Endocrine Abstracts

Background: Androgen excess frequently manifests in pre-pubertal children as premature adrenarche (PA). PA is characterised by the development of pubic and axillary hair, adult-type body odour in girls <8yrs and in boys <9yrs. PA may be a forerunner condition of polycystic ovary syndrome (PCOS), a complex metabolic disorder characterised by androgen excess. It is well established that women with PCOS have high risk of insulin resistance and frequently develop type 2 diabetes, dyslipidaemia, hypertension, and fatty liver disease. Importantly, androgens are identified as independent drivers to accelerate metabolic risk in PCOS. Whilst the link between PCOS and metabolic risk is well established, there is paucity of data on the risk for children with PA to develop metabolic dysfunction.

Objective: We conducted a systematic review and meta-analysis on metabolic disturbances in children with PA.

Methods: Published cross-sectional case/control studies were identified using Medline, Embase and Cochrane Library. Key outcome measures: Mean difference in anthropometric measures (height SDS, BMI SDS), indices of glucose metabolism (fasting insulin/glucose, HOMA-IR, HbA1c) and measures of lipid metabolism in children with PA compared to healthy controls.

Results: From 4640 records identified via electronic databases, 25 cross-sectional studies were selected, reporting on 823 children with PA and 707 healthy controls. Height SDS (mean difference [MD] 0.66; 95% confidence interval [CI₉₅] 0.36–0.95; I²=79%) and weight SDS (MD: 0.63; CI₉₅ 0.33 −0.93; I²=53%) were significantly higher in PA group. These findings persist with subgroup analysis by PA definition, sensitivity analysis for gender and risk of bias assessment. PA children also have higher fasting insulin levels than controls (MD: 15.04; CI₉₅ 5.27–24.81 pmol/l; I²=91%). Fasting glucose levels, HOMA-IR, mean serum glucose, mean serum insulin and HbA1c did not differ between PA and controls. Total cholesterol, LDL, HDL and VLDL were similar in both groups.

Conclusion: Our systematic review and meta-analysis with a pooled sample of more than 800 children with PA revealed higher fasting insulin levels but no other significant metabolic disturbances. However, we observed statistical and methodological heterogeneity. A unified approach in the assessment of metabolic risk in children with idiopathic early-onset androgen excess is needed, as well as long-term follow-up studies to identify children who might be at higher risk of developing metabolic dysfunction and PCOS.