Cardiometabolic outcomes in girls with premature adrenarche: a longitudinal analysis of typical vs. exaggerated presentations.

Objectives: To evaluate cardiometabolic risk factors in girls with premature adrenarche (PA), with a specific focus on outcomes based on adrenal androgen levels (typical vs. exaggerated adrenarche).

Methods: Eighty-four girls with PA were followed from diagnosis to mid-puberty. Clinical, biochemical, and hormonal parameters were assessed at both time points. Participants were stratified based on dehydroepiandrosterone sulfate (DHEAS) levels: typical PA (40-130 μg/dL) and exaggerated adrenarche (>130 μg/dL). Age- and sex-matched controls (n=58) were included for pubertal comparisons.

Results: At baseline, 25 % of PA girls were overweight/obese, and 22 % had elevated HOMA-IR. Exaggerated adrenarche was present in 19 % of subjects. By puberty, overweight/obesity prevalence rose to 33.3 %, with significant increases in fasting insulin, HOMA-IR, and declines in insulin sensitivity indices (QUICKI, FGIR). Comparisons with controls revealed significantly higher BMI, waist circumference, and insulin resistance among PA girls. However, there were no significant metabolic differences between exaggerated and typical PA groups, except for a higher waist circumference in the exaggerated group.

Conclusions: Elevated mid-childhood DHEAS does not independently predict worsened metabolic outcomes by puberty. Baseline adiposity, not androgen level, is the principal determinant of insulin resistance and cardiometabolic risk in PA. Lifestyle interventions targeting weight management are crucial in mitigating future risk.