ESPE Abstracts

Introduction: Early-onset androgen excess commonly presents in pre-pubertal girls as premature adrenarche (PA). Girls with PA have clinical signs of androgen excess, such as pubic/axillary hair, body odour, greasy hair, and moderately elevated adrenal androgens before their 8^th birthday. There is conflicting evidence if girls with PA are at higher risk to have or develop metabolic dysfunction, or progress to developing Polycystic Ovary Syndrome (PCOS), the most common complex metabolic condition in women of reproductive age.

Aim: We have launched a deep phenotyping study in children with premature adrenarche recruiting from our large, multi-diverse population. Herein, we report initial data on body composition, androgen load and standard clinical cardiometabolic risk outcomes in our pilot cohort.

Design and Methods: Single-centre cross-sectional phenotyping study. We report on standard auxology and fasting biochemical parameters, including androgen profile (DHEAS [RIA], androstenedione [A4] and testosterone [T] [LC/MSMS]), fasting glucose, HbA1c and lipids (cholesterol, triglycerides). Body composition was assessed by dual-energy absorptiometry (DEXA).

Results: 41 PA children (34 girls and 7 boys) were included; precocious puberty and congenital adrenal hyperplasia were excluded clinically and biochemically. The age range is 4-9 years and 56% were of non-White British 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 limit of normal; in all, T levels were within the limit of normal. 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 the normal range. 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 fat mass index (FMI), percent body fat or android/gynoid fat ratio. No association was found between DHEAS and HbA1c, DHEAS and lipids, DHEAS and BMI z-score, or BMI z-score with any metabolic parameters.

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