ESPE Abstracts

Background: Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by the overexpression of CYP19A1 at 15q21. Patients with AEXS manifest various clinical features associated with oestrogen excess; gynecomastia, hypogonadotropic hypogonadism, and advanced bone age are the most salient features in this condition.

Objective and hypotheses: The primordial treatment of the gynecomastia in patients with AEXS is surgical mastectomy, however long-term treatment with aromatase inhibitor for hypogonadotropic hypogonadism and short stature due to advanced bone age has not been established in children. We evaluated the effect of aromatase inhibitor for 2 years in a pubertal patient with AEXS.

Method: The patient was 10-year-old boy. Comparative genomic hybridization analyses using a microarray identified about 200 000 bp heterozygous deletions included several exons of the neighbouring genes DMXL2 and GLDN, which located upstream of the CYP19A1 start codon in familial gynecomastia (father, elder brother and the patient). Because of psychological distress caused by gynecomastia, the patient’s father and elder brother had both undergone mastectomies. Endocrine examinations showed decreased gonadotropin and testosterone levels, and oestradiol level remained undetectable. His bone age was significantly advanced with 13 years old nine months, and his predicted final height according to the growth-potential method was 150 cm. Because of his predicted final height, the patient was treated with an aromatase inhibitor.

Results: After 1 month of oral administration of 1 mg/day of anastrozole, the gynecomastia showed a tendency to improve and both LH/FSH (from 0.6/1.9 to 2.9/2.8 mIU/ml) and testosterone (from 19.5 to 389.6 ng/dl) levels were increased. Subsequently, 1 mg/day of anastrozole was continued every other day. His predicted final height was increased to 163 cm at 2-year evaluation. No adverse effects were evident during treatment.

Conclusion: 2 years of anastrozole treatment for pubertal AEXS patient with a poor predicted final height was safe and effective for the improvement of gynecomastia and predicted final height.

Funding: This work was supported by The Foundation for Growth Science 2013 in Japan.