Aromatase excess syndrome presenting with prepubertal gynecomastia in an Egyptian child with type 1 neurofibromatosis
A 4-year-old Egyptian boy was referred to our clinic for evaluation of bilateral asymmetrical gynecomastia which slowly increased in size over the past 6 months. He was known to have NF1, but had no other medical history of note. Family history was negative for breast malignancies, but positive for NF1 in the father and prepubertal gynecomastia in two of his brothers. Mental development was normal. No drugs or dermal applications were used. There was no history of galactorrhea. Physical examination showed a healthy-appearing boy with multiple café-au-lait spots with diameter > 1.5 cm [Figures and ]; axillary and inguinal freckling. His height was 115 cm (>97th percentile) and weight 20 kg (90th percentile).\nPalpation of the both breast revealed a firm mobile mass measuring approximately 6 cm in diameter in left and 4 cm in the right corresponding to a female Tanner B3 stage[] [], with tenderness on deep palpation. The right nipple-areola complex was also enlarged, measuring 1.5 cm compared to 1 cm on the left. There was no sign of galactorrhea and his testicular volume was 4 ml bilaterally. The penis was infantile and there was no pubic or axillary hair. Ultrasound examination of both breast showed retroareolar glandular tissue with normal aspects and swelling containing subcutaneous fat tissue. Bone was advanced by 3 years.[] An abdominal and testicular computed tomography scan excluded any estrogen-producing tumor. Routine serum/blood chemistry was normal. Chromosome analysis in cultured peripheral blood lymphocytes was also normal. Endocrinological testing revealed that the child had persistently raised levels of estradiol (E2; 33, 40, and 37 pmol/l; normal: 15-35) in the presence of undetectable T levels of < 0.1 nmol/l (9.1-27.8). Basal levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal (0.5 and 0.41 IU/l, respectively and 1.3 and 1.5 IU/l, respectively), with no change in response to stimulation by 100 mg of LH-releasing hormone intravenously. TSH, free thyroxine (FT4), and prolactin levels were normal. Genetic studies showed mutations of the CYP19A1 gene and presence of the allele (TTTA) 11 in a homozygous state and located in intron 4 of the CYP19A1 gene. Based on these findings, a diagnosis of AEXS was made. He was started on treatment with an aromatase inhibitor (tamoxifen 10 mg/day, orally). Our patient was seen 6 months after starting treatment. His growth velocity decreased from 7 to 5 cm per year and gynecomastia from 6 to 3 cm in diameter. E2 and T levels were near to normal levels. Our plan is to continue treatment and to follow-up every 6 months till improvement of gynecomastia.