Early onset of puberty in young girls: an Italian cross-sectional study.

BACKGROUND: International literature and clinical practice have referred to Marshall and Tanner data to define the physiological age at onset of puberty. A study in the United States (1997) showed an anticipation in pubertal onset, whereas several European studies did not confirm this trend. AIM: To describe the onset of secondary sexual characteristics in a large Italian population of girls and to compare it to reference literature data. SUBJECTS AND METHODS: A cross-sectional study on 7311 2-14-yr-old girls who spontaneously requested a clinical evaluation for routine health check-up or acute illness by family pediatrician's offices in a northern Italian region (Lombardy), between September 2005 and November 2006. Trained family pediatricians performed a complete physical examination; pubertal status was evaluated following Tanner's criteria; breast development was assessed by palpation. RESULTS: Mean age of thelarche (B2), pubarche (PH2), menarche were 9.75, 10.09, and 12.49 yr, respectively. The prevalence of B2 and PH2 at ages 7-7.99 was 5.9% and 5.6%, respectively, at ages 8-8.99 was 15.5% and 13.8%, respectively. Mean time lapse from B2 to B3 and B2 to menarche was 1.46 and 2.74 yr, respectively. Mean age at menarche of our population and their respective mothers was almost identical. CONCLUSIONS: Our population presented earlier clinical signs of pubertal development than those defined by Marshall and Tanner. Mean age of menarche was not different in comparison to the previous generation. A different progression of pubertal development was found, in which the shift to B3 may have more clinical relevance.

Glucose turnover and insulin clearance after growth hormone treatment in girls with Turner's syndrome.

The study was performed to elucidate, by means of a euglycemic-hyperinsulinemic clamp, whether insulin sensitivity, lipid levels, posthepatic insulin delivery, and insulin clearance are impaired in girls with Turner's syndrome in the absence of previous treatment (T0) and after 6 (T6) and 12 (T12) months of growth hormone (GH) therapy (GHT). The study was performed in six girls with Turner's syndrome and eight healthy girls. We found that previously untreated girls with Turner's syndrome had a normal insulin activity on glucose metabolism. GHT progressively and significantly decreased hepatic insulin sensitivity. In fact, residual hepatic glucose release (HGR), which was 19.6 +/- 4.7 mg/m2. min at T0, doubled at T6 (39.3 +/- 5.1 mg/m2.min) and showed a threefold increase at T12 (68.7 +/- 10.8 mg/m2.min, P < .05 v T0). On the contrary, GHT did not show an appreciable influence on peripheral insulin sensitivity. Insulin clearance was higher in girls with Turner's syndrome than in control girls at T0 (30.0 +/- 2.8 v 20.2 +/- 1.1 mL.kg-1.min-1). It decreased to normal values at T6 (18.2 +/- 2.0 mL.kg-1.min-1, P < .05 v T0) and remained at normal levels at T12 (23.8 +/- 2.9 mL.kg-1. min-1). The posthepatic insulin delivery rate significantly increased at T6 and T12, suggesting increased insulin secretion. In conclusion, we found that insulin-stimulated glucose turnover was normal in girls with Turner's syndrome before therapy. One year of GHT was successful in stimulating the growth rate, but significantly decreased the insulin suppressibility on HGR with only slight changes in peripheral insulin sensitivity. In addition, an increase in the insulin posthepatic delivery rate and a normalization of insulin clearance were present, probably to counteract hepatic insulin resistance.

Final height in girls with central precocious puberty: comparison of two different luteinizing hormone-releasing hormone agonist treatments.

In order to evaluate the effects of two long-acting luteinizing hormone-releasing hormone agonists on growth, bone maturation and final height in girls with central precocious puberty, we analyzed growth data from 40 girls (15 treated with buserelin intranasal spray (group A), 15 treated with triptorelin depot im every 28 days (group B) and 10 untreated (group C)). Patients in group A started treatment when chronological age (CA) was 7.7 +/- 0.9 years, bone age (BA) was 10.2 +/- 1.1 years and height was 131.9 +/- 5.0 cm. Patients in group B started therapy when CA was 7.6 +/- 0.5 years, BA 9.8 +/- 1.0 years and height 133.2 +/- 7.6 cm. The diagnosis of untreated patients (group C) was made when CA was 7.2 +/- 0.9 years, BA 9.6 +/- 2.2 years and height 130.2 +/- 8.6 cm. Both luteinizing hormone-releasing hormone agonists appeared to control precocious puberty. Final height in group B (160.6 +/- 5.7 cm) was significantly higher than that of group A (153.2 +/- 5.0 cm: p < 0.05) and group C (149.6 +/- 6.3; p < 0.01), whereas the difference between groups A and C was not statistically significant. In group B a positive difference was observed between final height (160.6 +/- 5.7 cm) and target height (157.6 +/- 5.9 cm) (ns); on the contrary, in groups A and C, final height was lower than target height (155.5 +/- 5.3 and 156.4 +/- 1.3 cm, respectively), but only in group C the difference was statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous growth and pubertal development in Turner's syndrome with different karyotypes.

We studied spontaneous growth and pubertal development in 205 girls with Turner's syndrome, aged 1 month to 28.16 years, according to different karyotypes: 45,X (52%), X-mosaicism (12%), X-structural abnormalities (36%). Data on height, weight, height velocity, bone age and pubertal development were collected yearly in a mixed longitudinal and cross-sectional mode. Pelvic ultrasonography was performed in 133 patients, 46 of whom had contact breast thermography. Standards for height and height velocity (1-20 years) showed no differences when compared with other studies. Some differences were found when these data were subdivided by karyotype. In fact, X-mosaicism subjects had a pubertal growth spurt between 8 and 12 years of age. The spurt observed in this group cannot be justified by the more frequent presence of residual ovarian activity alone. It also appears in patients without ovaries and confirms the influence of a genetic factor on the X-chromosome. In spite of this spurt, the greatest final height was reached by 45,X subjects. X-mosaicism girls had more frequent spontaneous breast development linked to a higher percentage of visible ovaries. In this group the age of the first pubertal signs was similar to that of normal subjects and occurred much earlier than in the other groups.

Effect of estrogen replacement therapy on bone mineral content in girls with Turner syndrome.

Because a close relationship between estrogen deficiency and osteoporosis has been proven, it is possible that lifelong estrogen deficiency might be the cause of osteopenia in Turner syndrome. This study was done to characterize the effect of estrogen therapy on bone mineralization in girls with Turner syndrome. Radial bone mineral content values were found to be below the 95% normal confidence interval in 44 of 49 untreated patients, aged 10.82 +/- 3.45 years. An inverse correlation was found between the patients' ages and their delta bone mineral content values. The effect of beginning estrogen treatment early or late was studied in 16 girls who started the treatment before and 11 who started after age 12. Although they were still deficient compared with controls, the first group had better mineralization than the second (P = .0005). Finally, nine patients were followed prospectively during replacement therapy; their bone mineral content delta values changed significantly (P = .02) during the follow-up period (3.17 +/- 0.33 years), but the bone mineral content did not normalize. Our data show that estrogen deficiency per se does not cause osteoporosis in young girls with Turner syndrome. In fact, estrogen therapy prevented bone loss but failed to normalize the low bone mineral content values. Early treatment is preferable because it reduces the bone density deficit present in untreated patients.

Hormonal and psychologic assessment in LLA patients after bone marrow transplant.

Four adolescent males were submitted to hormonal and psychological evaluation 3-8 years after bone marrow transplant. All presented testicular failure, two were submitted to orchiectomy. Androgen replacement therapy was begun at 13 yr 7 mo-17 yr. A psychological evaluation has been performed. Orchiectomy and insertion of artificial testicles do not seem to have affected patients' psychological situation. Individual differences have been found due to many causes.

Echocardiographic diagnosis of congenital bicuspid aortic valve in gonadal dysgenesis.

Among the gonadal dysgenesis, Turner's syndrome (T.S.) is often associated with cardiovascular malformations, mainly of the aorta. In order to assess noninvasively the incidence of those abnormalities we have evaluated 36 consecutive female patients (pts) with gonadal dysgenesis, mean age 13.3 +/- 2 years, range 3-24 years, without a prior history of cardiovascular disease, by clinical examination chromosomal karyotyping, 12 leads electrocardiography (ECG), and by Time Motion (TM) and Two-Dimensional (2D) Echocardiography (Echo). The following parameters were considered: presence of an auscultatory systolic ejection click (SEC); evidence of a bicuspid aortic valve (BAV); aortic valve stenosis (AVS); aortic valve eccentricity index (AVEI); left ventricle wall hypertrophy (LVWH). 9 pts out 36 (25%) presented a BAV at the 2D Echo; 8 pts out of 36 (22%) presented a SEC, 3/9 (33%) mild AVS, 2/9 (22%) displayed AVEI on TM study and 3/9 (33%) had LVWH. These findings indicate that an isolated BAV is present in a high percentage of pts with gonadal dysgenesis, more than before suspected. Echocardiography shows to be particularly useful and reliable in the assessment of that abnormality.

Gynaecomastia and premature thelarche in a schoolchildren population of northern Italy.

The prevalence and incidence of gynaecomastia and thelarche have been studied in pre-school children and school children belonging to different socio-economical classes in two Northern Italian Cities: Milano and Mantova. The children selected underwent three clinical examinations in their own school by the same examinator. The highest prevalence (36.6%) of breast enlargement was observed in nursery children until 2 years of age in Milano. Age and sex specific incidence rates were higher in Milano than in Mantova except in boys 11-14 years old. Assumption of drugs which might induce gynaecomastia thelarche was excluded. Relative risks calculated for veal and chicken must suggest that these are not relevant in the etiology of breast enlargement.

Correlation of gonadal function with histology of testicular biopsies at treatment discontinuation in childhood acute leukemia.

Testicular open-wedge biopsy was performed in 35 children in complete remission from acute lymphoblastic leukemia without clinical signs of leukemic testicular infiltration at the time of treatment discontinuation. Histological investigation showed thickening of the tunica propria of the seminiferous tubules in 13 of 35 patients. In 5 of 35 patients, the tubular fertility index was markedly reduced; in 5 of 6 pubertal patients, decreased spermatogenesis or aplasia of germinal epithelium was observed. Histologic damage was found mainly in the germinal cells both in patients treated with cytosine arabinoside and cyclophosphamide and in those treated with antiblastic drugs not considered damaging to the gonads. The extent of impairment was independent of age at start of treatment. On the other hand, endocrinological investigation carried out at the crucial moment of treatment suspension showed normal hypothalamic-hypophyseal-gonadal function as well as normal anthropometric data, bone age, and pubertal stage in the majority of patients. Testicular leukemia was found in only one patient (2.8%) whereas three children with negative testicular biopsies had testicular relapses within 7 months. Therefore, in view of the limits of light microscopy in diagnosing leukemic infiltration at treatment discontinuation, we propose the use of more sophisticated techniques, possibly within 6 months of suspension of therapy.

[Late reattribution of sex: a clinical example]. / Riattribuzione tardiva di sesso: un caso clinico esemplificativo.

A female patient affected by congenital adrenal hyperplasia, has been brought up as a male till five and half year old. After exact diagnosis has been made, a complete psychological evaluation has suggested the possibility of a change in the rearing sex. We briefly summarize the psychological, medical, legal aspects of this late sexual reattribution. After a five-years follow up, results may be considered satisfactory.