ESPE Yearbook of Paediatric Endocrinology

Brief summary: Steroid analysis using LC-MS/MS in association with clinical parameters may be used to develop a diagnostic score that could successfully differentiate premature pubarche (PP) from non-classic congenital adrenal hyperplasia (NCCAH), thereby obviating the need for ACTH stimulation testing.

Late onset, non-classic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency (21-OHD) should be ruled out in children with premature pubarche (PP). To this end, ACTH stimulation testing is currently used in these patients (1–3).

In this prospective study, the authors aimed to differentiate children with NCCAH from children with PP using a machine learning based approach to steroid profiles determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and clinical parameters obtained from a cohort of children with PP (n=97). A metabolic footprint was assigned for each patient using clinical data, bone age, and adrenal steroid levels recorded by LC–MS/MS. Separated in two sets, one training (n=58) and one validation (n=39), the authors developed a score using a mathematical machine learning model to identify patients with NCCAH in a cohort of children with PP. Based on selected variables, the prediction score was accurate (100%) at differentiating PP from late onset NCCAH patients. The most significant variables were 21-deoxycorticosterone, 17-hydroxyprogesterone and 21-deoxycortisol steroids.

These findings indicate that this new test has excellent sensitivity and specificity for the diagnosis of NCCAH, due to an ML approach. The authors suggest that if implemented as a routine test, it could eliminate the need for ACTH stimulation testing for the purpose of identifying NCCAH patients with PP. The results need further validation but these initial results are encouraging.

References: 1. Speiser PW, Dupont B, Rubinstein P, Piazza A, Kastelan A, New MI. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am. J. Hum. Genet. 1985; 37: 650–667. 2. Oberfield SE, Sopher AB, Gerken AT. Approach to the girl with early onset of pubic hair. J. Clin. Endocrinol. Metab. 2011; 96: 1610–1622. 3. Speiser PW, Arlt W, Auchus RJ, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103(11): 4043–4088.