Introduction. Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may serve as an additional criterion. Precocious puberty is divided in central precocious puberty and pseudoprecocious puberty. Central precocious puberty (GnRH dependent) occurs because of premature activation of hypothalamic-pituitarygonadal axis and activity of gonadotrophins. Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual steroids that are not the result of gonadotrophin activity. Objective. Objective of our study was to examine the etiology, clinical and laboratory manifestations of isosexual pseudoprecocious puberty in girls. Method. In the period between 1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty were studied at the Endocrine Department of the Institute of Mother and Child Health Care of Serbia. Initial evaluations included height measurement, staging of puberty, bone age assessment and pelvic ultrasound. Important diagnostic sonographic parameters of precocious puberty were the volumes of ovaries and uterus as well as ovarian structure. The initial hormonal evaluation included measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test was used to evaluate LH and FSH responsiveness (60 ?g/m2 LHRH- Relefact LHRH?, Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH stimulated LH and FSH were determined by immunoradiometric assay. Estradiol concentration was measured using the fluoroimmunometric assay. Results. Thirty-four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty were studied during the period of 9 years. Eleven girls presented with breast development, six with vaginal bleeding and seventeen with signs of puberty. On the basis of clinical signs, bone age, estradiol levels and LHRH test, premature the larche was diagnosed in eleven patients (32.4%), premature menarche in six (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%) presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed unilateral ovarian cysts in six patients and granulosa cell tumor in one. Elevated estrogen serum levels and failure of gonadotropin responses after gonadotropin releasing hormone were the classical findings in patients with isosexual pseudoprecocious puberty during the acute period of disease. In four patients, the cyst decreased spontaneously after several months, while in two patients, the cyst was removed by laparotomy. Surgical treatment was performed in a patient with granulosa cell tumor. Conclusion. Our work demonstrates that autonomous functional ovarian follicle cyst is the most often cause of isosexual pseudoprecocious puberty. Short period of observation is suggested because the cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor, as highly malignant tumor, should be removed as soon as diagnosis is established.
Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty
