SAT-304 Unexplained Asymptomatic Hyperestrogenism in Central Precocious Puberty Patient Treated with Gonadotropin Releasing Hormone Agonist

In Central precocious puberty(CPP), the gonadotropin-releasing hormone(GnRH) agonist competes with LHRH in the pituitary gland to desensitize and downregulate the response of gonadotropin-releasing hormone receptors, effectively inhibiting the secretion of sex hormones in the gonad to prepubertal levels. During the treatment, the bone age progression is slowed, the progression of secondary growth is stopped, and the secretion of sex hormones is maintained as prepubertal levels. We report a case of CPP patient who was treated with GnRH agonist, but abnormally elevated in estradiol level without changes in FSH and LH levels, and slowly normalized without any other abnormal clinical symptoms or laboratory findings. A 5 year and 10 months old girl visited our clinic with breast development which was examined as Tanner stage 2-3. Anthropometric datas were as follows: Her height was 127.3 cm(100th percentile), body weight was 29kg(100th percentile), and BMI was 17.9 kg/cm(2). Her bone age was asessed to be 9.7 years by TW3 method. In the abdominopelvic ultrasonography, her uterus showed a pubertal status and no other abnormal findings were noted. LHRH stimulation test showed a pubertal response (peak LH level: 12.1 IU/L after 30min). She was confirmed as central precocious puberty, but brain MRI could not be perfomed due to refusal of the patient’s parents. Suppressive treatment was initiated with leuprorelin acetate 3.75mg(Lorelin depo, Dongkuk pharm). There was no further progression of secondary sexual characteristics after the treatment, and we noticed the downregulation of gonadotropin(FSH,LH) and estradiol in initial follow up hormonal assessment. However, second follow up study which was perfomed after 6 months of the treatment showed a feature of peripheral precocious puberty (FSH:1.0 IU/L(normal<2), LH:0.5 IU/L(normal<0.3), Estradiol: 68.6 pg/mL(normal<10)). There was no changes in secondary sexual characteristics of the patient, and no specific abnormal finding was found in her pelvic ultrasonography. On consecutive serial follow up studies, only the estradiol level was elevated gradually, and reached 162.2 pg/mL after 12 months of the treatment. There was no estrogenic effect such as acceleration of height gain, progression of secondary sexual characteristics, uterine enlargement, or rapid bone age progression. The duration of elevated hormonal status of the estradiol was nearly 48 months. Bone age was advanced from 9.7 to 10.4 years in this period. No abnormal skin lesion including café au lait spot was appeared. However, after this period, estradiol level was gradually decreased and normalized on consecutive follow up studies. In conclusion, estrogen elevation could be shown during the GnRH agonist treatment in CPP patients, however, there is an uncommon possibility of rising and normalizing estrogen levels without evidence of disinhibition in being-treated CPP patients.