6-Year-Old Girl With a Luteinized Follicular Ovarian Cyst and an Estradiol Level > 1,000 PG/ML

Background: Precocious puberty in girls is defined as onset of secondary sexual characteristics, such as breast development, before 8 years of age. To differentiate between central and peripheral precocious puberty, laboratory and imaging evaluation is helpful. When gonadotropins are low but estradiol is elevated, results may suggest a primary ovarian source of estrogen production. Small ovarian cysts are not uncommon, are benign and self-resolve. However, large ovarian cysts are rare, let alone ones requiring surgical removal. Clinical Case: A 6 year 7 month old girl presented with several days of breast tenderness and palpable bilateral breast tissue noted by her mother. There was no history of vaginal bleeding. There were no reported exposures to estrogen-containing products. Her mother reached menarche at age 14 years. The patient was born full term and was otherwise healthy. On exam, her height was at the 90-95(th) %ile (mid-parental height at the 95(th) %ile) and her growth velocity was 10.9 cm/yr. She had Tanner 2 breasts (1 cm breast bud on the left and 1.5 cm on the right), Tanner 1 pubic hair and no axillary hair, body odor, acne or café-au-lait macules. A bone age was read as 6 years at a chronological age of 6 years 7 months. A laboratory evaluation revealed an estradiol of 1,029 pg/mL (<15 pg/mL), LH <0.02 mIU/mL, FSH <0.09 mIU/mL, 17-hydroxyprogesterone (17-OHP) 410 ng/dL (<91 ng/dL), AFP 2.3 ng/mL (<6.1 ng/mL), beta-hCG <2 mIU/mL, TSH 2.41 mIU/L (0.5-3.2 mIU/L), and free T4 0.9 ng/dL (0.9-1.4 ng/dL). Pelvic ultrasound revealed a large unilocular cystic structure measuring 6.5 x 4.1 x 6.1 cm in the left adnexal region with no left ovary visualized. The right ovary appeared prepubertal. The uterus was prepubertal in appearance with endometrial thickness of 2 mm. Abdominal ultrasound showed no evidence of a suprarenal mass. A laparoscopic cyst resection was completed, given the risk of left ovarian torsion. Cytology was negative; pathology revealed a luteinized follicular cyst. Repeat labs in one month showed a prepubertal estradiol level of 6.7 pg/mL with LH 0.02 mIU/mL and FSH 0.38 mIU/mL. 17-OHP normalized to 29 ng/dL. Breast tissue had regressed. Conclusion: This case describes the rare finding of a large luteinized follicular ovarian cyst that required surgical removal in a 6-year-old girl in the setting of a significantly elevated estradiol level. Luteinized follicular cysts have been described in newborns, though rare. To our knowledge, this is the first described case of a luteinized follicular cyst in this patient’s age group. Laboratory and imaging evaluation should be considered in girls presenting with precocious puberty, despite the extent of thelarche, as the clinical examination does not always correlate with degree of estradiol elevation. This is especially important if clinical changes are acute and other features are consistent with puberty, such as rapid linear growth.