Is There a Difference between Ultrasonographic (US) Uterine Changes of Oral Versus Transdermal (TD) 17ß Estradiol (17ß E2) in Girls with Turner Syndrome (TS)? Own Experience and Literature Review.

BACKGROUND: Among patients with Turner Syndrome (TS), premature ovarian failure is a main feature. Recently published consensus guidelines recommend that transdermal (TD) estradiol is the preferred route for estrogen replacement. Studies related to ultrasound (US) measurements during estrogen replacement in TS patients using estradiol (17ß E2) and correlating uterine growth with estrogen metabolites are limited. OBJECTIVES: To compare uterine morphology and hormonal changes depending on route of administration of 17ß E2 (oral vs. TD) in a small population of girls with TS. SUBJECTS: 11 hypogonadal girls with TS (mean (SE) age 14.5 ± 1.4 years; BMI -0.98 ± -1.0 SDS) who participated in a larger study on the effects of oral versus TD 17ß E2 agreed to do a sub-study on the effect of the form of 17ß E2 treatment on uterine size. METHODS: 17ß E2 was given orally or TD for 12 months, titrated to doses up to 2 mg orally or 100 µg TD to achieve normal estradiol levels. Subjects received monthly progesterone for 1 week for withdrawal bleeding. At baseline, 6 and 12 months, a pelvic ultrasound was performed while on estradiol only. RESULTS: Uterine morphology and endometrial thickness increased comparably in both groups. E2 concentrations were comparable at 12 months between both groups but E1 and E1S were lower in TD group at 12 months. CONCLUSIONS: According to our experience, in a group of TS patients randomized to oral vs TD 17ß E2 and monitored with trans-abdominal US, both groups achieved similar increases in uterine size comparable to normal women. To confirm our observation a larger sample and a longer evaluation period is needed.

Clinical and molecular characterization of Chilean patients with Léri-Weill dyschondrosteosis.

AIM: Léri-Weill dyschondrosteosis (LWD) is a mesomelic dysplasia with disproportionate short stature associated with short stature homeobox-containing gene (SHOX) haploinsufficiency. The objective of this study was to improve the diagnosis of patients with suspected LWD through molecular analysis. METHODS: Twelve patients from 11 families with a clinical diagnosis of LWD were analyzed with multiplex ligation-dependent probe amplification to detect deletions and duplications of SHOX and its enhancer regions. High resolution melting and sequencing was employed to screen for mutations in SHOX coding exons. RESULTS: The molecular-based screening strategy applied in these patients allowed detection of five SHOX deletions and two previously unreported SHOX missense mutations. CONCLUSION: Molecular studies confirmed the clinical diagnosis of LWD in seven out of 12 patients, which provided support for therapeutic decisions and improved genetic counseling in their families.

Syndrome-specific growth charts for 22q11.2 deletion syndrome in Caucasian children.

Growth faltering occurs frequently in infancy in the 22q11 Deletion syndrome (22q11 DS). The subsequent course of growth in childhood and outcome for final adult height lacks consensus. We analyzed 5,149 growth data points from 812 Caucasian subjects with 22q11 DS, from neonates to 37 years old. Charts were constructed for height, weight, body mass index, and head circumference (OFC) using the LMS Chart Maker program. These charts were compared with the WHO birth to 4 years growth standard and US CDC 2000 growth reference between 5 and 20 years. Starting from the 50th centile at birth, by 6-9 months of age boys mean height and weight had fallen to the 9th centile, as did girls height but their weight fell less markedly, to the 25th centile. Feeding difficulties were non-contributory. In children under 2 years old with congenital heart disease (CHD) mean weight was -0.5 SD lighter than no CHD. Catch up growth occurred, more rapid in weight than height in boys. Up to 10 years old both sexes tracked between the 9th and 25th centiles. In adolescence, the trend was to overweight rather than obesity. At 19 years mean height was -0.72 SD for boys, -0.89 SD girls. OFC was significantly smaller than the WHO standard in infancy, between the 9th and 25th centile, rising to the 25th centile by 5 years old. Thereafter the mean was close to the 9th centile of the OFC UK growth reference, more prolonged and marked than in previous studies.

A prospective cohort study of the prevalence of growth, facial, and central nervous system abnormalities in children with heavy prenatal alcohol exposure.

BACKGROUND: Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited. METHODS: This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed). Detailed alcohol consumption data were collected during the pregnancy. Children were evaluated up to 8.5 years of age by clinicians masked to exposure status. RESULTS: One or more functional central nervous system abnormalities were present in 44.0% (22/50) of the exposed children compared to 13.6% (6/44) of the unexposed (p = 0.002). Growth restriction was present in 27.2% (25/92) of the exposed and 12.5% (12/96) of the unexposed (p = 0.02). Abnormal facial features were present in 17.3% (14/81) of the exposed children compared to 1.1% (1/89) of the unexposed children (p = 0.0002) by direct examination. Of the 59 exposed children with data available to detect at least 1 abnormality, 12 (20.3%) had no abnormalities. Binge drinking from conception to recognition of pregnancy (OR = 1.48 per day, 95% CI: 1.15 to 1.91, p = 0.002) and after recognition of pregnancy (OR= 1.41 per day, 95% CI: 1.01 to 1.95, p = 0.04) and total number of drinks consumed per week from conception to recognition of pregnancy (OR = 1.02 per drink, 95% CI: 1.01 to 1.04, p = 0.0009) were significantly associated with abnormal child outcome. CONCLUSIONS: After exposure to heavy alcohol consumption during pregnancy, 80% of children had 1 or more abnormalities associated with alcohol exposure. Patterns of alcohol use that posed the greatest risk of adverse outcomes were binge drinking and high total weekly intake. Functional neurologic impairment occurred most frequently and may be the only sign to alert physicians to prenatal alcohol exposure.

[Viral respiratory co-infections in pediatric patients admitted for acute respiratory infection and their impact on clinical severity]. / Co-infección viral respiratoria en niños hospitalizados por infección respiratoria aguda y su impacto en la gravedad clínica.

INTRODUCTION: Respiratory viruses are the leading cause of acute respiratory tract infection (ARI) in children. It has been reported that viral respiratory co-infection could be associated with severe clinical course. OBJECTIVES: To describe the frequency of viral co-infection in children admitted for AlRI and evaluate whether this co-infection was associated with more severe clinical course. PATIENTS AND METHODS: Prospective, descriptive study in pediatric patients who were hospitalized for ARI, with molecular detection of at least 1 respiratory virus in nasopharyngeal sample studied by PCR-Microarray for 17 respiratory viruses. RESULTS: 110 out of 147 patients with detection of > 1 respiratory virus were included. Viral co-infection was detected in 41/110 (37%). 22/110 children (20%) were classified as moderate to severe clinical course and 88/110 (80%) were classified as mild clinical course. In the group of moderate to severe clinical course, viral respiratory co-infection was detected in 6/22 (27.3%), compared to 35/88 (39.8 %) in the mild clinical course group. No statistically significant difference was found regarding the presence of co-infection between groups (p = 0.33). CONCLUSIONS: We detected high rates of viral co-infection in children with ARI. It was not possible to demonstrate that viral co-infections were related with severe clinical course in hospitalized children.

Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results.

OBJECTIVE: Depot luteinizing-hormone releasing hormone (LHRH) agonist have been widely used for the treatment of central precocious puberty (CPP), but the optimal doses to obtain hormonal suppression are still unknown, especially in patients with higher weights. The goal of our study was to compare the efficacy of three leuprolide acetate (LA) preparations, suppressing gonadotropin secretion in patients with CPP. DESIGN: In an open 12-month protocol, we evaluated LA 7.5 mg/month, 11.25 and 22.5 every 3 months. PATIENTS: Fourteen girls with CPP and weights over 30 kg. MEASUREMENTS: Clinical, radiological and laboratory follow-up: GnRH test plus LH, FSH 40 min post analogue was performed periodically. RESULTS: Pretreatment basal and LHRH stimulated LH levels between groups were not different. Basal and LHRH stimulated LH levels decreased significantly between baseline and from 3 up to 12 months of therapy in all groups (P = 0.001). GnRH stimulated LH peak <2 IU/l, the main efficacy criterion was met in 80, 75 and 100% of the children at 6 months in the 7.5, 11.25, 22.5 mg doses respectively. By 12 months, 100% of patients had LH suppressed to <2 IU/l. CONCLUSIONS: These results affirm that 3-month injections may be a satisfactory alternative for the therapy of children with CPP to avoid monthly injections. In addition, suppression of LH occurs sooner in the 3-month 22.5 mg LA dose compared to the 3-month 11.5 mg; therefore, adequate dosing may be important for optimal outcome. Further investigation is needed in more patients over 30 kg, with longer treatment duration, and ultimately final height consideration.

Co-occurrence of Noonan and Cardiofaciocutaneous Syndrome Features in a Patient with KRAS Variant.

We report the case of a 3-year-old girl, who is the third child of nonconsanguineous parents, with short stature, hypertrophic cardiomyopathy, and mild dysmorphic features; all suggestive of Noonan syndrome. In addition, the patient presents with feeding difficulties, deep palmar and plantar creases, sparse hair, and delayed psychomotor and language development, all characteristics frequently observed in cardiofaciocutaneous syndrome. Molecular analysis of the Ras/ MAPK pathway genes using high-resolution melting curve analysis and gene sequencing revealed a de novo KRAS amino acid substitution of leucine to tryptophan at codon 53 (p.L53W). This substitution was recently described in an Iranian patient with Noonan syndrome. The findings described in this report expand the phenotypic heterogeneity observed in RASopathy patients harboring a KRAS substitution, and advocate for the inclusion of genes with low mutational frequency in genetic screening protocols for Noonan syndrome and other RASopathies.

Factors associated with post-menarcheal growth: results of a longitudinal study in Chilean girls from different socioeconomic statuses.

BACKGROUND: Menarche is the last stage of pubertal development, which coincides, with the completion of longitudinal growth. Our aim was to evaluate, post-menarcheal growth and clinical variables proposed to be associated with this growth. METHODS: In a prospective fashion, 106 healthy girls attending five different socioeconomic status (SES) schools of Santiago were randomly recruited. A pediatric endocrinologist obtained anthropometrics and registration of date at menarche every 6 months. The evolution of the girls' heights was assessed through mixed models adjusted to the SESes, parental height and body mass index (BMI). RESULTS: Sixty-three girls from a high socioeconomic status (HSS) and 50 from a low socioeconomic status (LSS) were followed. Four years post menarche, the girls reached a growth plateau and the average height gain was 5.2±2.5 cm. This gain was not associated with SES, BMI, nor with parental height (p=0.744). The only variable that modulated this gain was age at menarche (r=-0.1997, p=0.0332). There was an inverse correlation between height at the moment of menarche and the height reached after 4 years of follow-up adjusted to parental height (r=-0302, p=0.0011). CONCLUSIONS: Post-menarcheal growth ends 4 years post-event and is inversely correlated with the age at menarche and with the height at the moment of menarche independent of BMI, parental height and SES.

Ovarian function during puberty in girls with type 1 diabetes mellitus: response to leuprolide.

CONTEXT: An increased prevalence of polycystic ovary syndrome (PCOS) has been reported in adult women with type 1 diabetes mellitus (DM1). We investigated whether these hormonal abnormalities begin during puberty by evaluating the ovarian steroidogenic response to leuprolide acetate. METHODS: We studied 56 adolescent girls with DM1 (aged 12.3 +/- 0.2 yr) and 64 healthy girls (C) (aged 11.9 +/- 0.2 yr) up to 2 yr post menarche, matched by age, body mass index, and pubertal development. We evaluated anthropometrical data and Ferriman-Gallway score and performed a leuprolide test (500 microg sc) to study ovarian function. Ovarian volume was determined by transabdominal ultrasonography. RESULTS: We found five DM1 but no C girls with abnormally located terminal hair (Fisher's exact, P < 0.05). Free androgen index increased throughout puberty in girls with DM1 (ANOVA, P < 0.0001), which was associated with a decrease in SHBG levels in girls with DM1 (ANOVA, P < 0.0001). Stimulated 17OH progesterone (17OHProg) increased throughout puberty only in girls with DM1 (ANOVA, P < 0.01). Girls with DM1 at Tanner stage 5 had higher stimulated LH to FSH ratio, testosterone, and 17OHProg levels than girls at Tanner stage 4. In contrast, in C girls the stimulated testosterone, 17OHProg, and LH to FSH ratio were similar at Tanner stages 4 and 5. Ovarian volumes and uterine length were larger in girls with DM1 (analysis of covariance, P < 0.05). CONCLUSIONS: These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life.

Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome.

BACKGROUND: Noonan syndrome (NS) is an autosomal dominant syndrome characterized by typical dysmorphic features, cardiac anomalies as well as postnatal growth retardation, and is associated with Ras-MAPK pathway gene mutations. The purpose of this study was to improve the diagnosis of Chilean patients with suspected NS through molecular analysis. METHODS: We screened 18 Chilean patients with a clinical diagnosis of NS for mutations in PTPN11 by high resolution melting (HRM) and subsequent sequencing. RESULTS: Three PTPN11 missense mutations were detected in 22% of analyzed patients. Of these, two (c.181G>A and c.1510A>G) were previously reported and one was the novel substitution c.328G>A (p.E110K) affecting the linker stretch between the N-SH2 and C-SH2 domains of SHP-2 protein. CONCLUSION: Molecular studies confirmed the clinical diagnosis of NS in 4 of 18 patients, which provided support for therapeutic decisions and improved genetic counseling for their families.

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome.

BACKGROUND: It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients. METHODS: This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n = 93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n = 34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined. RESULTS: Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm. CONCLUSIONS: The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.

Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus.

OBJECTIVE: To evaluate the prevalence and risk factors of menstrual cycle irregularities in adolescents with type 1 diabetes mellitus. DESIGN: Prospective diary of menstrual cycle. SETTING: Pediatric diabetes clinics and nearby schools. PATIENT(S): Adolescents with type 1 diabetes mellitus treated with multiple daily insulin doses (n = 56) and 56 healthy adolescents. MAIN OUTCOME MEASURE(S): Duration and variability of menstrual cycle. RESULT(S): Duration of the menstrual cycle was 48 ± 39 and 32 ± 7 days in girls with type 1 diabetes mellitus and controls, respectively. Oligomenorrhea (58.9% vs. 19.6%) and amenorrhea (10.7% vs. 1.8%) were more prevalent in girls with type 1 diabetes mellitus than in controls. Oligomenorrhea was observed in 53.3% of the girls with type 1 diabetes mellitus with optimal metabolic control. Girls with an HbA1c level of 7.6% to 8.9% exhibited increased cycle duration, menstrual cycle variability, and prevalence of oligomenorrhea compared with controls. Regression analysis showed that, for each point of increase in HbA1c, the menstrual cycle duration increased by 5.1 days. Cycle variability was associated with a higher daily insulin dose. CONCLUSION(S): Despite optimal metabolic control, a higher prevalence of oligomenorrhea was observed in girls with type 1 diabetes mellitus compared with controls. This is the first report to describe the high variability of the menstrual cycle in type 1 diabetes mellitus. HbA1c and insulin dose are important factors related to menstrual irregularities in type 1 diabetes mellitus.

[Congenital hypopituitarism: report of 23 cases]. / Hipopituitarismo congénito: Experiencia en 23 casos.

BACKGROUND: Congenital hypopituitarism is an uncommon cause of hypophyseal insufficiency It is less common than growth hormone deficiency which has an incidence of 1:4.000 to 1:8.000 live newborns. Early diagnosis of this condition is important to prevent impairment of cognitive function, poor growth and alterations in metabolic profile in these patients. AIM: To report 23 patients diagnosed with congenital hypopituitarism. MATERIAL AND METHODS: Retrospective review of clinical records of 23 patients (12 males) with congenital hypopituitarism, diagnosed during a 21 years period. In a group of 16 patients a molecular study was performed searching for mutations in HESX1, PROP-1 or POUF-1. RESULTS: Short stature was the most frequent sign at the first evaluation, followed by neonatal hypoglycemia and presence of nystagmus, strabismus, atrophic optic nerve or malformations in the middle line showed in CNS imaging, suggesting septo-optic-dysplasia. All male patients diagnosed during neonatal period, exhibited micropenis. CNS images showed isolated hypophyseal hypoplasia or associated to an ectopic neurohypophysis in most patients. No patient in the subgroup subjected to molecular analysis had any of the mutations in the searched genes. CONCLUSIONS: The diagnosis of hypopituitarism must be based on clinical grounds, especially when hypoglycemia, prolonged jaundice, micropenis or midline alterations are found in the neonatal period.

[Age of menarche and its relationship with body mass index and socioeconomic status]. / Edad de la menarquia y su relación con el nivel socioeconómico e índice de masa corporal.

BACKGROUND: A decline in the age of menarche was observed from early 1900s to the 1970s. However, it is not known if a further decline occurred thereafter. AIM: To evaluate the age of menarche in girls from Santiago, Chile and its relationship with body mass index (BMI) and socioeconomic status. MATERIAL AND METHODS: We studied 1302 healthy girls aged 7 to 19 years. Age of menarche was evaluated through a questionnaire to the patient and her parents. Kaplan-Meier curves were used to determine age of menarche and Cox regression analysis was employed to evaluate the effect of the type of school and BMI on the age of menarche. RESULTS: The mean age at menarche was 12.7+/-0.04 years. Girls from public and private schools had their period at 12.5+/-0.1 and 13.05+/-0.05 years respectively. A negative correlation between z scores for BMI and age of menarche was observed (r-0.3: p =0.001). Girls whose menarche occurred before 11.5 years had higher z scores for BMI and a larger proportion were overweight, compared to girls who had menarche later. Cox regression analysis showed that after adjustment for BMI, age of menarche was similar in both types of schools. CONCLUSIONS: Age of menarche is occurring three months earlier in girls from public schools, which is associated with higher z scores for BMI. Type of school, a marker of socio-economic status in Chile, affects timing of menarche due to differences in body mass index.

Adrenarche in Prader-Willi syndrome appears not related to insulin sensitivity and serum adiponectin.

Prader-Willi syndrome (PWS) is a genetic disorder characterized by dysmorphic features, obesity, hypogonadism, hypotonia and mental retardation. Obesity has been linked to insulin resistance and the latter has also been associated with premature adrenarche. Since up to date a controlled study to investigate adrenarche and its hormonal regulation was lacking in PWS, our aim was to assess whether prepubertal PWS patients develop premature adrenarche and its relationship with markers of insulin sensitivity. Fourteen prepubertal children with PWS (6 M, 8 F) and 10 non-syndromal simple obese matched controls (5 M, 5 F) participated (mean age: 7.62 +/- 1.84 years). A fasting blood sample was obtained for adrenal and ovarian androgens, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1, leptin, adiponectin and a lipid profile. Thereafter an oral glucose tolerance test was performed. PWS patients were smaller at birth and a higher proportion displayed premature pubarche. No differences were found in testosterone, androstenedione, sex hormone binding globulin, free androgen index, homeostatic model assessment-IR, 2-hour insulin, leptin or adiponectin levels. 17-hydroxyprogesterone and DHEAS levels however, were significantly higher in PWS. IGF-I levels were significantly lower in PWS and correlated significantly with height SDS (p < 0.05). In conclusion, a higher proportion of premature adrenarche in our PW patients was observed, which was not explained by differences in insulin sensitivity or plasma levels of adipokines and IGF-I.

Co-infección viral respiratoria en niños hospitalizados por infección respiratoria aguda y su impacto en la gravedad clínica / Viral respiratory co-infections in pediatric patients admitted for acute respiratory infection and their impact on clinical severity

Introduction: Respiratory viruses are the leading cause of acute respiratory tract infection (ARI) in children. It has been reported that viral respiratory co-infection could be associated with severe clinical course. Objectives: To describe the frequency of viral co-infection in children admitted for AlRI and evaluate whether this co-infection was associated with more severe clinical course. Patients and Methods: Prospective, descriptive study in pediatric patients who were hospitalized for ARI, with molecular detection of at least 1 respiratory virus in nasopharyngeal sample studied by PCR-Microarray for 17 respiratory viruses. Results: 110 out of 147 patients with detection of > 1 respiratory virus were included. Viral co-infection was detected in 41/110 (37%). 22/110 children (20%) were classified as moderate to severe clinical course and 88/110 (80%) were classified as mild clinical course. In the group of moderate to severe clinical course, viral respiratory co-infection was detected in 6/22 (27.3%), compared to 35/88 (39.8 %) in the mild clinical course group. No statistically significant difference was found regarding the presence of co-infection between groups (p = 0.33). Conclusions: We detected high rates of viral co-infection in children with ARI. It was not possible to demonstrate that viral co-infections were related with severe clinical course in hospitalized children.

Introducción: Los virus respiratorios son la principal causa de infección aguda del tracto respiratorio (IRA) en pediatría. Se ha descrito que la co-infección viral podría relacionarse con infecciones virales respiratorias de curso más grave. Objetivo: Describir la frecuencia de co-infección viral en niños hospitalizados por IRA y determinar si esta co-infección se relacionó con una evolución clínica más grave. Pacientes y Métodos: Estudio descriptivo, prospectivo, en pacientes pediátricos hospitalizados por IRA entre junio y agosto 2010, que tuvieron detección molecular de al menos un virus respiratorio en muestra nasofaríngea estudiada por RPC-microarreglo para 17 virus respiratorios. Resultados: Se incluyeron 110 de 147 pacientes con detección de > 1 virus respiratorio. Se detectó co-infección viral en 41/110 (37%). En cuanto a evolución clínica, 22/110 niños (20%) se clasificaron como evolución moderada a grave (MG) y 88/110 (80%) se clasificaron como evolución leve (L). En el grupo MG se detectó co-infección viral respiratoria en 6/22 (27,3%), mientras que en el grupo L se detectó co-infección en 35/88 (39,8%). No se encontró diferencia significativa en relación a la presencia de co-infección entre ambos grupos (p = 0,33). Conclusión: Se demostró la presencia de co-infección viral en un alto porcentaje de niños con IRA. No fue posible demostrar que la presencia de coinfección viral tenga relación con una evolución clínica más grave en estos niños hospitalizados.

[Age of pubertal events in Chilean school age girls and its relationship with socioeconomic status and body mass index]. / Cronología del desarrollo puberal en niñas escolares de Santiago: relación con nivel socio-económico e índice de masa corporal.

BACKGROUND: Recent studies in the United States have demonstrated that a significant proportion of girls show thelarche before the age of eight years. Nutritional status, geographic influences and racial factors are known to affect the timing of puberty. AIM: To evaluate the age of onset of puberty, development of secondary sexual characteristics and menarche in Chilean girls, and its relation to obesity and socioeconomic status. MATERIAL AND METHODS: Healthy girls attending elementary school, from first to ninth grade in Santiago, Chile, were studied. A pediatric endocrinologist evaluated pubertal development using Tanner classification. Breast development was assessed by inspection and breast palpation. Average age of onset of pubertal events was determined by probit analysis. RESULTS: A total of 758 girls, aged 5.8 to 16.1 years, were recruited. Obesity, defined as a BMI greater than 90th percentile, was found in 24.4%. The age of menarche was 12.7 years, the onset of Tanner stage 2 breast development and pubic hair was at 8.9 and 10.4 years, respectively. Sixteen percent of girls aged 7 to 7.9 years, had thelarche. Upper class girls showed a later onset of breast Tanner stage 4 stage than low-middle class girls. Obesity was not found in logistic regression analysis to be a significant predictive factor in the onset of puberty. CONCLUSIONS: The age of menarche has not changed in the last thirty years, but an earlier onset of thelarche has occurred. The high frequency of thelarche between 7 and 8 years suggests that the normal age of breast development should be revised.

Ponderal gain, waist-to-hip ratio, and pubertal development in girls with type-1 diabetes mellitus.

OBJECTIVES: We assessed pubertal development, height, weight, and waist-to-hip ratio (WHR), an index of central adiposity during puberty, in girls with type-1 diabetes mellitus (T1DM), compared to a contemporary control group. METHODS: Pubertal development, weight, height and WHR were studied in 100 pubertal girls with T1DM, and were compared to a control group of 576 normal girls (C), recruited from schools with a similar socioeconomic level and ethnicity. The age of onset of various pubertal stages was estimated by using probit analysis. RESULTS: Breast Tanner stage 2 (BT2) began at 8.89 +/- 0.11 and 9.10 +/- 0.28 yr in C and T1DM, respectively. A delay of 6 months was observed in T1DM for BT3 and BT4 (p < 0.05). Menarche occurred 6 months later in girls with T1DM (p = 0.03). WHR decreased during puberty in C (p < 0.001), but not in T1DM. In girls with T1DM, the body mass index standard deviation score (BMI-SDS) increased throughout puberty (p < 0.001), but it was stable in C. In T1DM girls, BMI-SDS, but not hemoglobin A1c levels (HbA1c), was a significant determinant of pubertal development. Final height was similar in T1DM and C. CONCLUSIONS: Pubertal development in girls with T1DM occurred earlier than described in historical cohorts, but a later onset of menarche and final stages of breast development were observed. The increase in BMI-SDS and the stability of WHR in girls with T1DM during puberty suggest that this period may be critical for determining later weight gain and body composition in adult women with this condition.

Diabetes mellitus neonatal transitoria por duplicación paterna 6q24 / Transient neonatal mellitus diabetes due to paternal duplication 6q24

Neonatal diabetes mellitus is defined as severe hyperglycemia beginning during the first six months of life, lasting at least one month and needing insulin as a treatment. The incidence is about 1 in 200.000 born alive. We report a preterm female newborn, small for gestational age, whose actual age is 19 months. At the third day of life she became severely ill, with serious shock, losing 20 percent of her weight at birth. Laboratory work-up showed a blood glucose level of 633 mg/dl, hypernatremia, metabolic acidosis and renal failure. During the initial 4 months she was treated with insulin infusions that were tapered and finally discontinued at four months of age. The molecular study of this patient showed abnormal maternal methylation at chromosome 6 and the novo paternal duplication of 6q24.

Hipopituitarismo congénito: experiencia en 23 casos / Congenital hypopituitarism: report of 23 cases

Background: Congenital hypopituitarism is an uncommon cause of hypophyseal insufficiency It is less common than growth hormone deficiency which has an incidence of 1:4.000 to 1:8.000 Uve newborns. Early diagnosis ofthis condition is important to prevent impairment of cognitive function, poor growth and alterations in metabolic profile in these patients. Aim: To report 23 patients diagnosed with congenital hypopituitarism. Material and methods: Retrospective review of clinical records of 23 patients (12 males) with congenital hypopituitarism, diagnosed during a 21 years period. In a group of 16 patients a molecular study was performed searching for mutations in HESX1, PROP-1 or POUF-1. Results: Short stature was the most frequent sign at the first evaluation, followed by neonatal hypoglycemia and presence of nistagmus, strabismus, atrophic optic nerve or malformations in the middle Une showed in CNS imaging, suggesting septo-optic-dysplasia. All male patients diagnosed during neonatal period, exhibited micropenis. CNS images showed isolated hypophyseal hypoplasia or associated to an ectopic neurohypophysis in most patients. No patient in the subgroup subjected to molecular analysis had any of the mutations in the searched genes. Conclusions: The diagnosis of hypopituitarism must be based on clinical grounds, speciaUy when hypoglycemia, prolonged jaundice, micropenis or midline alterations are found in the neonatal period.