Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome.
ABSTRACT: OBJECTIVE:McCune-Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. DESIGN:Retrospective cohort analysis. METHODS:Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height and adult height. RESULTS:Twenty-eight girls received letrozole treatment. Treatment duration was 4.1?±?2.6 years (mean?±?1 s.d.) (range: 0.5-10.9) and mean follow-up was 6.0?±?3.3 years (range: 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole treatment was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (?BA/?CA) from 1.7 (IQR: 2.3) to 0.5 (IQR: 0.4) (P?
Project description:Objective:This study aimed to evaluate the differences in cephalometric characteristics and skeletal maturation in girls with central precocious puberty (CPP) via lateral and hand-wrist radiographs. We also aimed to identify the indicators that are most effective for determining skeletal maturity in these patients. Methods:The study included 70 Korean girls (mean age, 8.5 ± 0.5 years) diagnosed with CPP at the Department of Pediatrics, and 48 normal healthy age-matched girls who visited the Department of Orthodontics and had no history of hormone treatment or growth problems. Skeletal maturation was evaluated using lateral cephalometric and hand-wrist radiographs using cervical vertebrae maturation indicators (CVMI) and skeletal maturity indicators (SMI). Results:The mean mandibular plane angle was smaller in the CPP group than in the control group (35.8° ± 4.9° vs. 39.0° ± 6.5°), resulting in greater posterior facial height (p = 0.003). SMI was significantly greater in the CPP group (3.5 ± 1.4 vs. 2.0 ± 1.0) than in the control group (p = 0.001) and was significantly associated with CPP (r = 0.492; p = 0.001), whereas CVMI was not. Conclusions:In comparison with the control group, the CPP group exhibited a smaller mandibular plane angle, greater posterior facial height, and greater skeletal maturation. SMI may be more suitable than CVMI for determining skeletal maturation in CPP. Hand-wrist radiography is recommended in addition to lateral cephalogram for predicting growth in girls with CPP.
Project description:Background:The precision of adult height prediction by bone age determination in children with idiopathic growth hormone deficiency (IGHD) is unknown. Methods:The near adult height (NAH) of patients with IGHD in the KIGS database was compared retrospectively to adult height prediction calculated by the Bayley-Pinneau (BP) prediction based on bone age by Greulich-Pyle (GP) in 315 children and based on the Tanner-Whitehouse 2 (TW2) method in 121 children. Multiple linear regression analyses adjusted for age at GH start, age at puberty, mean dose and years of of GH treatment, and maximum GH peak in stimulation test were calculated. Results:The mean underestimation of adult height based on the BP method was at baseline 4.1 ± 0.7 cm in girls and 6.1 ± 0.6 cm in boys, at 1 year of GH treatment 2.5 ± 0.5 cm in girls and 0.9 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 0.4 ± 0.6 cm in girls and 3.8 ± 0.5 cm in boys. The mean underestimation of adult height based on the TW2 method was at baseline 5.3 ± 2.0 cm in girls and 7.9 ± 0.8 cm in boys, at 1 year of GH treatment adult height was overestimated in girls 0.1 ± 0.6 cm in girls and underestimated 4.1 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 3.1 ± 1.5 cm in girls and 3.6 ± 0.8 cm in boys. Conclusions:Height prediction by BP and TW2 at onset of GH treatment underestimates adult height in prepubertal IGHD children, while in mean 6 years after onset of GH treatment these prediction methods overestimated adult height.
Project description:<h4>Importance</h4>Prevention of osteoporosis in adulthood begins with optimizing bone health in early life. The longitudinal association between growth and bone accretion during childhood is not fully understood.<h4>Objectives</h4>To assess the acquisition of whole-body (WB) and skeletal site-specific bone mineral content (BMC) relative to linear growth in a healthy, diverse, longitudinal cohort of children, adolescents, and young adults and to test for differences related to sex and African American race.<h4>Design, setting, and participants</h4>This investigation was a mixed longitudinal study with annual assessments for up to 7 years at 5 US clinical centers. Participants were healthy children, adolescents, and young adults. The study dates were July 2002 through March 2010. The dates of the analysis were June through December 2016.<h4>Main outcomes and measures</h4>Anthropometrics, BMC, and body composition via dual-energy x-ray absorptiometry. The superimposition by translation and rotation (SITAR) analysis method was used to define the mean trajectories for height, WB lean soft tissue, appendicular lean soft tissue, and WB and skeletal site-specific BMC acquisition and to measure the age and magnitude of peak velocity for each parameter. The SITAR modeling was performed separately by sex and self-reported race.<h4>Results</h4>Among 2014 healthy children, adolescents, and young adults (1022 [50.7%] female and 479 [23.8%] African American) aged 5 to 19 years at study entry, the mean age of peak height velocity was 13.1 years (95% CI, 13.0-13.2 years) in African American boys vs 13.4 years (95% CI, 13.3-13.4 years) in non-African American boys (difference, -0.3 years; 95% CI, -0.4 to -0.1 years) and 11.0 years (95% CI, 10.8-11.1 years) in African American girls vs 11.6 years (95% CI, 11.5-11.6 years) in non-African American girls (difference, -0.6 years; 95% CI, -0.7 to -0.5 years). Age of peak acquisition of WB BMC was 14.0 years (95% CI, 13.8-14.1 years) in African American boys vs 14.0 years (95% CI, 13.9-14.1 years) in non-African American boys (difference, -0.0 years; 95% CI, -0.2 to 0.2 years) and 12.1 years (95% CI, 12.0-12.3 years) in African American girls vs 12.4 years (95% CI, 12.3-12.5 years) in non-African American girls (difference, -0.3 years; 95% CI, -0.4 to -0.1 years). At age 7 years, children had acquired 69.5% to 74.5% of maximal observed height but only 29.6% to 38.1% of maximal observed WB BMC. Adolescents gained 32.7% to 35.8% of maximal observed WB BMC during the 2 years before and 2 years after peak height velocity. Another 6.9% to 10.7% of maximal observed WB BMC occurred after linear growth had ceased. In the group at highest risk for fracture, non-African American boys, peak fracture incidence occurred approximately 1 year before peak height velocity.<h4>Conclusions and relevance</h4>In this longitudinal study, height gains substantially outpaced gains in BMC during childhood, which could contribute to fracture risk. A significant proportion of bone is accrued after adult height is achieved. Therefore, late adolescence represents a potentially underrecognized window of opportunity to optimize bone mass.
Project description:Skeletal age (SA) is considered the gold standard to assess the degree of maturation and has been widely used in sports, education and public health areas; however, it requires sophisticated equipment and well-trained technicians. Therefore, it is important to develop non-invasive methods for its evaluation. The aim was to develop an equation to predict SA using the percentage of adult height. SA was measured by Tanner-Whitehouse-3 method, and the percentage of adult height was estimated by two methodologies: Tanner-Whitehouse-3 method (P-TW3) and Khamis-Roche method (P-KR) using 839 schoolchildren of both sexes. Linear regression was used for predicting SA from P-TW3; then P-TW3 was replaced in the equation for P-KR value. Bland-Altman graphs, interclass correlation coefficient and Kappa index were used as validation tests. Model showed a SA predictive capacity of 93.2% in boys and 96.8% in girls. The average differences between SA measured and SA predicted by P-TW3 was 0.0504 (±?0.664) in boys and 0.0144 (±?0.435) in girls (P?=?0.229 and 0.667, respectively). When P-TW3 was replaced for P-KR value in the equation, the average differences were -?0.0532 in boys and 0.0850 in girls (P?=?0.509 and 0.167 respectively). The present model, based on the percentage of adult height, showed an adequate estimation of SA in children and adolescents and it can be used in the absence of bone X-ray equipment, in healthy boys aged 9 to 15 and girls 8 to 13.
Project description:A recommended field method to assess body composition in adolescent sprint athletes is currently lacking. Existing methods developed for non-athletic adolescents were not longitudinally validated and do not take maturation status into account. This longitudinal study compared two field methods, i.e., a Bio Impedance Analysis (BIA) and a skinfold based equation, with underwater densitometry to track body fat percentage relative to years from age at peak height velocity in adolescent sprint athletes. In this study, adolescent sprint athletes (34 girls, 35 boys) were measured every 6 months during 3 years (age at start = 14.8 ± 1.5 yrs in girls and 14.7 ± 1.9 yrs in boys). Body fat percentage was estimated in 3 different ways: 1) using BIA with the TANITA TBF 410; 2) using a skinfold based equation; 3) using underwater densitometry which was considered as the reference method. Height for age since birth was used to estimate age at peak height velocity. Cross-sectional analyses were performed using repeated measures ANOVA and Pearson correlations between measurement methods at each occasion. Data were analyzed longitudinally using a multilevel cross-classified model with the PROC Mixed procedure. In boys, compared to underwater densitometry, the skinfold based formula revealed comparable values for body fatness during the study period whereas BIA showed a different pattern leading to an overestimation of body fatness starting from 4 years after age at peak height velocity. In girls, both the skinfold based formula and BIA overestimated body fatness across the whole range of years from peak height velocity. The skinfold based method appears to give an acceptable estimation of body composition during growth as compared to underwater densitometry in male adolescent sprinters. In girls, caution is warranted when interpreting estimations of body fatness by both BIA and a skinfold based formula since both methods tend to give an overestimation.
Project description:The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height.We measured adult height in 943 of 1041 participants (90.6%) in the Childhood Asthma Management Program; adult height was determined at a mean (±SD) age of 24.9±2.7 years. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 ?g of budesonide, 16 mg of nedocromil, or placebo daily for 4 to 6 years. We calculated differences in adult height for each active treatment group, as compared with placebo, using multiple linear regression with adjustment for demographic characteristics, asthma features, and height at trial entry.Mean adult height was 1.2 cm lower (95% confidence interval [CI], -1.9 to -0.5) in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower (95% CI, -0.9 to 0.5) in the nedocromil group than in the placebo group (P=0.61). A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (-0.1 cm for each microgram per kilogram of body weight) (P=0.007). The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment (-1.3 cm; 95% CI, -1.7 to -0.9). During the first 2 years, decreased growth velocity in the budesonide group occurred primarily in prepubertal participants.The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative. (Funded by the National Heart, Lung, and Blood Institute and the National Center for Research Resources; CAMP ClinicalTrials.gov number, NCT00000575.).
Project description:<h4>Background</h4>Predicted maturity offset and age at peak height velocity are increasingly used with youth athletes, although validation studies of the equations indicated major limitations. The equations have since been modified and simplified.<h4>Objective</h4>The objective of this study was to validate the new maturity offset prediction equations in independent longitudinal samples of boys and girls.<h4>Methods</h4>Two new equations for boys with chronological age and sitting height and chronological age and stature as predictors, and one equation for girls with chronological age and stature as predictors were evaluated in serial data from the Wroc?aw Growth Study, 193 boys (aged 8-18 years) and 198 girls (aged 8-16 years). Observed age at peak height velocity for each youth was estimated with the Preece-Baines Model 1. The original prediction equations were included for comparison. Predicted age at peak height velocity was the difference between chronological age at prediction and maturity offset.<h4>Results</h4>Predicted ages at peak height velocity with the new equations approximated observed ages at peak height velocity in average maturing boys near the time of peak height velocity; a corresponding window for average maturing girls was not apparent. Compared with observed age at peak height velocity, predicted ages at peak height velocity with the new and original equations were consistently later in early maturing youth and earlier in late maturing youth of both sexes. Predicted ages at peak height velocity with the new equations had reduced variation compared with the original equations and especially observed ages at peak height velocity. Intra-individual variation in predicted ages at peak height velocity with all equations was considerable.<h4>Conclusion</h4>The new equations are useful for average maturing boys close to the time of peak height velocity; there does not appear to be a clear window for average maturing girls. The new and original equations have major limitations with early and late maturing boys and girls.
Project description:The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years.The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The kappa statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity.The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage>or=2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage>or=2. The prime determinant of height velocity was pubertal status.In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.
Project description:BACKGROUND:To evaluate the concordance of skeletal age (SA) with two predicted estimates of biological maturity status in elite British youth tennis players. METHOD:Participants were 71 male and female elite youth tennis players aged 8 to 16 years. Weight, height, and sitting height were measured. SA (Fels method) was the criterion indicator of maturity status. Maturity status was predicted with two methods: predicted age at peak height velocity and percentage of predicted adult height at the time of observation. Players were classified as late, average (on time), or early maturing with each method. Concordance of classifications was evaluated with kappa coefficients and Spearman's rank order correlations. RESULTS:Kappa coefficients between maturity status classifications were low in both sexes, - 0.11 to 0.22, while Spearman's rank order correlations between maturity status classifications based on SA and the percentage of predicted mature height were moderate in males (0.35) and females (0.25), but the corresponding correlations based on predicted age at peak height velocity (PHV) varied, moderate and negative in boys (- 0.37) and low and positive in girls (0.11). Concordance of maturity status classifications based on the prediction methods and SA among tennis players was thus limited. CONCLUSIONS:Maturity status based on the percentage of predicted mature height at the time of observation correlated better with maturity status based on SA in contrast to status based on predicted age at PHV in this sample of elite youth tennis players.
Project description:Reported mean ages, heights and weights of female soccer players aged <19 years in 161 studies spanning the years 1992-2020 were extracted from the literature or calculated from data available to the authors; 35 studies spanning the years 1981-2020 also included an indicator of biological maturation. Heights and weights were plotted relative to U.S. reference data. Preece-Baines Model 1 was fitted to moving averages to estimate ages at peak velocity. Maturity indicators included skeletal age, pubertal status, age at menarche, percentage of predicted adult height and predicted maturity offset. Heights and weights showed negligible secular variation across the time interval. Heights were slightly above or approximated the reference medians through 14 years old and then varied between the medians and 75th percentiles through 18 years old. Weights were above the reference medians from 9 to 18 years old. Mean ages at menarche ranged from 12.7 to 13.0 years. The trend in heights and weights suggested the persistence and/or selection of taller and heavier players during adolescence, while estimated age at peak height velocity (PHV) and ages at menarche were within the range of mean ages in European and North American samples. Data for skeletal and sexual maturity status were limited; predicted maturity offset increased linearly with mean ages and heights at prediction.