Size of the exon 1-CAG repeats of the androgen receptor gene employed as a molecular marker in the diagnosis of Turner syndrome in girls with short stature

Turner syndrome (TS) is one of the most common chromosomal abnormalities among girls. Complete monosomy of X chromosome is responsible for almost 50% of all cases of TS, and mosaicism and X anomaly are detected in the other half. It has already been demonstrated that early diagnosis of these children allows appropriate growth hormone treatment with better final height prognosis and introduction of estrogen at an ideal chronological age. Sixty-four short-stature girls were selected and the clinical data obtained were birth weight and height, weight and height at the first medical visit and target height. Other clinical data including cardiac and renal abnormalities, otitis, Hashimoto thyroiditis, cubitus valgus, short neck, widely separated nipples, and pigmented nevi were obtained from the patients' medical records. The aim of the present study was to evaluate the screening of a group of short-stature girls for TS based on the number of CAG repeats of the androgen receptor gene analyzed by GeneScan software. Patient samples with two alleles (heterozygous) were 49/64 (76.5%) and with one allele (homozygous) were 15/64 (23.5%). A karyotype was determined in 30 patients, 9 homozygous and 21 heterozygous. In the homozygous group, 6/9 were 45,X and 3/9 were 46,XX. In the heterozygous group, 17/21 were 46,XX, and 4/21 were TS patients with mosaicism (45,X/46,XX; 45,X/46XiXq; 46XdelXp). The pattern obtained by GeneScan in two patients with mosaicism in the karyotype was an imbalance between the peak heights of the two alleles, suggesting that this imbalance could be present when there is a mosaicism. The frequency of TS abnormalities (18.7%) did not differ between TS and 46,XX girls. Thus, it is important to accurately assess the incidence of TS in growth-retarded girls, even in the absence of other dysmorphisms. In this study, we diagnosed 6 cases of TS 45,X (9.4%) by molecular analysis, with a 100% sensitivity and 85% specificity. This molecular analysis was able to detect all cases of TS 45,X and the majority of mosaicisms, without the need for more X chromosome markers. In conclusion, determining the number of CAG repeats of the androgen receptor gene analyzed by GeneScan was a fast method with high sensitivity for the detection of TS 45,X, suggesting that it could be interesting as a method for screening a population of growth-retarded girls.     

Early anthropometric indices predict short stature and overweight status in a cohort of Peruvians in early adolescence

While childhood malnutrition is associated with increased morbidity and mortality, less well understood is how early childhood growth influences height and body composition later in life. We revisited 152 Peruvian children who participated in a birth cohort study between 1995 and 1998, and obtained anthropometric and bioimpedance measurements 11-14 years later. We used multivariable regression models to study the effects of childhood anthropometric indices on height and body composition in early adolescence. Each standard deviation decrease in length-for-age at birth was associated with a decrease in adolescent height-for-age of 0.7 SD in both boys and girls (all P < 0.001) and 9.7 greater odds of stunting (95% CI 3.3-28.6). Each SD decrease in length-for-age in the first 30 months of life was associated with a decrease in adolescent height-for-age of 0.4 in boys and 0.6 standard deviation in girls (all P < 0.001) and with 5.8 greater odds of stunting (95% CI 2.6-13.5). The effect of weight gain during early childhood on weight in early adolescence was more complex to understand. Weight-for-length at birth and rate of change in weight-for-length in early childhood were positively associated with age- and sex-adjusted body mass index and a greater risk of being overweight in early adolescence. Linear growth retardation in early childhood is a strong determinant of adolescent stature, indicating that, in developing countries, growth failure in height during early childhood persists through early adolescence. Interventions addressing linear growth retardation in childhood are likely to improve adolescent stature and related-health outcomes in adulthood.     

Turner syndrome, insulin sensitivity and growth hormone treatment

Mild insulin resistance appears to be an early metabolic defect in girls with Turner syndrome (TS). Impaired glucose tolerance has been reported in 10-34% of patients with TS, and type 2 diabetes mellitus is 2-4 times more common and occurs at a younger age in girls with TS than in the general population. In a mixed longitudinal and cross-sectional study, we analysed carbohydrate tolerance and insulin sensitivity in 46 children and adolescents with TS who reached their final height after long-term treatment (mean 6.3 +/- 2.5 years) with growth hormone (GH: 0.33 mg/kg/week [0.05 mg/kg/day]), and in 36 of these patients who were followed-up after the cessation of GH therapy (mean follow-up, 2.6 +/- 2.5 years; range, 1-9.5 years). Patients with TS were compared with an age-matched female control group. Insulin sensitivity appeared to be lower in patients with TS than in controls, even before the start of GH therapy. As in controls, insulin sensitivity decreased with age in patients with TS, and levels were lower in those aged >12 years than in those aged <12 years. GH therapy resulted in good catch-up growth in patients with TS, with final height significantly higher than projected height evaluated before the initiation of GH therapy. Insulin sensitivity increased after 7-8 years of therapy and, on the cessation of GH therapy, returned to pre-treatment levels. The increase in insulin sensitivity seen on the cessation of GH therapy appeared to be influenced negatively by body mass index and triglyceride levels, and correlated positively with the number of years since cessation of GH therapy. As in the general population, excess weight and an abnormal lipid profile, in particular excess triglyceride levels, worsened insulin sensitivity. In conclusion, our study confirms that GH therapy reduces insulin sensitivity, but at its cessation there is a return to pre-therapy values. We therefore report a progressive improvement in carbohydrate tolerance and insulin function in patients with TS, despite an increase in age.     

Psychosocial functioning after discontinuation of long-term growth hormone treatment in girls with Turner syndrome

It is common practice in the case of Turner syndrome (TS) to treat short stature with GH treatment and to induce puberty with estrogens at an age as close to normal puberty as possible. This approach in most cases leads to a height in the normal range in childhood, adolescence, and adulthood in TS. Little data is available, however, on its effect on psychosocial functioning. In the present study, we evaluated psychosocial functioning in a group of 50 women with TS, after reaching final height in two multicenter GH trials. Thirty-six girls participated in a randomized dose-response study from mean (SEM) age 6.8 (0.4) years, and 14 girls participated in a frequency-response study from age 13.2 (0.4) years. After discontinuation of long-term GH treatment, these 50 girls were evaluated for psychosocial functioning at a mean age of 18.8 (0.3) years. GH was given in a dosage of 4 IU/m2/day (approximately 0.045 mg/kg/day), 6 IU/m2/day, or 8 IU/m2/day. After a mean GH treatment duration of 7.1 (0.4) years, mean final height (ref. normal girls) was FH1.2 (0.2) SD score. Behavioral problem scores (Achenbach) of the TS women were comparable to normal Dutch peers. Although self-perception (Harter total scale: p < 0.01), and bodily attitude (Baardman: p < 0.05) was significantly less positive than for their normal Dutch peers, we found no evidence of depression. TS women rated their family functioning higher than their Dutch peers (p < 0.0001), and had a slightly different coping pattern. These results show that even after reaching a height in most cases within the normal range and puberty induction at a pubertal age, some women with TS still experience psychosocial problems. It is likely, however, that GH and estrogen treatment improved psychosocial functioning. Long-term follow-up of these GH-treated patients will allow an evaluation of their life achievements.     

Gonadotropin secretion in girls with turner syndrome measured by an ultrasensitive immunochemiluminometric assay

BACKGROUND/AIM: Gonadotropin levels measured by radioimmunoassays are high in girls with Turner syndrome (TS), but overlap significantly with those of normal girls. We hypothesized that gonadotropin levels would be above the normal range in TS when measured by ultrasensitive assays. METHODS: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured in 68 TS, and 133 control girls using ultrasensitive immunochemiluminometric assays (ICMA). RESULTS: FSH levels in TS and normal girls were highest in early childhood (56.0 +/- 39.7 and 2.3 +/- 1.8 IU/l, respectively), declined at 6-10 years of age (11.3 +/- 13.1 and 1.8 +/- 0.9 IU/l, respectively), and then increased again (104.4 +/- 68.9 and 4.9 +/- 2.4 IU/l, respectively). FSH was in the normal range on 11 of 27 occasions in TS girls with ages 5-10 years, and on 3 of 44 occasions in >10 years. Although average LH values were higher than those of controls, they often overlapped the normal range. CONCLUSION: A significant number of TS girls have normal gonadotropins by ICMA. Spontaneous gonadotropin levels are not an adequate screening test for the diagnosis of TS but may prove useful for predicting the gonadal function and determining the appropriate timing of estrogen replacement therapy.     

Effects of growth hormone on cognitive function

Whether growth hormone deficiency (GHD) and/or treatment in childhood and adolescence influences cognitive outcome in children with GHD or girls with Turner syndrome (TS) is controversial. Previous studies also suggest that quality of life (QoL) is reduced in adults with GHD, particularly in the areas of social isolation and fatigue. Baseline QoL scores were significantly lower in patients with GHD than in the general population of the same age, gender, and nationality. Unfortunately, few data are available describing QoL in children with GHD. TS is a genetic disorder characterized by short stature, gonadal dysgenesis, and a particular neurocognitive profile of normally developed language abilities (particularly verbal intelligence quotients) and impaired visual-spatial and/or visual-perceptual abilities. This study evaluated the effects of GH treatment on neurocognitive function in girls with TS who were enrolled in a long-term, double-blind, placebo-controlled trial of the effects of GH treatment on final adult height. Treatment duration ranged from 1 to 7 years. The major result of this study was the absence of GH treatment effects on cognitive function in girls with TS. GHD and/or treatment in childhood and adulthood influences cognitive and/or QoL outcomes in some but not all studies. This study did not support a role for GH in influencing the characteristic nonverbal neurocognitive deficits associated with TS. However, evaluation of QoL should be a part of the routine clinical management of patients with GHD or TS.     

Oestrogen deficiency and growth hormone treatment in childhood are not associated with hearing in adults with turner syndrome

BACKGROUND/AIMS: Women with Turner syndrome (TS) have an increased prevalence of hearing loss, with conductive (CHL) and sensorineural (SNHL) components. The association between hearing loss and clinical parameters, particularly oestrogen and previous growth hormone (GH) treatment, was investigated. METHODS: A cross-sectional study of pure tone audiometry tests in an adult TS population. Previous ENT history, karyotype, anthropomorphic measurements and the impact of oestrogen and childhood GH therapy were assessed. One hundred and thirty-eight women (median age 29, range 16-67 years) completed the study. RESULTS: Normal hearing was found in 20.3% of women, CHL in 18.8%, SNHL in 57.2% and confounding factors in 3.6%. Neither CHL nor SNHL were associated with oestrogen deficiency or GH treatment independent of age. CHL but not SNHL was more common in those with a history of recurrent otitis media (p < 0.01) and monosomy 45,X (p < 0.01). CONCLUSIONS: Current regimens of oestrogen and GH therapy have no impact on adult hearing loss in TS, independent of age. The prevalence of SNHL increases with age. CHL but not SNHL is associated with ENT history and karyotype. According to present evidence, the only possible intervention to reduce hearing loss in women with TS remains assiduous treatment of ENT problems in childhood.     

Differences in infantile growth patterns in Turner syndrome girls with and without spontaneous puberty.

OBJECTIVE: The role of prepubertal estrogen in child growth was modeled using Turner's syndrome, comparing growth patterns of girls who later did or did not enter puberty spontaneously. The hypothesis was that TS patients with normal prepubertal estrogen levels would have a different growth pattern from those with subnormal estrogen levels. STUDY DESIGN: Growth data from 78 full-term patients with Turner's syndrome were collected retrospectively. 24/78 later developed spontaneous puberty, (+Pub), and their growth data were compared to TS patients without spontaneous puberty (-Pub). A nonlinear mixed model was fitted using the bi-exponential model. RESULTS: The growth velocity difference between the -Pub and +Pub groups suggests an early infantile growth advantage in the -Pub group, which disappears before the end of the first year of life; growth velocity remains similar (+/- 1 cm/y) for the next 6 years and declines at age 7-8 years in the +Pub group faster than it does in the -Pub group. Bi-exponential analysis showed that both the 1st (restrictive) and 2nd exponent (forward) were different (p = 0.0003). CONCLUSIONS: Comparison of girls with or without spontaneous puberty suggests a role for estrogen in child growth. Estrogens restrict infantile growth, as well as growth during the mid-childhood spurt.     

Psychosocial functioning, self-perception and body image and their auxologic correlates in growth hormone and oestrogen-treated young adult women with Turner syndrome

BACKGROUND: Few data are available on the psychosocial status of growth hormone (GH) and oestrogen treated women with Turner syndrome (TS). In this study, we evaluated psychosocial functioning, self-concept and body image in GH and oestrogen treated young adult women with TS and we studied the relationship with auxological parameters. PATIENTS AND METHODS: Thirty women with TS (mean +/- SD age: 22.1 +/- 2.4 years), all treated with GH and oestrogens if indicated, and an age-matched reference group of 44 non-Turner female students (age: 20.5 +/- 2.1 years) completed 3 questionnaires evaluating, respectively, behavioural and emotional problems (Young Adult Self Report), self-concept (Self Perception Profile for College Students) and body-image (Body Attitude Scale). RESULTS: TS patients did not report more behavioural and emotional problems compared to the non-TS females except for attention problems; they even reported fewer problems on some subscales (somatic complaints, thought problems, delinquent behaviour). TS patients did not differ from the non-TS female group in their bodily satisfaction. TS patients, particularly patients with a 45,X karyotype, perceived themselves as less socially competent. BMI was significantly related to the appraisal score of the Body Attitude Scale, whereas height was not related to any of the evaluated psychosocial parameters. CONCLUSION: The psychosocial adaptation of young adult women with TS, diagnosed at an early age and treated during childhood with GH and oestrogens if indicated, appears to be quite satisfactory. Follow-up of adult TS patients should not neglect the problem of overweight and associated psychosocial consequences.     

The childhood component of the ICP model is appropriate for growth analysis of short Israeli children

OBJECTIVE: To determine whether the childhood component of the infancy-childhood-puberty (ICP) model is appropriate for growth analysis of short Israeli children. SUBJECTS AND METHODS: From 204 short, prepubertal children, 2-16 years of age, 1,516 height measurements were analyzed. For each child's measurements, a best-fitted line based on C equation of ICP has been drawn and the distribution of measurement points around that line was calculated. RESULTS: Ninety percent of the measurements were at a distance of no more than +/- 2 cm from the best-fitted ICP line. CONCLUSION: The C component of ICP model can be used as a growth analysis tool for shorter than average, prepubertal, Israeli children, older than 2 years of age.     

Growth and somatotype patterns of manus children,territory of Papua and New Guinea: Application of a modified somatotype method to the study of growth patterns

The growth and somatotype patterns of Manus children, Territory of Papua and New Guinea, reflected in anthropometric measurements and somatotype photographs, is reported for 438 children, ranging from 15 months of age to maturity. Somatotype distributions and individual somatotype photographs indicate little difference between boys and girls from age 1 to 4 years; between age 5 and 9 years boys shift toward higher second component ratings; between age 10 and 18 years boys shift toward higher second and third component ratings, while girls shift toward higher first and third component ratings. Four sample somatotype photographs are representative of the population at age 10 and 14 years, and show age and sex characters easily noted visually. Comparison of height, weight and subscapula skinfold values show that the Manus children resemble the Kaiapit and Bundi children of the New Guinea highlands populations reported by Malcolm in the form of their growth curves but not in growth rates. Manus children grow more slowly than the British, but faster than the Kaiapit and Bundi children. While low skinfold values and height/weight ratios derived from means for height and weight suggest somatotypic similarity of the Manus, Kaiapit and Bundi populations, somatotype photographs are needed for confirmation. Lacking historical information and genetic evidence, we can speculare that diet, nutrition, climate and perhaps physical activity are factors which influence the growth patterns of these populations. The protein intake derived from fish and other seafood may be an important factor in the relatively fast growth and earlier maturation of the Manus. Malcolm thinks that low protein intake plays an important role with the Kaiapit and Bundi, but does not rule out survival value of slow growth and short stature.     

Maxillary volume growth in childhood

Nasomaxillary abnormalities in form, position, and development in children are often prominent features of craniosynostosis, and in particular, craniofacial dysostosis. While attempting to quantitatively assess the volumetric maxillary deficiency in these patients, it became apparent that there was no "normal" reference range for maxillary volumes throughout childhood that could be used for comparison. The aim of this study was to generate a model for measuring maxillary volume and subsequent changes throughout childhood. The technique of segmentation was applied to magnetic resonance images obtained in 55 healthy children (30 boys, 25 girls), aged 1 month to 184 months (15.33 years). Maxillary volumes were plotted against age for boys and girls to create a model for normal maxillary growth during the first 15 years of life. Maxillary volumes were larger in boys at all ages. However, the pattern of maxillary growth in boys and girls was similar and could be divided into three periods, each lasting approximately 5 years. During the first 5 years of life, there is a steady increase in maxillary volume, at the end of which the maxilla has reached 53 percent of the volume recorded at 15 years. There is an accelerated rate of growth between 5 and 11 years, which corresponds to the development and eruption of the permanent dentition. Thereafter, until the age of 15 years, the rate of growth of the maxilla plateaus. Maxillary volume in the first 12 months of life is, on average, 29 cm3 in boys and 25 cm3 in girls. By 15 years of age, it has increased to an average of 73.0 cm3 in boys and 59.4 cm3 in girls (an increase by a factor of 2.5 in boys and 2.4 in girls). The difference between the two sexes is statistically significant for the entire series (boys: mean maxillary volume = 56.55 cm3, SD = 24.61; girls: mean maxillary volume = 40.68, SD = 17.69, p = 0.009, one-way analysis of variance).     

Cross-sectional growth study in patients with Turner's syndrome

The body height, weight and growth velocity were investigated in 416 patients with Turner's syndrome whose age ranged from 3 to 17 years. They were all prepubertal at the time of the present study. The chromosomal analysis revealed 45, X monosomy in 148 cases, mosaicism in 208 cases, and nonmosaic structural abnormalities of X chromosome in 60 cases. There were no significant differences in height, growth velocity and weight between the patients with the 45, X karyotype and those with other chromosomal variants at any age. Combined mean heights at 3, 10 and 17 years of age were 86.0 +/- 3.5 (m +/- SD), 116.7 +/- 5.8 and 136.8 +/- 4.8 cm, respectively. These values were below -2.0 SD of normal Japanese girls. The growth velocity was 6.0 +/- 0.5 cm/year at 4 years of age, but decreased gradually and was 1.6 +/- 0.7 cm/year at 17 years of age. The degree of overweight was within +/- 10% of ideal body weight for height between the ages of 3 and 8, 10-20% between the ages of 9 and 10, and 20-30% above the age of 11 years.     

Body composition in Egyptian Turner syndrome girls

OBJECTIVE:

This cross-sectional study was undertaken to construct the new body fat % curve and provide body composition reference data for adolescent girls with Turner syndrome (TS). They diagnosed cytogenetically by blood karyotyping and not treated with growth hormone (GH).

MATERIALS AND METHODS:

The study included 70 TS girls from age 13 years to age 17 years. Body composition was measured by bioelectrical impedance. Smoothed centile charts were derived by using the least mean square (LMS) method.

RESULTS:

The new body fat curves reflect the increase of body fat mass (FM) from age 13 years to age 17 years. Body FM % of Egyptian TS girls was lower when compared with age-matched American untreated TS girls.

CONCLUSION:

This study presents the new body fat curves and reference values of body composition for untreated Egyptian TS adolescent girls. The present charts can be used for direct assessment of body FM % for Egyptian TS girls and evaluation for cases on GH treatment or other growth promoting therapy.     

Health and psychosocial status of patients with turner syndrome after transition to adulthood: the Belgian experience

BACKGROUND: Most girls with Turner syndrome (TS) are intensively followed by paediatricians, but are lost to follow-up when they reach adulthood. To gain insight into the adult medical and psychosocial situation, we performed a survey in young adult TS patients. PATIENTS AND METHODS: A questionnaire concerning current health status, education, occupation and living situation was sent to 160 young adult TS women, all treated during childhood with GH and oestrogen if needed. RESULTS: We received 102 completed questionnaires. Mean +/- SD age at reception of the questionnaire was 23.4 +/- 3.3 years, height 153.3 +/- 5.2 cm, body mass index 23.7 +/- 4.9 kg/m(2). Age and auxological parameters were comparable between responders and non-responders. Thirteen (12.7%) responders were not under regular medical care; 15 (14.7%) were seen by a general practitioner, while 28 (27.4%) needed several specialists. Forty-one (40.2%) patients reported health problems. The most frequently reported problem was hypertension (10.7%), followed by hypothyroidism (5.8%) and back problems (4.9%). Twenty-four (23.5%) of the 41 patients were taking medication for the indicated health problems. Twenty-six (25.5%) women had undergone spontaneous puberty; 16 of them reported spontaneous menstruations while 10 received oestrogen replacement therapy. Of the 76 women with induced puberty, 11 (14.5%) were not taking any oestrogen anymore. Compared with the general population, more TS women attended university and more obtained higher education. Forty-six women (45.1%) were working full-time, 7 (6.9%) were unemployed, and 4 (3.9%) received an allocation. Seventy (68.6%) patients were still living with their parents, while 18 (17.6%) were living together or married, and 14 (13.7%) were living alone. CONCLUSIONS: The transition of adolescents with TS to adult medical care is not optimal in Belgium. Although 40.2% of these young women reported health problems, 12.7% did not consult any physician. Many TS women did not take oestrogen replacement therapy. A specialized multidisciplinary approach for adults with TS is needed in order to optimize health and psychosocial status in these women.     

Total pubertal growth and markers of puberty onset in adolescents with GHD: comparison between mathematical growth analysis and pubertal staging methods

Two methods of determining puberty onset (Preece- Baines model 1 (PB1) and Tanner staging) were used to calculate total pubertal growth (TPG) in adolescents with growth hormone deficiency (GHD). PATIENTS AND METHODS: 34 patients (11 girls) met the following inclusion criteria: isolated GHD, >2 years growth hormone therapy prior to puberty onset, regular weight-adjusted GH dosage, known final height (age >21 years or height velocity <0.5 cm/year), no induction of puberty. PB1 was used to define age and height at onset of the pubertal growth spurt ("take-off"). RESULTS: The results (mean +/- SD) were as follows: in girls, mean age at take-off was 9.8 years; 2.0 +/- 1.1 years before breast stage B2. In boys, mean age at take-off was 11.3 years; 1.4 +/- 0.8 years before testes volume >3 ml. Height at take-off was lower than at Tanner stage 2 by 12.4 +/- 7.6 cm in girls and 7.7 +/- 5.3 cm in boys. TPG was thus markedly greater (p < 0.001) using the PB1 method, as compared with Tanner stage2. Peak height velocity was normal. Final height was -0.5 +/- 0.7 SDS in females and -0.4 +/- 0.9 SDS in males. CONCLUSIONS: The method of measuring TPG from take-off is more objective, and has potentially greater implications for GH therapeutics than the Tanner stage method. In our study, 40% of TPG occurred before "breast stage B2" was attained in GHD girls; whereas 23% of TPG occurred before "testes >3 ml" in GHD boys.     

Turner's syndrome--correlation between karyotype and phenotype

Turner's syndrome is defined as a congenital disease determining by quantitative and/or structural aberrations of one from two X chromosomes with frequent presence of mosaicism. Clinically it is characterized by growth and body proportion abnormalities, gonadal dysgenesis resulting in sexual infantilism, primary amenorrhoea, infertility, characteristic stigmata, anomalies of heart, renal and bones and the presence of some diseases like Hashimoto thyroiditis with hypothyroidism, diabetes mellitus type 2, osteoporosis, hypertension. Turner's syndrome occurs in 1:2000 to 1:2500 female livebirth. The most frequent X chromosome aberrations in patients with phenotype of Turner syndrome are as follows: X monosomy - 45,X; mosaicism (50-75%), including 45,X/46,XX (10-15%), 45,X/46,XY (2-6%), 45,X/46,X,i(Xq), 45,X/46,X,del(Xp), 45,X/46,XX/47,XXX; aberration of X structure: total or partial deletion of short arm of X chromosome (46,X,del(Xp)) isochromosom of long arm of X chromosome (46,X,(i(Xq)), ring chromosome (46, X,r(X)), marker chromosome (46,X+m). Searching of X chromosome and mapping and sequencing of genes located at this chromosome (such as SHOX, ODG2, VSPA, SOX 3) have made possible to look for linkage between phenotypes and adequate genes or regions of X chromosome. In this paper current data concerning correlation between phenotype and karyotype in patients with TS have been presented.     

Childhood Environment Influences Adrenarcheal Timing among First-Generation Bangladeshi Migrant Girls to the UK

Background

Adrenarche is a key early life event that marks middle childhood at approximately 7 years of age. Earlier work with British-Bangladeshi migrant women suggested that environmental conditions experienced before adrenarche influence adult reproductive function. We therefore investigated whether Bangladeshi children who migrate to the United Kingdom (UK) reach adrenarche earlier than non-migrants in Bangladesh or the United Kingdom.

Methods and Findings

Healthy girls, aged 5–16 years, were recruited from schools in Sylhet, Bangladesh and London, England comprising four groups: Sylhetis (n = 165), first-generation migrants to the United Kingdom (n = 42), second-generation girls (n = 162), and British girls of European origin (n = 50). Anthropometric measurements were collected together with questionnaire data for migration and socioeconomic characteristics. Saliva samples were assayed for dehydroepiandrosterone (DHEAS) using enzyme-linked immunosorbent assays. Multiple linear regressions tested for group differences in anthropometric and socioeconomic variables and DHEAS levels. Median ages at adrenarche (DHEAS>400 pg/ml) were estimated using Weibull regression models for parametric survival analysis. Hazard ratios for reaching adrenarche earlier and 95% confidence intervals (CI), both unadjusted and adjusted for anthropometric variables, were estimated from the survival analyses. First-generation migrants had a median age at adrenarche (5.3 years) that was significantly earlier than Sylheti (7.2), second-generation (7.4), and European (7.1) girls. In univariate analyses, first-generation girls reached adrenarche significantly earlier than Sylhetis [HR (CI): 2.8 (1.4–5.5]. In multivariate models, first generation girls still reached adrenarche earlier than Sylhetis after adjusting for height [HR(CI): 1.9 (0.9–4.1)] and weight [HR(CI):1.7 (0.8–3.8)], but these results were attenuated.

Conclusions

We suggest that rapid catch-up growth experienced by first generation girls during early childhood may explain their advanced adrenarche. The environmental conditions leading to an earlier adrenarche, as well as the health implications of this early transition, merit further exploration.     

Growth patterns and final height in congenital adrenal hyperplasia due to classical 21-hydroxylase deficiency. Results of a multicenter study

BACKGROUND: Longitudinal growth and bone age (BA) development are the most important clinical parameters for monitoring adequate glucocorticoid replacement in children with congenital adrenal hyperplasia (CAH). AIM OF THE STUDY: To analyze the growth pattern of patients treated for CAH of the salt wasting (SW) and simple virilizing (SV) clinical forms; to evaluate final height as compared to reference data and individual target height; to evaluate the course of BA development. PATIENTS AND METHODS: A large database of 598 patients with CAH was created in 5 Central European countries and growth data of 341 treated patients with 21-hydroxylase deficiency were analyzed retrospectively. The patients were of Caucasian origin. Centiles were constructed in a cross-sectional manner and an additional longitudinal analysis was performed in order to evaluate the pubertal growth spurt by applying particular statistical methods (Preece-Baines model). RESULTS: The growth of SW CAH patients was impaired in infancy and early childhood (0-3 years of age), but followed normal patterns in childhood until puberty. In contrast, children with SV CAH had normal patterns of growth in infancy and early childhood and were considerably taller than healthy references during childhood. In the longitudinal study, peak height velocity in both boys and girls was normal, but it occurred at an earlier age than in the standard population. The final height of patients with CAH was reduced in comparison to both the reference and the individual target height. No correlations were found between final height and age at the start of the therapy in SV patients or between final height and year of birth. BA was advanced in both types of CAH, but more accelerated in SV patients. CONCLUSION: Characteristic growth patterns for treated SV and SW CAH children were identified, with a normal pubertal growth spurt and reduced final height being observed.     

Prepubertal growth in children with long-term parenteral nutrition

In children who depend on long-term parenteral nutrition (PN), a major goal is to obtain optimal growth. The aim of this retrospective study was to analyze growth in children on long-term cyclic nocturnal home PN, over at least 8 years before puberty. Nine boys and 7 girls were studied. Their mean age at the time of study was 11 years with a mean PN duration of 10.5 (8.6-16.4) years. Diseases were short bowel syndrome (5), intractable diarrhea (4), chronic intestinal pseudo-obstruction (4) and long segment Hirschsprung's disease (3). In each child, periods of at least 2 years were analyzed: either periods of regular growth (R: height gain >50th percentile), or slow growth (S: height gain < or =25th percentile). Results were expressed as mean +/- SD. Comparisons were performed using either Student's test for unpaired data or Wilcoxon's test for paired data. PN provided a mean of 224 +/- 80 mg nitrogen/kg/day and 43 +/- 14 kcal/kg/day equivalent to 50% of recommended supplies. At the time of study, the population presented with weight (W) = -0.7 +/- 0.8 SD and height (H) = -1.5 +/- 1.3 SD. The difference between W and expected W for H (W/H) was significant (p < 0.002). W/H ratio was 105 +/- 11%. For the total PN duration, weight gain was +0.2 +/- 1.5 SD and height loss was -0.75 +/- 1.4 SD. An excess weight gain occurred in parallel with the deflection of height gain. Of the 16 children, regular prepubertal growth was achieved in 4 only. The other 12 showed alternate periods of R and S. In 8 of them, 26.5 years of R and 33.5 years of S were compared, each child being his own control. PN nitrogen and energy supplies were significantly higher during R periods than during S periods. In the absence of any disease or treatment explaining the failure to thrive, inadequate PN supplies, especially in terms of nitrogen supply, are thought to be responsible for a negative nitrogen balance and slowed growth. In case of any deflection away from the individual growth curve, it is recommended to adjust the PN supply early, especially nitrogen supply.