Endocrine Abstracts

Introduction: Premature adrenarche (PA) is characterised by elevated adrenal androgens in pre-pubertal children presenting pubic/axillary hair, body odour, greasy hair, and transient growth acceleration. It is still unclear if children with PA are at increased risk of developing metabolic dysfunction or progressing to Polycystic Ovary Syndrome (PCOS) after puberty.

Aim: We launched a deep phenotyping study in children with PA from our large, multi-diverse population in the West Midlands. We report on body composition, patterns and severity of androgen excess and clinical cardiometabolic risk markers.

Design and Methods: Single-centre cross-sectional study in children with PA. We assessed body composition [clinical auxology and dual-energy absorptiometry (DEXA)], androgen profile (DHEAS [radioimmunoassay], androstenedione [A4] and testosterone [T] [liquid chromatography/tandem mass spectrometry]), fasting glucose, HbA1c and cholesterol/triglycerides.

Results: 42 PA children (35 girls and 7 boys) were included; precocious puberty and congenital adrenal hyperplasia were excluded. The age range was 4-9 years and 56% were of non-White background. Median BMI z-score was +1.2 (range -0.66; +3.72). All children had elevated DHEAS (median: 3.24 mcmol/l; range 1.1-8.8); in four girls, A4 was elevated above one-fold the upper normal limit; in all, T levels were within the normal range. Median HbA1c was 33 mmol/mol (range 27-39), fasting glucose was 4.8 mmol/l (range 4.3 – 5.3); fasting cholesterol and triglyceride levels were within normal ranges. Linear regression analysis showed a significant positive correlation between DHEAS and fasting glucose (r2=0.10; P = 0.042), which did not reach statistical significance after adjusting for BMI z-score. DHEAS correlated significantly with fat-free mass index (FFMI; r2=0.19; P = 0.013), but not with waist:hip ratio, fat mass index (FMI), % body fat or android/gynoid fat ratio. No association found between DHEAS and HbA1c, lipids, or BMI z-score, or BMI z-score with any metabolic parameters.

Summary and Conclusion: Our pilot cohort of PA children is characterised by DHEAS excess. Based on standard clinical parameters, a clear metabolic risk signature has not yet been recognised. Recruitment of children with PA and the establishment of matched control cohort is ongoing, which will include in-depth biochemical assessment such as untargeted metabolomics and multi-steroid profiling.