Endocrine Abstracts

Introduction: Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by gain-of-function mutations in the aromatase gene (CYP19A1). It is characterised by pre or peripubertal gynaecomastia due to increased estrogen production from circulating androgens. Other features include advanced bone age, signs of testosterone deficiency such as small testis, high pitched voice and sparse facial hair in males, with macromastia and early puberty in females.

Case presentation: We report a 5 year old boy who presented with bilateral gynaecomastia and no features of pubertal development. He was otherwise healthy with no systemic disease or medications usage. His parents are nonconsanguineous and of Gambian descent. There was no family history of gynaecomastia in males nor macromastia or early puberty in females. At presentation, the patient was of lean build with height of 115.8 cms(+1.3SDS), weight of 19.5 kg (+0.3SDS) and BMI of 14.5 kg/m2 (-0.9SDS). He had bilateral breast tissue of B3-4 staging. Investigations showed 46XY karyotype, normal thyroid function and prolactin, undetectable FSH and LH, undetectable testosterone and androstenedione, with moderately elevated estradiol concentration for age (99 pmol/l). Urine steroid profile was normal. Ultrasound abdomen did not show any abdominal or testicular masses, except for few calcific foci in both testes consistent with testicular microlithiasis. Bone age was significantly advanced at 8.4 years with a chronological age of 5.1years (+4.6 SDS). Genomic analysis for disorders of sex development did not identify any pathogenic variant. Microarray CGH studies showed no evidence of copy number variant of the region including CYP19A1 and DMXL2 genes; further inversion analysis is pending. He was clinically diagnosed with AEXS with advanced bone age and raised estradiol concentration, having ruled out other causes of prepubertal gynaecomastia. The patient was managed with the aromatase inhibitor Letrazole, at dose of 2.5 mg once daily. He demonstrated an excellent initial response with undetectable estradiol concentration and reduction in breast size at 8 weeks.

Conclusion: This case highlights the rare diagnosis of AEXS (prevalence < 1in 1000000) in prepubertal child with gynaecomastia and advanced bone age. Treatment of this condition includes long term use of aromatase inhibitors with or without GnRH analogues or surgical mastectomy.