Abstract 35

Increased extraglandular aromatization has been reported as a cause of gynecomastia. We studied two siblings with unrelated parents expressing clinical and biochemical evidence of aromatase excess. The affected male (propositus) developed gynecomastia at 8 years of age. At 13y his gynecomastia had progressed to Tanner stage V and his bone age was 17y. At 20y he presented lack of body hair, small penis size (6, 5×2, 0cm), normal pubertal testes and his height (161cm) was smaller than his target height (169cm). Exogeneous estrogen intake and adrenal or testicular tumor were ruled out. Testosterone levels were low (119-127ng/dL) and estradiol levels were very high (171-181pg/mL). His sister developed breasts at 8y and menarche at 10y. At 21y she had reached her target height (154cm) and presented with macrosmatia, irregular menstrual cycles, enlarged uterine volume (100-200cm3) and increased estradiol levels (237pg/mL). Aromatase hyperactivity explains the clinical and hormonal data in this family. Mutations in aromatase gene promoter have been described in Sebright and Campine roosters with feminizing feathering pattern. Therefore mutations in aromatase gene, which have not been described in humans yet, could be involved in this familial syndrome with elevated estradiol levels, gynecomastia and hypogonadism in males and premature thelarche in females.