ESPE Abstracts

Background: Ovarian dysfunction is one of the most common features of Turner syndrome (TS). Oocyte apoptosis is accelerated from early fetal life, more typical for 45,X karyotype. Hypergonadotropic hypogonadism (HH) is characteristic manifestation of dysgenetic ovaries, and estrogen replacement therapy (ERT) is standard for delayed puberty. Development of ovarian follicles is largely under FSH control, and possible ovarian hyperstimulation of elevated FSH in TS may be discussed. We present a 14.5-year-old girl with TS, developing ovarian cyst during ERT, having an impact on the pubertal picture and growth hormone (GH) therapy response.

Case report: TS was diagnosed prenatally based on karyotype (45,X) and confirmed postnatally in the girl. Based on PCR analysis, presence of the SRY gene and other Y-linked genes was excluded. The girl showed multisystem clinical picture of TS: severe cystic hygroma, horseshoe kidney with hydronephrosis of right kidney, congenital dislocation of hip joint, bicuspid aortic valve, coronary micro fistula, clitoral hypertrophy, hearing impairment, autoimmune thyroiditis from age of 3.5 years. rGH therapy began at 2.5 years (htSDS=-3.3). At 11y (bone age 11-11.5), transdermal ERT was initiated due to HH (FSH 75.9 mIU/ml, breast development B1) with 0.12 ug/kg/d dose. At age 12.4 years, bleeding from uterus occurred. Her status was as follows: B4, US mature uterus volume, endometrial thickness 7 mm, invisible ovaries, E2 17 pg/ml, FSH 12.9, LH 5.41 mIU/ml. Because of the next bleedings, at 12.8 years, progesterone was added with ongoing ERT dose 0.11 μg/kg/d. After 9 months, anechoic cystic lesion (22 × 18 mm) in the right ovary was diagnosed on US. E2 was elevated 287 pg/ml, and the bone age 14. The estrogen/progesterone therapy was stopped. The bleeding became almost regular despite the lack of ERT. At 14y, breast development was B5, E2 persistently elevated - 353 pg/ml, AMH 0.14 ng/ml, gonadotropins were unexpectedly normal (FSH 2.7, LH 7.74 mIU/ml), ovarian cyst was still present. At 14.5y, the rGH was stopped by height of 141 cm.

Conclusion: The rapid, surprisingly good response to low-dose ERT could be the effect of individual high sensitivity to estrogens and/or persistent/recurrent ovarian cyst. The ovarian cyst has to be explained by further imaging methods (MRI) and/or by more invasive method (laparoscopy). The unsatisfactory final height could be caused by a functioning ovarian cyst and persistently high levels of E2, but also due to the multiorgan disorders in this girl.