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To explore the independent role of age at menarche on menstrual abnormalities among adolescents. The present study was a multicenter cross-sectional study on a large sample (n = 3782) of Italian girls aged 13–21 y attending secondary school who already had menarche. Girls were asked to fill in a questionnaire on menarcheal age and menstrual features during the latest three menses. The gynecological age was computed as the difference between age at the survey and the age at menarche. Main outcome measures were: prevalence of oligomenorrhea, polymenorrhea, menstrual cycle irregularity, abnormal bleeding length and dysmenorrhea. Irregularity in the recent past and since menarche was also studied. Multiple logistic models were used to identify any independent association between each abnormal feature and age at menarche or gynecological age. Adjusted ORs and 95%CI were performed. After adjusting for covariates, menarcheal age was not independently associated with polymenorrhea (OR = 0.81; 95%CI 0.63–1.04), oligomenorrhea (OR = 1.16; 95%CI 0.94–1.43), menstrual cycle irregularity (OR = 0.99; 95%CI 0.86–1.14), abnormal bleeding length (OR = 0.96; 95%CI 0.87–1.06) and dysmenorrhea (OR = 1.03; 95%CI 0.85–1.24). The multivariate analysis suggests that the higher prevalence of oligomenorrhea and menstrual cycle irregularity among the girls who were older at menarche might be purely explained by their younger gynecological age. No evidence of any independent influence of age at menarche on menstrual abnormalities among young girls was shown by the investigation. The findings suggest that, after menarche, adolescent girls’ menstrual health should be checked to monitor the endocrine system maturation and to early intercept latent disorders becoming symptomatic.

Objective The main aim of this study was to verify whether the secular trend stopped in Italy by comparing the results of a 1990–2000 birth cohort versus a 1980–1990 birth cohort of Italian young women. The results were used to speculate about age at menarche as adaptive response to non-genetic factors. Methods In 2016, a study was set on 413, 18-to-26 year-old women (1990–2000 birth cohort) attending two Italian Universities by web-based, self-reported questionnaires. Previously in 2000, a research including 3,783 high school female students (1980–1990 birth cohort) was led. The age at menarche distribution was performed by Kaplan-Meier analysis. The comparison between the findings of the two birth cohorts was performed by Wilcoxon sum-rank test. Mixed models analysis was applied to evaluate the effect of cohort and socio-economic status on age at menarche. Results 1990–2000 cohort's age at menarche median was 12.44y (95%CI 12.37; 12.59y). There was no significant difference with age at menarche of the previous cohort (p = 0.56). Consistently, the advance of age at menarche in comparison to the mothers' one was not significantly different between the two cohorts (-0.27y±0.10y vs -0.25y±0.03y, p = 0.33). The socio-economic level was not significantly associated with menarcheal age. Conclusions The findings of this study confirm that, like in other developed countries, the advance of age at menarche has stopped in Italy, consistently with the stop of the improvement of socio-economic conditions. Further studies are needed to explore the differential effect of each non-genetic factor to outline future scenarios of human sexual maturation. Trial registration the Comitato Etico per la Sperimentazione Clinica (CESC) della Provincia di Padova of the Veneto Region (Italy), n°3993/U16/16., Public Health; Epidemiology; Women's Health; Obstetrics & Gynecology; Age at menarche; Secular trend; Adolescents' health; Decline.

This population-based study on school-aged girls aimed to estimate the rate of peri-menstrual headache, evaluate headache pain pattern during the menstrual cycle, and verify its relationships with physical, psychosocial and life-style factors. The students (n = 4973) fulfilled a self-administered questionnaire on demographic and behavioral characteristics, menarche, menstrual pattern and features including headache and dysmenorrhea. The prevalence of headache and the mean pain intensity score at the three menstrual cycle phases (premenstrual, menstrual, in-between period) were estimated, both overall and by gynecological year. Furthermore, the prevalence of three different patterns of headache (peri menstrual/mid-cycle/acyclic) was evaluated, together with the mean pain intensity score. The overall prevalence of headache at least once at any time during the menstrual cycle was 64.4%. At multivariable logistic analysis, gynecological age (OR 1.07; 95%CI 1.03–1.12), middle social level (1.24; 1.01–1.55, compared to high social level), physical activity (0.67; 0.51–0.89), oral contraceptive use (1.34; 1.04–1.73) and dysmenorrhea (2.30; 1.54–3.42) were significantly associated with headache. Among girls with headache, 83.4% had peri-menstrual headache (44.6% premenstrual, 38.8% menstrual), 3.5% mid-cycle headache and 13.2% acyclic headache. The gynaecological age and dysmenorrhea were significantly associated with the headache pattern (p = 0.03 and p

Premise: Healthcare professionals need updated information about what is the range of “normal” variation of menstrual cycle features to support young girls and their parents in managing reproductive health, and to detect diseases early. Materials and Methods: This cross-sectional study aimed to provide an updated picture of age at menarche and main menstrual cycle characteristics and complaints in an Italian population-based sample of 3,783 adolescents attending secondary school. Girls filled in a self-administered anonymous questionnaire including questions about demography, anthropometry, smoking and drinking habits, use of contraceptive, socioeconomic status, age at menarche, menstrual pattern, and physical/psychological menstrual complaints. Mean age at menarche and prevalence of polymenorrhea (cycle length < 21 days), oligomenorrhea (cycle length > 35 days), irregularity, dysmenorrhea, and of physical/psychological complaints were computed. Factors associated with age at menarche and menstrual disturbances were explored by using multiple logistic models. Results: The girls’ mean age was 17.1 years (SD 1.4 years) and the mean age at menarche was 12.4 years (SD 1.3 years); menarche occurred with two monthly peaks of frequency in July–September and in December–January (P < 0.0001). Age at menarche was significantly associated with geographic genetics (as expressed by parents’ birth area), mother's menarcheal age, BMI, family size, and age at data collection. The prevalence of polymenorrhea was about 2.5%, oligomenorrhea was declared by 3.7%, irregular length by 8.3%, while long bleeding (>6 days) was shown in 19.6% of girls. Gynecological age was significantly associated with cycle length (P < 0.0001) with long cycles becoming more regular within the fourth year after menarche, while frequency of polymenorrhea stabilized after the second gynecological year. Oligomenorrhea and irregularity were both significantly associated with long menstrual bleeding (adjusted OR = 2.36; 95% CI = 1.55-3.60, and adjusted OR = 2.59; 95% CI = 1.95-3.44, respectively). Conclusions: The findings of the study support the levelling-off of secular trend in menarche anticipation in Italy and confirm the timing in menstrual cycle regularization. The study provides updated epidemiological data on frequency of menstrual abnormalities to help reproductive health professionals in managing adolescent gynecology.

OBJECTIVE: Excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed individuals. Turner's syndrome (TS) patients are a population at risk since they have reduced glucose tolerance (GT) spontaneously and because they are usually treated with high doses of GH. DESIGN AND METHODS: The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of TS patients treated with GH for a period of 6 years. Forty-seven TS girls were included in the study. GH was administered at a mean weekly dosage of 0.35 mg/kg, injected subcutaneously over 6-7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICK-I). RESULTS: No significant increase of impaired GT was observed in the patients during the follow-up period, while a reduced IS was detected. IS in TS patients was already lower than in prepubertal controls (P

Dysembryoplastic neuroepithelial tumors (DNTs) are mainly benign cortical lesions composed of glial and neuronal elements. DNTs accounted for 0.6–07% of pediatric brain tumors. Clinically these tumors are usually associated with chronic epilepsy in adolescents and adults. We report a case of six-year-old boy who presented drug-resistant complex partial seizures whit neurological and intellectual integrity, but a mild attention deficit. MRI disclosed a subcortical lesion, located on the left the temporal lobe. The pathological tissue was hyperintense on both T1 and T2-weighted images; CT showed very well intratumoral calcifications. These neuroradiological findings suggested a differential diagnosis with extraventricular neurocytoma and ganglioglioma. The child underwent surgery; the histological examination diagnosed a complex DNT (1st grade of WHO classification). At follow-up after 6 months, he was seizure-free; the neurological examination was normal.

To define the role of somatostatin and dopamine in TSH suppression induced by L-thyroxine, 16 children (12 F, 4 M) on suppressive doses of L-thyroxine (3-4 microg/kg/day) for endemic goiter were studied. Firstly a conventional TRH test was performed in all subjects, in order to evaluate TSH, PRL and GH (basal study). A week later a second TRH test was carried out; one hour before the test, however, group A (9 patients) was given 60 mg pyridostigmine bromide po (pyridostigmine study) and group B (7 patients) 10 mg metoclopramide po (metoclopramide study). In the basal study, TSH was suppressed in both groups and levels did not increase following TRH administration, while PRL increased significantly and GH levels remained stable. In the pyridostigmine study, TSH levels did not increase following TRH administration, while PRL and GH levels were both significantly raised. In the metoclopramide study, TSH and GH levels were not raised following TRH administration, while a significantly greater increase of PRL was observed. In conclusion, suppressive doses of L-thyroxine inhibit the TSH response to TRH, while they do not seem to affect GH and PRL secretion. Somatostatin and/or dopamine do not seem to play a significant role in the L-thyroxine-induced TSH suppression.

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/ kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.

Hypochondroplasia is an autosomal dominant skeletal dysplasia characterized by disproportionate short stature. A mutation (N540K) in the fibroblast growth factor receptor 3 (FGFR3) gene was described in some patients with this condition. The aims of the study were to identify the frequency of the FGFR3 gene mutation, to define the salient clinical and radiological abnormalities of the affected subjects, and to verify the contribution of molecular findings to the clinical and radiological definition of hypochondroplasia. Based on the most common radiological criteria, we selected 18 patients with a phenotype compatible with hypochondroplasia. Height, sitting height, and cranial circumference were measured in all patients. Radiographs of the lumbar spine, left leg, pelvis, and left hand were also obtained. The presence of the N540K mutation was verified by restriction enzyme digestions. Half of our patients carried the N540K mutation. Although similar in phenotype to the patients without the mutation, they showed in addition relative macrocephaly. The association of the unchanged/narrow interpedicular distance with the fibula longer than the tibia was more common in patients with gene mutation. Although we did not find a firm correlation between genotype and phenotype, in our study the N540K mutation was most often associated with disproportionate short stature, macrocephaly, and with radiological findings of unchanged/narrow interpedicular distance and fibula longer than tibia.

Pseudohypoparathyroidism (PHP) is a heterogeneous disease characterized by PTH resistance and classified as types Ia, Ib, Ic, and II, according to its different pathogenesis and phenotype. PHP-Ia patients show Gsalpha protein deficiency, PTH resistance, and typical Albright hereditary osteodystrophy (AHO). Heterozygous mutations in the GNAS1 gene encoding the Gsalpha protein have been identified both in PHP-Ia and in pseudopseudohypoparathyroidism (PPHP), a disorder with isolated AHO. A single GNAS1 mutation may be responsible for both PHP-Ia and PPHP in the same family when inherited from the maternal and the paternal allele, respectively, suggesting that GNAS1 is an imprinted gene. To evaluate whether molecular diagnosis is a useful tool to characterize AHO and PHP when testing for Gsalpha activity and PTH resistance is not available, we have performed GNAS1 mutational analysis in 43 patients with PTH resistance and/or AHO. Sequencing of the whole coding region of the GNAS1 gene identified 11 mutations in 18 PHP patients, eight of which have not been reported previously. Inheritance was ascertained in 13 cases, all of whom had PHP-Ia: the mutated alleles were inherited from the mothers, who had AHO (PPHP), consistent with the proposed imprinting mechanism. GNAS1 molecular analysis confirmed the diagnosis of PHP-Ia and PPHP in the mutated patients. Our results stress the usefulness of this approach to obtain a complete diagnosis, expand the GNAS1 mutation spectrum, and illustrate the wide mutation heterogeneity of PHP and PHP-Ia.

After an analysis of the endocrine factors which contribute to testis descent, guidelines are given for gender assignment in newborn with bilateral cryptorchidism, with or without ambiguous external genitalia.

As rãs são usadas como modelos experimentais alternativos no estudo da nocicepção, tanto pela simplicidade do seu tecido nervoso como por permitirem uma abordagem filogenética sobre o tema. Um desses modelos é a secção do nervo isquiático (SNI), o qual simula os sintomas clínicos do “membro fantasma”, uma condição que ocorre nos humanos após amputação ou secção completa da medula espinal. Em mamíferos, a SNI aumenta o metabolismo da glicose no sistema nervoso central, e o lactato é uma fonte energética para as células nervosas. Porém é desconhecido se essa é a situação em gânglio da raiz dorsal (GRD). Como a glicose é o principal substrato energético para o tecido nervoso de rãs, e a concentração plasmática de lactato está aumentada nesses animais em distintas situações, a rã-touro Lithobates catesbeianus foi usada para demonstrar os efeitos da SNI sobre a captação de 1-[14C] 2-deoxi-D-glicose (14C-2-DG), na presença e ausência de lactato, em GRD e medula espinal. Foram demonstrados ainda os efeitos dessa condição experimental sobre a formação de 14CO2 a partir de 14C-glicose e 14C-L-lactato, e a concentração plasmática de glicose e lactato. A captação de 3-O-[14C] metil-D-glicose (14C-3-OMG) foi usada para demonstrar a relação tecido/meio estável da glicose nessas condições. A captação de 14C-2-DG aumentou três dias após a SNI, sem qualquer alteração na captação de 14C-3-OMG. O aumento foi reduzido quando o lactato foi acrescentado ao meio de incubação. A taxa de oxidação da glicose e do lactato não modificou após SNI, mas houve redução na concentração plasmática de glicose e lactato. Assim, a SNI aumenta o metabolismo da glicose no GRD e medula espinal de rãs. Os efeitos do lactato sobre essa captação sugerem o uso da glicose na via glicolítica após a SNI. Frogs have been used as an alternative model to study pain mechanisms because the simplicity of their nervous tissue and the phylogenetic aspect of this question. One of these models is the sciatic nerve transection (SNT), which mimics the clinical symptoms of “phantom limb”, a condition that arises in humans after amputation or transverse spinal lesions. In mammals, the SNT increases glucose metabolism in the central nervous system, and the lactate generated appears to serve as an energy source for nerve cells. An answerable question is whether there is elevated glucose uptake in the dorsal root ganglia (DRG) after peripheral axotomy. As glucose is the major energy substrate for frog nervous tissue, and these animals accumulate lactic acid under some conditions, bullfrogs Lithobates catesbeianus were used to demonstrate the effect of SNT on DRG and spinal cord 1-[14C] 2-deoxy-D-glucose (14C-2-DG) uptake in the presence and absence of lactate. We also investigated the effect of this condition on the formation of 14CO2 from 14C-glucose and 14C-L-lactate, and plasmatic glucose and lactate levels. The 3-O-[14C] methyl-D-glucose (14C-3-OMG) uptake was used to demonstrate the steady-state tissue/medium glucose distribution ratio under these conditions. Three days after SNT, 14C-2-DG uptake increased, but 14C-3-OMG uptake remained steady. The increase in 14C-2-DG uptake was lower when lactate was added to the incubation medium. No change was found in glucose and lactate oxidation after SNT, but lactate and glucose levels in the blood were reduced. Thus, our results showed that SNT increased the glucose metabolism in the frog DRG and spinal cord. The effect of lactate on this uptake suggests that glucose is used in glycolytic pathways after SNT.

A total of 478 patients, mean age 15.5 (3.6-25.3) years, suffering from Turner's syndrome, were studied in order to determine the frequency of autoimmune thyroiditis, which is defined as the presence of antithyroid antibodies (AT-Ab) and typical ultrasound findings. We found 106 (22.2%) patients positive for AT-Ab and of those 49 (10%) also had positive ultrasound findings, and were therefore considered to be affected by thyroiditis. This frequency is significantly higher (p < 0.001) than that seen in the normal population. Goitre was detected on clinical examination in only 16 (33%) and by ultrasound in 19 (39%) patients. Hormonal evaluation showed that 17 patients were euthyroid, 27 had compensated hypothyroidism, 2 were hypothyroid and 3 were in a hyperthyroid phase. Clinical signs or symptoms of hypothyroidism were absent in all hypothyroid patients. In patients with thyroiditis, neither a higher frequency of malformations and autoimmune diseases nor a correlation with karyotype, oestrogens or growth hormone therapy was found.Antithyroid antibodies, thyroiditis, thyroid hormones, thyroid ultrasound, Turner's syndrome G Radetti, Department of Paediatrics, Regional Hospital of Bolzano, via L Boehler 5, 39100 Bolzano, Italy

A total of 1419 children with type 1 diabetes mellitus was investigated in order to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT were identified, a number significantly higher (P0.0001) than the distribution reported in the normal paediatric population. No typical antibody pattern was seen prior to the onset of HT, nor was an antibody threshold level found which could have been diagnostic for this disease. Patients with subclinical hypothyroidism were treated with L-thyroxine and were investigated regarding the behaviour of anti-thyroid autoantibodies; however, no significant changes were seen. The data showed a high frequency of HT in diabetic children, and therefore we recommend that children with type 1 diabetes mellitus should be screened for thyroid autoantibodies and those positive should undergo periodic thyroid function testing.

Background The most striking event in the whole process of female puberty is the onset of menstruation. To our knowledge, no large population-based studies have been performed on the topic of menstrual health among Italian adolescents in recent years. The aims of this study were to produce up-to-date information on the menstrual pattern of Italian girls attending secondary school, and to estimate the prevalence of menstrual cycle abnormalities in this population. Methods This was a cross-sectional study on a population-based sample of Italian adolescents aged 13–21 years attending secondary school. Only girls who had already started menstruating were requested to participate. Information was collected by means of a questionnaire that included items on the girls’ demographic details, anthropometrics, smoking and drinking habits, use of contraceptive pills, and socioeconomic status. The questions on the girls’ menstrual pattern concerned their age at menarche, duration of the most recent menstruation intervals (35 days, variable), average days of bleeding (6 days), and any menstrual problems and their frequency. Results A total of 6,924 questionnaires were administered and 4,992 (71%) were returned. One hundred girls failed to report their date of birth, so 4,892 subjects were analyzed. The girls’ mean age was 17.1 years (SD ±1.4); their mean age at menarche was 12.4 (±1.3) years, median 12.4 years (95%CI 12.3–12.5). In our sample population, 3.0% (95%CI 2.5%-3.4%) of the girls had menstruation intervals of less than 21 days, while it was more than 35 days in 3.4% (95%CI 2.9%-3.9%). About 9% of the girls (95%CI 7.7%-9.4%) said the length of their menstruation interval was currently irregular. Short bleeding periods (6 days) in 19% (95%CI 17.9%-20.1%). Menstruation-related abdominal pain was reported by about 56% of our sample. About 6.2% of the girls (95%CI 5.4%-7.0%) were suffering from dysmenorrhea. Conclusions In conclusion, to the best of our knowledge, this is one of the largest studies on menstrual patterns and menstrual disorders among Italian adolescent girls. Adolescent girls referring persistent oligomenorrhoea, in first two years from menarche, had a higher risk for developing a persistent menstrual irregularity. They had longer bleeding periods (>6 days) and this has practical implications because it makes these adolescents potentially more susceptible to iron deficiency anemia. Clinicians need to identify menstrual abnormalities as early as possible in order to minimize their possible consequences and sequelae, and to promote proper health information. We recommend that adolescents should be encouraged to chart their menstrual frequency and regularity prospectively from the menarche onwards.

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)

In 1990, the Italian Study Group for Turner's Syndrome (ISGTS) undertook a nationwide survey, involving the retrospective collection of cross-sectional data and longitudinal growth profiles of 772 girls with Turner's syndrome born between 1950 and 1990. The study was carried out in 29 pediatric endocrinological centers. In this first report, the familial characteristics and neonatal data of Turner girls are described, compared to those of the general population, and related to postnatal somatic development. Furthermore, charts for birth weight and growth standards for height and weight from infancy to adulthood are presented (these are the first charts based on a large sample from the Mediterranean area). The main findings were: (1) incidence of Turner births increases with parental age or parity; (2) most of the neonates are small for dates; (3) girls with normal birth weight tend to be both taller and heavier than girls with low birth weight during the whole growth period; and (4) a 10-cm difference in midparental height leads to a 6.5-cm difference in adult stature.

To update the information on age at menarche in the Italian population and to verify the influence of genetic, nutritional, and socioeconomic factors on menarcheal age. Recent studies suggest that the magnitude of the secular trend toward an earlier age at menarche is slackening in industrialized countries.This multicenter study was conducted on a large, population-based sample of Italian high school girls (n = 3,783), using a self-administered questionnaire. The questionnaire was used to gather information on the girls, including demography, anthropometry, menarcheal date, regularity of menses, behavioral habits, and physical activity. The questionnaire was also used to gather information on parents, including demography and mothers' and sisters' menarcheal ages. The median age at menarche and its 95% confidence interval were estimated by means of Kaplan-Meier survival analysis. To identify the independent predictive factors of age at menarche, multivariate mixed-effects models were applied.The median age at menarche of the subjects was 12.4 years (95% confidence interval: 12.34-12.46). The girls had their first menses approximately one-quarter of a year (median-0.13) earlier than did their mothers (p.0001). Among all variables, parents' birth area, body mass index, family size, and the mother's menarcheal age were significantly and independently associated with age at menarche.This study confirmed the reduction in the trend toward earlier menarche in Italy. The results also confirmed that genetic and nutritional factors are strong markers for early menarche. Currently, socioeconomic factors do not seem to play as significant a role as in the past.

Bone development is a key process in the growing child. It is, therefore, of paramount importance to survey this process, which is characterized by increasing length and size of the bone together with its progressive mineralization. The bone status can be evaluated by different techniques, each of them having its pros and cons. Furthermore, it should be underlined that the results of bone assessment depend not only from the employed technique but also from the auxological characteristics of the subjects. It is, therefore, the aim of this review to examine the characteristics of the various methods of bone evaluation, such as dual energy X-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), ultrasound and metacarpal index and to explain how changes in bone structure and geometry may influence the results.

Altered frequency of the menstrual cycle accompanied by pain are manifestations of functional anomalies of the female reproductive system. These symptoms require prompt and accurate diagnosis and therapy to prevent a chronic condition that can seriously disturb the adolescent's psychic well being. The most common anomalies of the menstrual cycle and the causes of altered cycle frequency are outlined, as are useful criteria for diagnosing premenstrual syndrome dysmenorrhea and for distinguishing the causes and alterations in frequency and amount of menstrual discharge from other disturbances, including amenorrhea and abnormal uterine bleeding. The treatment of dysmenorrhea and quantitative alterations of the menstrual cycle is the focus of this article.

Context: Insulin-like factor 3 (INSL3) is produced by the Leydig cells, and in adults, its secretion is dependent on the state of differentiation of these cells, which, in turn, is dependent on LH. However, the secretion and regulation of INSL3 during puberty is unknown. Objective: Our objective was to evaluate INSL3 concentrations during normal male puberty and the relation of INSL3 to LH, FSH, and testosterone. Design and Setting: We conducted a cross-sectional study from January to December 2005 at academic clinics. Patients: Participating in the study were 75 healthy male subjects aged 9.5–17.5 yr, homogeneously distributed into five pubertal groups of 15 according to Tanner stages. Main Outcome Measures: We assessed mean testicular volume and LH, FSH, testosterone, and INSL3 concentrations in relation to age and pubertal stage. Results: We observed an increase of INSL3 and LH levels from Tanner stage 2 to 4, and an increase of FSH from stage 2 to 3. Testosterone levels increased from stage 3 to 4. No differences were seen for all measured hormones between stages 4 and 5. The increase in INSL3 seemed therefore to anticipate the increase in testosterone. However, INSL3 plasma concentrations at pubertal stages 4 and 5 are about one fourth of adult levels, whereas FSH, LH, and testosterone reached adult levels by stage 4. Positive significant correlations were found between INSL3 and LH for all pubertal stages. Conclusions: This study provides information on the physiological dynamics of INSL3, showing that the serum concentrations of this hormone increased progressively throughout puberty under the differentiating action of LH on Leydig cells. INSL3 is therefore confirmed to represent a marker of Leydig cell differentiation and function. However, a prolonged exposure to LH seems to be necessary to reach INSL3 concentrations of adults. A possible use of INSL3 in puberty disorders is promising.

The aim of this study was to investigate the ultrastructure of the interface zone between the nervous tissue and the connective vascular sheath that surround the central ganglia of the terrestrial snail of Megalobulimus abbreviatus and test its permeability using lanthanum as an electron dense tracer. To this purpose, ganglia from a group of snails were fixed by immersion in a 2% colloidal lanthanum solution, and a second group of animals was injected in the foot with either a 2%, 10% or 20% lanthanum nitrate solution and then sacrificed 2 or 24 h after injection. Ganglia from both groups were processed for transmission electron microscopy. The vascular endothelium, connective tissue and basal lamina of variable thickness that ensheathe the nervous tissue and glial cells of the nervous tissue constitute the interface zone between the haemolymph and the neurones. The injected lanthanum reached the connective tissue of the perineural capsule; however, it did not permeate into the nervous tissue because the basal lamina interposed between both tissues interrupted this passage. Moreover, the ganglia fixed with colloidal lanthanum showed electron dense precipitates between the glial processes in the area adjacent to the basal lamina. It can be concluded from these findings that, of the different components of the haemolymph-neuronal interface, only the basal lamina, between the perineural capsule and the nervous tissue, limits the traffic of substances to and from the central nervous system of this snail.

Summary objective In adults, excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed children. The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of GH-deficient children treated with GH for a period of 6 years. patients and design One hundred and twenty-eight children (40 females, 88 males) were included in the study. At the beginning of treatment chronological age was 8·9 ± 3·2 years, height standard deviation score (SDS) −2·43 ± 0·90 and body mass index (BMI) SDS 0·18 ± 1·60. At the end of the study chronological age was 13·0 ± 2·9 years, height SDS −1·24 ± 1·27 and BMI SDS 0·23 ± 1·54. GH was administered at a mean weekly dosage of 0·3 mg/kg, injected subcutaneously over 6–7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICKI). results No cases of impaired GT or diabetes were recorded during the follow-up period. IS, already lower than in controls before starting treatment with GH, decreased significantly during the first year of therapy (QUICKI: 0·346 ± 0·033 vs. 0·355 ± 0·044, P

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (1213.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.

Objectives:To evaluate the effectiveness of thyroid-stimulating hormone (TSH) and thyroxine [T4) measurements at neonatal screening for congenital hypothyroidism, we compared our false-negative results with those we would have obtained if we had used TSH screening alone.Subjects and methods:Between January 1989 and December 2001 745,258 newborns were screened (98.3% of total born) for congenital hypothyroidism in northeast Italy. T4 and TSH were measured simultaneously on blood spots collected after birth. Between 1989 and 1998, semiquantitative total T4 (tT4) and TSH concentrations were measured by radiolabelled immunological assay and, from 1999 to 2001, using time-resolved fluorometer Delfia instruments (EG&G Wallac Oy, Finland) and fluoroimmunometric assay (Delfia neonatal hTSH and T4 kits).Results:Ten neonates were missed by our screening programme (normal tT4 and TSH) and classified as false negatives; these infants were diagnosed later in life with central hypothyroidism. If we had measured TSH alone in our screening programme, we would have missed an additional 21 patients with low tT4 and normal TSH; of these, four were affected by central hypothyroidism and 17 were diagnosed within the second month of life as affected by primary hypothyroidism with delayed TSH rise.Conclusions:Simultaneous T4 and TSH measurements at neonatal screening can miss patients affected by central hypothyroidism. However, this screening procedure allows identification of cases of central hypothyroidism with low T4 values and those neonates affected by primary hypothyroidism with delayed TSH rise who we would have missed by using the TSH measure alone.

Aim: To evaluate the bone mineral density at lumbar spine and at femoral neck in a group of young adults in whom Graves’ disease developed during childhood and adolescence. Patients and Methods: We examined 28 patients (5 male, 23 female, age 20.9 ± 3.3 years) who were 11.8 ± 2.9 years old at the onset of Graves’ disease. They were treated either with methimazole (14 patients) or with methimazole plus l-thyroxine (14 patients). At the time of the investigation, 13 patients were considered cured following antithyroid treatment, 2 were still on antithyroid drugs, 3 were on replacement therapy with l-thyroxine because of hypothyroidism, and 10, treated either surgically or with 131I, were on replacement therapy. The bone mineral density was measured at the lumbar spine (L2–L4) and at the femoral neck, using dual-energy X-ray absorptiometry. Results: The spinal bone mineral density SD score was –0.28 ± 1.02, the femoral neck bone mineral density SD score was 0.36 ± 1.02, and both were not different from zero (NS). We did not find any correlation between the bone mineral density of the femoral neck and that of the lumbar spine and the clinical parameters. Conclusion: Graves’ disease, beginning in childhood and adolescence, when appropriately treated, does not affect attainment of peak bone mass.