098 - Use of Letrozole in a Patient with Peripheral Precocious Puberty. Ghufran S. Babar,MD MSc, Associate Professor of Endocrinology, Children's Mercy Hospital and Clinics. 3101 Broadway Blvd, Kansas City, MO 64111

BACKGROUND Precocious puberty is traditionally defined as the onset of secondary sexual development before the age of eight years in girls and nine years in boys (1). Precocious puberty could be central precocious puberty or peripheral (precocious pseudo) puberty (2). Central precocious puberty is gonadotropin-dependent, and involves the premature activation of hypothalamic-pituitary-gonadal axis. Peripheral precocious puberty is gonadotropin- independent. It is caused by production of sex hormones without the activation of pituitary-gonadotropin axis. The commonest cause for peripheral precocious puberty is functional ovarian cyst. Boepple PA, Crowley WF Jr. Precocious puberty. In: Reproductive Endocrinology, Surgery, and Technology, Adashi EY, Rock JA, Rosenwaks Z (Eds), Lippincott-Raven, Philadelphia 1996. Vol 1, p.989. Lee PA: Puberty and its disorders. Lifshitz F ed. Pediatric Endocrinology. 2003, New York: Marcel Dekker, 216-217

Background continued Small follicular cysts are commonly found in the ovaries of prepubertal girls. Most of these cysts resolve spontaneously. Occasionally, these cysts enlarge and continue to produce estrogen, causing premature feminization of females and appearance of sexual precocity. Autonomous ovarian cysts represent 2-5% of cases and can cause peripheral precocious puberty (3). Millar DM, Blake JM, Stringer DA, Hara H, Babiak C. Prepubertal ovarian cyst formation: 5 years' experience. Obs Gyn 1993 Mar;81(3):434-8.

CASE A 6 years and 2/10 months old Caucasian girl who presented with recent onset of breast development. There was no report of pubic hair development or onset of menstrual bleeding. She has history of ADHD, no family history of precocious puberty. Physical exam showed no dysmorphic features, Tanner 3 for breast and Tanner 1 for pubic hair. No café-au-lait spots, rest of the exam was normal.

CASE Initial work-up showed a normal Cortisol, ACTH and thyroid hormone levels DHEA-S less than 15 (0-149) LH less than 0.1 (0.0-2.7), FSH less than 0.1 (0.55-3.7), and Estradiol 297. Pelvic ultrasound showed: The right ovary is enlarged measuring 4.9 x 3 x 3.8 cm in size and is mostly replaced by a large cystic well-circumscribed structure measuring 4.4 x 3.1 x 3.2 cm. Left ovarian size was 2.5 x 1.1 x 1 cm.  Pubertal appearance of the uterus. No uterine mass (Figure: 1) Figure: 1

CASE MRI of the pelvis also confirmed the ovarian cyst (Figure: 2). She also had negative tumor markers for ovarian cancer and a negative skeletal survey. She was started on tablet Letrozole to block the estrogen production and prevent the pubertal progresion. (Figure: 2)

CASE On follow-up visit in 3 months there was no interval progression of the precocious puberty, the pelvic ultrasound showed a spontaneous resolution of the ovarian cyst (figure: 3). Repeat estradiol level: < 7 pg/ml. Letrozole was stopped. Subsequent follow-up in 4 months showed a sustained non-progression of puberty, no recurrence of the ovarian cyst. Figure: 3

Conclusion This case represents a unique case of the use of Letrozole in peripheral precocious puberty It helped to block the estrogen production The progression of peripheral puberty was stopped. Letrozole was stopped after the spontaneous regression of a functioning ovarian cyst and there has not been no recurrence of puberty even after one year of follow-up.