Nancy Unanue

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

Abstract:  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.

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.

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.

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.

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.

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.

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

BackgroundIt 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.MethodsThis 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.ResultsSeventy 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.ConclusionsThe 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.

Hipopituitarismo congénito: Experiencia en 23 casos

Congenital hypopituitarism is an uncommon causeof hypophyseal insufficiency. It is less common than growth hormone deficiency, which has anincidence of 1:4.000 to 1:8.000 live newborns. Early diagnosis of this condition is important toprevent impairment of cognitive function, poor growth and alterations in metabolic profile inthese patients.

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

Abstract 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.

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

Abstract 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.