MON-069 Uncontrolled Central Precocious Puberty Patient Against GnRH Agonist, After Showing Granuloma Formation and Sterile Abscess to Both Leuprorelin Acetate and Triptorelin Actate

Abstract

For more than 30 years, Gonadotropin-releasing hormone (GnRH) agonist has been the treatment of choice for central precocious puberty (CPP) to expect regression of secondary sexual characteristics, delayed menarche, and maximization of linear growth. There are several kinds of GnRH agonists such as leuprorelin, triptorelin, goserelin and histrelin, etc. In Korea, leuprolide acetate and triptorelin acetate are most common used drugs, and a monthly depot preparation is typically used for suppression of the HPG axis. Local complications related to GnRH agonists, including erythematous macules, granulomas, subcutaneous nodules, and sterile abscesses, occur in 10~15% of patients, and sterile abscesses have been known to occur in less than 2~3% of patients. In present case, we would like to introduce a case of CPP patient who was treated with GnRH agonist, but not suppressed and experienced recurrent vaginal bleeding, after showing granuloma formation and sterile abscess to both leuprorelin acetate and triptoreline actate. A 8.9 year-old girl visited our clinic with breast development and vaginal bleeding. On physical examination, she had enlarged breasts (Tanner stage 4) with pigmentation of the areola. Her height and weight was measured as 144.4cm (98th percentile) and 44.2kg (98th percentile) respectively. Her bone age was advanced as 12~12.6 years of age by TW3 method. Therefore, Leuprolide acetate (Lorelin depot®, Dongkook pharm) 3.75mg was administered to the patient every 4 weeks, and until the 6th injection, she exhibited no other complications. However, after 7th injection, the patient presented with granuloma and subcutaneous nodule at the left injection site and elevated hormone levels. Although that we switched to triptorelin acetate from 8th injection, the patient also showed a sterile abscess at the injection site. We switched from triptorelin acetate to leuprolide acetate again, however, after 2 months of the switch, the patient showed abrupt vaginal bleeding and elevated hormone levels. Therefore, after assumption of unsuppression of HPG axis, leuprolide acetate 3.75mg was administered every 2 weeks for 2 months. However, her vaginal bleeding occurred monthly and hormonal level was still unsuppressed, and also, the granuloma appeared again at the injection site. So, we discussed with her parents about her uncontrolled symptoms, and we discontinued the treatment. There are many theories about the cause of local complications of GnRH agonist, but the mechanism has still not been revealed. Further studies are required to identify the mechanism and the relationship between treatment effect and local complications, which could induce uncontrolled CPP.