Endocrine 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 8th 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 standard clinical cardiometabolic risk outcomes from our initial recruits.

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).

Results: 20 PA girls were included; precocious puberty and congenital adrenal hyperplasia were excluded clinically and biochemically. The age range is 5–8 years and 25% are of non-White British background. Median BMI z-score was +1.36 (range −0.5 – 2.55). All girls had elevated DHEAS (median: 3.14 μmol/L; range 1.3–5.6); 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 5 mmol/L (range 3.5–5.3); fasting cholesterol and triglyceride levels were within the normal range. Linear regression analysis showed a weak positive correlation between DHEAS and HbA1c (R2 0.25). No association was found between DHEAS and fasting glucose, 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. An unfavourable metabolic signature based on standard clinical parameters was not 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.