PLASMA 3-ALPHA-ANDROSTANEDIOL GLUCURONIDE IN PRECOCIOUS ADRENARCHE

The aim was to study 3alpha-androstanediol glucuronide (3AG) plasma levels and its relationship with 5-ene and 4-ene steroids in children with the benign form of precocious pubarche (precocious adrenarche). Sixty-five children with precocious adrenarche (PA), aged 3.6-8.2 yr (55 girls and 10 males) and 15 normal age-matched children were studied. We evaluated plasma androstenedione (A), dehydroepiandrosterone (DHA), its sulfate (DHA-S), testosterone (T), dihydrotestosterone (DHT), its glucuronide (DHTG), 3alpha-androstanediol (3Ad) and its glucuronide (3AG) in all subjects. All androgens are expressed as mean+/-SD. We found significantly higher plasma levels not only in glandular androgens but also in peripheral androgens (A, 2.4+/-1.5 nM vs 0.79+/-0.46 nM, p,0.001; DHA, 9.8+/-4.9 vs 2.7+/-0.76 ng/dl, p<0.001; DHA-S, 3.4+/-2 muM vs 2.4+/-0.65 muM, p<0.05; T, 0.74+/-0.5 nM vs 0.4+/-0.1 nM, p<0.001; DHT, 0.36+/-0.13 nM vs 0.12+/-0.05 nM, p<0.001; 3Ad, 0.13+/-0.1 nM vs 0.054+/-0.03 nM, p<0.001; DHTG, 0.5+/-0.3 nM vs 0.26+/-0.09 nM p<0.01). As far as the plasma 3AG levels are concerned we found significantly higher values in PA with respect to controls (1.17+/-0.7 nM vs 0.61+/-0.04 nM, p<0.01), suggesting that 3AG may be considered a marker of skin androgen utilization. 3AG plasma levels correlated better with serum A (p<0.002, r=0.42) and T (p<0.003, r=0.41) than with DHA (p<0.03, r=0.37), suggesting that both 4-ene and 5-ene androgens contribute to its production, but its plasma levels are better correlated with 4-ene than with 5-ene steroids. Furthermore 3AG plasma levels correlated with both 3Ad (p<0.01, r=0.4) and DHTG (p<0.001, r=0.47); no correlation was found with DHT, suggesting that in this condition 3AG may originate, in peripheral tissue either via the unconjugated pathway DHT -->3Ad-->3AG or via the conjugated pathway DHT-->DHTG-->3AG.