SAT-305 Hyperactive Behavioral Change during Combination Treatment of Aromatase Inhibitor and Recombinant Human Growth Hormone in Early Puberty Patient: A Case Report

Abstract

Aromatase inhibitor (AI) is a drug that blocks the converstion of androgens to estrogens, originally approved by FDA as a treatment of breast cancer in postmenopausal women. In several studies, it has been proposed that AI can be used as a off-label treatment to improve the final adult height in short pubertal boys by delaying growth plate closure, because that estrogen has an important role in pubertal growth spurt by promoting the closure of epiphyses, skeletal maturation in males as well as females. AI has been also introduced to be used for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts. In recent studies, AI appears effective in increasing final adult height, however, safety concerns also remain including androgenic adverse effect and vertebral deformities. Although that we experienced that there has been no major adverse effects in AI-treated pubertal boys as reported in other studies, we would like to introduce a case of pubertal boy showing hyperactive behavioral change when co-treated with AI and rhGH for short stature and early puberty. A 10 years and 2 months-old boy visited our clinic and his initial examination revealed as follows; height was 143.7cm (81th percentile) and weight was 45.3kg (89th percentile); secondary sexual characteristics of Tanner stage III. Bone age was assessed to be 13 years by TW3 method. He was diagnosed as ADHD in previous years, but not prescribed medicine because of well-controlled behavior. We diagnosed the patient as early puberty, and combination treatment of GnRH agonist and rhGH was started. After 10 months, GnRH agonist treatment was discontinued, and after-GnRHa AI treatment was started to slow down bone age progression and improve his height. We prescribed letrozole 2.5mg once a day. After 7 months, we discontinued AI because of his aggravated hyperactivity and uncontrolled aggressive behavior which was much more severe than before. We could not rule out the possibility of testosterone-mediated side effect. At that time, his height was 170.4cm with a gain of 26.7cm (chronological age of 13 years and 3 months). The progression of bone age was successfully suppressed during the treatment. After 1 years of completion, we checked his near-final height as 173.4cm. In conclusion, testosterone levels have been thought to be linked to aggression and violent behavior in adults and postpubertal adolescents in previous studies. Therefore, clinicicans should be aware of possible behavioral change in AI-treated early pubertal boys, which can be mainly induced by hypertestosteronemia, and further studies are needed to reveal other androgenic adverse effects.