of NCCAH.
Conclusion: We propose in addition to the gold standard ACTH test, a new score using different steroids at basal levels to ascertain the diagnosis of NCCAH with an excellent sensitivity.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology