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Growth failure is a hallmark in children suffering from chronic kidney disease (CKD). It is most pronounced in children with congenital CKD requiring dialysis treatment. Optimal conservative management including adequate nutrition and growth hormone treatment, as well as early (preemptive) transplantation, is mandatory in order to reduce height deficit before transplantation. After transplantation the use of efficacious immunosuppressive strategies for an optimized graft function and early withdrawal, or even complete avoidance, of steroids are required to improve final height.

Мета дослідження: визначення показників зросту та кісткового віку дівчаток із синдромом Шерешевського — Тернера (СШТ) в українській популяції залежно від віку та каріотипу, кінцевого зросту порівняно зі здоровими дівчатами, а також визначення стану соматотропної функції гіпофіза дівчаток із СШТ.Матеріали і методи. Проведено ретроспективний аналіз за період з 2005 по 2014 рік 502 реєстраційних карт дівчаток із СШТ, віком від 11 місяців до 17 років включно. Поглиблене обстеження проводилось дітям, які проходили амбулаторне чи стаціонарне лікування в НДСЛ «ОХМАТДИТ» та Українському науково-практичному центрі ендокринної хірургії, трансплантації ендокринних органів і тканин. Визначали фізичний розвиток дитини, кістковий вік, наявність соматотропної недостатності, рівень інсуліноподібного фактора росту 1 (ІФР-1). Для порівняння показників зросту дітей із СШТ та здорових дівчаток загальної популяції ми використовували результати обстеження фізичного розвитку 525 соматично здорових дівчаток із нормальнім жіночим каріотипом віком від 10 місяців до 17 років включно (контрольна група). Результати. Різниця показників зросту в дівчаток із СШТ та соматично здорових дівчаток з нормальним жіночим каріотипом була вірогідною (p < 0,05) в усіх вікових групах старше одного року, збільшується з віком, максимальна в пубертатному віці. Ступень затримки зросту в дівчаток із СШТ у середньому становить –3,1 ± 1,1 SD з максимальним ступенем затримки в 14 років. Кістковий вік у дівчаток із СШТ затриманий в усіх вікових групах з максимальною різницею з паспортним віком у 17 років. Відсутня вірогідна різниця показників зросту, кісткового віку, рівня стимульованого СТГ та ІФР-1 у дівчаток із СШТ з різним каріотипом (p > 0,05), що свідчить про те, що формула каріотипу не впливає на ці показники. Більшість дівчаток із СШТ мають нормальну соматотропну функцію, однак у 35,7 % наявний частковій або повний дефіцит соматотропного гормона.

Objective The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature. Design Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis. Results All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups. Conclusion Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

The effectiveness of rhGH on growth and final height (FH) was determined in children with CKD and kidney failure using data linkage from two national databases. Data on Australian children with CKD and kidney failure treated with rhGH were obtained by linking ANZDATA and OzGrow registries. The CKD cohort included children treated with rhGH prior to kidney replacement therapy (KRT). The KRT cohort consisted of children with kidney failure, some received rhGH, and some were untreated. Height standard deviation scores (Ht-SDS) were calculated with final height defined as last height recorded in girls > 16 years of age and boys > 17 years of age. In the CKD group, there were 214 children treated with rhGH prior to KRT. In the KRT group, there were 1,032 children, 202 (19%) treated with rhGH and 830 (81%) untreated. Growth significantly improved in the rhGH-treated CKD group (ΔHt-SDS = +0.80 [+0.68 to +0.92]; p < 0.001) and the rhGH-treated KRT group (ΔHt-SDS = +0.38 [+0.27 to +0.50]; p < 0.001). Within the KRT cohort, final height was available for 423 patients (41%), of which 137 (32%) had been treated with rhGH. The rhGH-treated group demonstrated marginally better catch-up growth (ΔHt-SDS = +0.05 [−0.18 to 0.29]) compared to the non-rhGH-treated group (ΔHt-SDS = −0.03 [−0.16 to 0.10]; p = 0.49). This large linkage study confirms rhGH is effective in improving height in children with CKD pre-KRT. However, rhGH appears to have a variable impact on growth once children have commenced KRT resulting in a marginal impact on final height.

Background We evaluated pubertal growth and pubertal timing of participants born preterm compared to those born at term. Methods In the ESTER Preterm Birth Study, we collected growth data and measured final height of men/women born very or moderately preterm (n = 52/55), late preterm (34– Results Age at PHV (years) and PHV (cm/year) were similar in all gestational age groups. Compared to term controls, insignificant differences in age at PHV were 0.1 (95% CI: −0.2 to 0.4) years/0.2 (−0.1 to 0.4) for very or moderately/late preterm born men and −0.0 (−0.3 to 0.3)/−0.0 (−0.3 to 0.2) for women, respectively. Being born small for gestational age was not associated with pubertal growth. Age at menarche or voice break was similar in all the gestational age groups. Conclusions Timing of pubertal growth and age at menarche or voice break were similar in participants born preterm and at term. Impact Pubertal growth and pubertal timing were similar in preterm and term participants in a relatively large cohort with a wide range of gestational ages. Previous literature indicates that small for gestational age is a risk for early puberty in term born children. This was not shown in preterm children. While our study had limited power for children born very preterm, all children born preterm were not at increased risk for early puberty.

Growth hormone treatment for children with Prader Willi syndrome (PWS) has shown proven benefits not only in increasing final height but also with positive effects on body composition and motor development. In a recent letter to the editor, Hoybye and colleagues recommend growth hormone treatment for adults with PWS based exclusively on the genetic diagnosis and without regard for growth hormone secretory status. We question whether the benefits of growth hormone treatment in PWS adults, mainly improvement in body composition, are significant enough to justify the as yet unkown consequences of long-term treatment in an adult population. Morbidity and mortality in PWS are mainly due to complications of obesity, and growth hormone treatment does not result in a decrease in BMI or waist circumference. Increases in insulin-like factor-1 as a result of growth hormone treatment over the course of several decades in PWS adults raises concern over possible increase risk of cancer. Compliance with daily injections is likely to be poor. We suggest that efforts to provide appropriate dietary and exercise regimens may be more beneficial and cost-effective than advocating for growth hormone treatment for adults with PWS.

Objectives Gonadotropin-releasing hormone agonist treatment is important for optimal growth in girls with central precocious puberty (CPP). Data are lacking regarding benefit to height outcome when treatment is started after chronological age (CA) of 7 years, and if continued beyond CA of 10 years or bone age (BA) of 12 years. Methods Forty-eight girls with CPP were treated with monthly leuprolide depot. Change in predicted adult height (PAH) during treatment was assessed. Changes in PAH and growth velocity were compared between girls initiating treatment at CA Results Mean baseline CA was 6.8 years, BA, 10.2 years; and PAH, 156.4 cm. BA/CA ratio decreased from pretreatment values, averaging 1.5 to 1.2 at the end of treatment. Proportion of girls with >5 cm PAH change during treatment was similar, and PAH increased throughout treatment in most girls, regardless of age at treatment initiation. PAH continued to increase in 16/19 girls who continued treatment after BA of 12 years, and also in 16/22 girls who continued treatment after CA of 10 years. Conclusions PAH improved in most girls who initiated treatment after CA of 7 years. It continued to improve in most girls with longer treatment, even past BA of 12 years or CA of 10 years, which suggests that no absolute CA or BA limit should define initiation or end of treatment. Treatment plans need to be individualized, and neither treatment initiation nor cessation should be based on BA or CA alone.

OBJECTIVE Data about GnRHa on adult height in girls with central precocious puberty (CPP) have shown variable results, ranging from improvement of growth prognosis to lack of any benefit. This study was designed to delineate the criteria to decide which girls with idiopathic CPP (iCPP) will have a height benefit from GnRHa treatment. DESIGN Retrospective PATIENTS: 102 girls with iCPP who had reached final height (FH) were included. MEASUREMENTS Auxological, hormonal and radiological findings at treatment onset, and FHs were extracted from records. RESULTS Most important factor affecting height gain was chronological age (CA) at treatment onset. All the girls treated ≤6.4 years of age achieved a height gain of ≥1SDS, while none of the girls treated ≥8.3 years of age made the target. 75.6% of patients who started GnRHa between the ages of 6.4 and 8.3 years had a height gain of ≥1SDS. Most important factors affecting height gain in those treated 6.4-8.3 years were advanced bone age (BA), basal estradiol (E2 ) and pubertal stage (r2 : 0.906; P

Patients with childhood-onset systemic lupus erythematosus (cSLE) are at risk of becoming short adults. To evaluate the growth patterns and risk factors of short final height, a retrospective study was conducted in 97 patients (87 females, 90%) with cSLE who grew from the time of diagnosis and reached their final height. The primary outcome was the final height. Participants were divided into participants with short final height (final height standard deviation score (HSDS)- 2, n = 22, 23%) and participants with normal final height (final HSDS ≥ - 2, n = 75, 77%). At diagnosis, the mean age was 11.3 ± 2.4 years and HSDS was - 0.5 ± 1.3. The participants reached the final height of 1.51 ± 0.08 m (final HSDS - 1.3 ± 0.1) at mean age of 16.2 ± 2.3 years. The HSDS of participants with short final height steadily declined throughout the course of SLE (p = 0.02), and were significantly lower than participants with normal final height at any time point (p0.001). In participants with normal final height, HSDS significantly declined from baseline until 2 years after diagnosis (p = 0.01), and then became stable thereafter. The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.Conclusion: A substantial number of the participants with cSLE became short adults. Adequate nutrition and corticosteroid minimization should be emphasized in patients at high risk for short final height. What is known? • Growth failure is common in SLE due to many risk factors including chronic inflammation, malnutrition, and long-term use of corticosteroids. • In comparison to growth failure, final height is a better indicator of growth as the prevalence of growth failure is variable depending on definitions, patient age and pubertal status. What is new? • Nearly one fourth of children with SLE have short final height. • The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.

Introduction: About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. Materials and Methods: In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight Results: We included 252 patients with an average birth length of −2.0 ± 0.7 SD and birth weight of −1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from −2.2 ± 0.9 SD to −1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (p < 0.0001), GnRH analog therapy >2 years (p = 0.006), birth length (p < 0.02), height at the start of rhGH (p < 0.0001), IGF-1 level at the start of rhGH (p = 0.0002), growth velocity during the 1st year of treatment (p = 0.0002), and age and height at the onset of puberty (p < 0.0001, p = 0.0007, respectively). Conclusion: In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment.

To determine the effects of gonadotropin-releasing hormone analog treatment on final height and body mass index in girls with central precocious puberty.All cases with diagnosis age8 years constituted group 1 (n=19) and those with ≥8 years constituted group 2 (n=35).There was no significant difference in height standard deviation score, body mass index standard deviation score, bone age/chronologic age, predicted final height at the time of diagnosis, and follow-up between group 1 and group 2. There was no significant difference in final height (standard deviation score) between the groups. The number of obese and overweight cases at diagnosis and final height was similar. The target height (standard deviation score), predicted final height (standard deviation score), and final height (standard deviation score) were similar in both Group 1 and Group 2.We found that between the ages of 6-9.8 years, girls with central precocious puberty who received gonadotropin-releasing hormone analog treatment reached a final height within their target height range. It is concluded that gonadotropin-releasing hormone analog treatment increases body mass index during treatment and when patients reach the final height, they return to their pretreatment body mass index. Younger age and greater height at the time of diagnosis are the positive factors on final height.Santral erken puberteli olgularda Gonadotropin Releasing Hormon agonist tedavisinin final boy ve vücut kitle indeksi üzerine etkisinin değerlendirilmesini amaçladık.Çalışmaya alınan 54 kız hasta tanı yaşlarına göre 2 gruba ayrıldı. Tanı yaşı 8 yaş altı olan olgular Grup 1’i, 8 yaş ve üzeri olan olgular Grup 2’yi oluşturdu. Grup 1’de 19 hasta, Grup 2’de 35 hasta vardı.Tanıda ve izlem yıllarında boy standart deviasyon skoru, vücut kitle indeksi standart deviasyon skoru, kemik yaşı/takvim yaşı, öngörülen son boy açısından Grup 1 ile Grup 2 arasında istatistiksel olarak anlamlı fark yoktu. Gruplar arasında final boy, final boy standart deviasyon skoru açısından fark yoktu. Tanıda ve finalde obez ve kilolu olgu sayısı benzerdi. Hem Grup 1 hem Grup 2’de hedef boy, öngörülen son boy ve final boylar arasında ve bunların standart deviasyon skorları arasında istatistiksel olarak anlamlı fark saptanmadı.Bu çalışmada Gonadotropin Releasing Hormon agonist tedavisi verilen 6–9.8 yaş aralığındaki santral erken puberteli kızların hedef boyları ile uyumlu final boya ulaştıkları belirlendi. Gonadotropin Releasing Hormon agonist tedavisinin tedavi sırasında vücut kitle indeksini arttırdığı, tedavi kesiminden sonra final boya ulaşıldığında hastaların tanı vücut kitle indekslerine geri döndükleri sonucuna varıldı. Tanı yaşının küçük olması ve tanı boyunun uzun olması final boy üzerine pozitif etkili etmenler olduğu bulundu.

Objective The aim was to determine the final adult height (FAH) achieved by recombinant human growth hormone (rhGH) treatment, the factors affecting FAH and the success of attaining the genetic potential. Methods Data of 133 patients treated with rhGH therapy were reviewed retrospectively. Patients were grouped according to diagnosis, either isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD), and by sex, and pubertal status at the beginning of treatment. Results The mean age of initiation of treatment was 12.3±2.18 years, and the mean duration of rhGH treatment was 3.65±1.5 years. The mean height standard deviation score (SDS) at diagnosis was -3.11±0.75 SD. All patients received a standardized GH dose of 0.033 mg/kg/day. Mean FAH-SDS was -1.8±0.77 and delta height-SDS (the change in height SDS between the beginning and end of treatment) was 1.28±0.94 SD. FAH-SDS was -1.79±0.86 SD in males; -1.82±0.64 in females (p=0.857); -1.94±0.71 at the beginning of treatment in pubertal patients and -1.68±0.81 in prepubertal patients (p=0.056); -1.84±0.89 in patients with IGHD and -0.47±0.2 in patients with MPHD (p˃0.05). In multiple regression analysis, First year delta height-SDS was the most predictive factor for both FAH-SDS and delta height-SDS. Conclusion The majority of our patients achieved a final height compatible with their genetic potential as well as population standards when treated with rhGH even having started at a relatively late age. First year delta height-SDS was a predictive factor for FAH.

Study Design: Retrospective cohort study. Objectives: To explore the possibility of predicting final body height at maturity based on associating parameters at the time of diagnosing adolescent idiopathic scoliosis (AIS), while examining the effect of curve magnitude and deterioration. Methods: A total of 284 female patients with AIS (mean age 12.2 ± 1.1 years, 52.5% premenarchal) were followed till skeletal maturity, indicated by ≥Risser stage 4, static body height and arm span over the past 6 months, and postmenarche 2 years. Standing body height, arm span, menarchal status, Risser staging, distal radius and ulna (DRU) classification, Sanders staging (SS), Cobb angles (major and minor curves), and Lenke curve types at initial presentation were examined. Patients with/without curve deterioration were compared. Multiple linear regression was used for predicting final body height (cm), and remaining height increase (%). Results: Baseline body height was 152.1 ± 7.1 cm and major curve Cobb angle was 27.1° ± 7.4°, whereas at maturity they were 159.5 ± 5.4 cm and 32.5° ± 9.3°, respectively. For patients presented at Risser stage 0 or 1, radius grade (R) 6, ulnar grade (U) 5, or SS3, those with curve deterioration exhibited greater height increase potential at initial presentation ( P < .05) than those without deterioration. No intergroup difference was found for patients presented at ≥Risser 2, R7, U6, SS4. Predictive baseline parameters were age, body height, Cobb angle (major curve), curve type, and DRU grades. Prediction models of final body height ( R 2 = 0.735, P < .001) and remaining height increase ( R 2 = 0.742, P < .001) were established. Conclusions: Final body height prediction model was derived for female patients with AIS, with baseline body height and ulnar grading having larger impacts than other parameters.

Despite recent improvements in the composition of the diet, lower mineral bone density and overweight tendencies are incoherently described in patients with phenylketonuria (PKU). The impact of dietary factors and plasma phenylalanine levels on growth, BMI, body composition, and bone mineral density was investigated in our cohort of patients with hyperphenylalaninemia (HPA) with or without dietary treatment. The anthropometric, metabolic, BMI and other nutritional indicators and bone mineral density were compared between the group of 96 treated patients with PKU (58 classic PKU (cPKU) and 38 patients with moderate-mild PKU defined as non-classic PKU (non-cPKU)) and the untreated group of 62 patients with benign HPA. Having compared the treated and untreated groups, there were normal outcomes and no statistically significant differences in BMI, body composition, and bone mineral density. Lower body height standard deviation scores were observed in the treated as compared to the untreated group (P P = 0.012). Interestingly, the whole-body fat was statistically higher in non-cPKU as compared to cPKU patients. In conclusion, the dietary treatment ensured adequate nutrition without significant consequences in BMI, body composition, and bone mineral density. A low protein diet may have delayed the growth in childhood, but the treated patients gained a normal final height. Mild untreated hyperphenylalaninemia characteristic for benign HPA had no negative physiological effect on bone mineral density.

BACKGROUND Despite improved health, shorter stature is common in cystic fibrosis (CF). We aimed to describe height velocity (HV) and contribution of height-related genetic variants to height (HT) in CF. METHODS HV cohort: standard deviation scores (-Z) for HT, mid-parental height-adjusted HT (MPAH), and HV were generated using our Pediatric Center's CF Foundation registry data. HV-Z was compared with population means at each age (5-17 y), the relationship of HV-Z with HT-Z assessed, and HT-Z compared with MPAH-Z. GRS cohort: HT genetic risk-Z (HT-GRS-Z) were determined for pancreatic exocrine sufficient (PS) and insufficient (PI) youth and adults from our CF center and their relationships with HT-Z assessed. RESULTS HV cohort: average HV-Z was normal across ages in our cohort but was 1.5× lower (p

Introduction Protocol for prescribing hormone replacement therapy in isolated growth hormone (GH) deficiency includes magnetic resonance imaging of the brain. There is controversy on the frequency of structural pituitary abnormalities and on the importance of abnormal MRI findings on prognosis and response to GH replacement. Methods A descriptive, retrospective study of children of both sexes aged 0–14 years, who had undergone brain MRI, diagnosed with isolated GH deficiency at a tertiary hospital in the past 14 years, aimed at reporting the frequency of abnormal MRI findings in isolated GH deficiency, and to establish whether differences exist in height diagnosis and evolution according to MRI findings. MRI findings were also compared with the findings reported in healthy children in order to establish incidence. Results 96 patients were studied, of whom 74/96 (77%) reached adult age. Abnormal MRI findings were seen in 11.5% of them (8/11 of pituitary origin). No brain or pituitary tumor was seen in any case. Patients with abnormal images had a mean age at treatment start of 8 years, a target height of −0.8SD, and a final height of 1.04SD, while patients with normal MRI findings had an age at treatment start of 10 years old, a target height of −1.44SD, and a final height of −1.75SD, with statistically significant differences. Conclusions Patients with abnormal MRI findings show a more favorable response to GH replacement therapy.

ObjectiveThis study aimed to determine the most appropriate age for height control treatment in patients with Marfan syndrome (MFS).Materials and MethodsThis retrospective study included patients with MFS who underwent height control treatment with estradiol valerate. The estrogen dose was increased according to the height change. The cut-off age for the maximum difference between the expected height and actual final height was evaluated.ResultsSeventeen patients were included in this study. The difference between the height predicted by the growth curve and the final height (gcHtD) and that predicted by the bone age and the final height (baHtD) was the largest in the 10.5 years age group (p=0.0045 and p=0.0237, respectively). The gcHtD was 10.6 (10.2, 13.5) cm for patients aged ≤10.5 years, whereas it was 0.6 (−3.65, 5.85) cm for patients aged >10.5 years. The baHtD was 10.1 (7.31, 11.42) cm for patients aged ≤10.5 years, while it was 3.83 (0.84, 6.4) cm for patients aged >10.5 years. When height change was observed for a minimum of 6 months after completion of estrogen treatment, the average growth was 0.6 (0.2, 2.1) cm.ConclusionInitiating height control treatment before the age of 10.5 years is effective in female patients with MFS.

Objective To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male. Methods A national database was created. The data of patients were asked to be recorded in the data form. Results The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%. Conclusion It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage.

ObjectiveKnowledge of the biological parameters of pubertal growth spurt allows verification of secular changes and exploration of the timing of puberty. The aim of the study was to estimate final height, age at peak height velocity (APHV), and peak height velocity PHV (cm/y) in children and adolescents living at moderate altitude in Colombia.MethodsA cross-sectional study was designed in 2.295 schoolchildren from Bogotá (Colombia) with an age range from 5.0 to 18.9 years. Height (cm) was assessed. Preece–Baines model 1 (1PB) was used to make inferences about mathematical and biological parameters.ResultsThe five mathematical parameters estimated in general have reflected quality in the fit to the model, reflecting a small residual error. Final height was reached in boys at 170.8 ± 0.4 cm and in girls at 157.9 ± 0.2 cm. APHV was estimated at 12.71 ± 0.1 years in boys and 10.4 ± 0.2 years in girls. Girls reached APHV 2.2 years earlier than boys. In relation to PHV (cm/y), boys reached higher growth speed in height (7.4 ± 0.4 cm/y), and in girls it was (7.0 ± 0.2 cm/y).ConclusionIt was determined that final height was reached at 170.8 ± 0.4 cm in boys and 157.9 ± 0.2 cm in girls, and APHV (years) and PHV (cm/ye) were reached relatively early and with average peak velocity similar to Asian and Western populations. A large-scale longitudinal study is needed to confirm these findings.

BACKGROUND Accurate assessments of skeletal maturity is of critical importance to guide type and timing of orthopaedic surgical interventions. Several quantitative markers of the proximal tibia were recently developed using historical knee radiographs. The purpose of the present study was to determine which marker would be most effective in assessment of full-length radiographs in a modern pediatric patient population. METHODS All full-length radiographs at our institutions between 2013 and 2018 were reviewed. Inclusion criteria for our study required that the child reached final height as defined by 2 consecutive unchanged heights, at least 6 months apart, after age 16 for boys and 14 for girls. Patients with metabolic bone disease, prior surgery such as epiphysiodesis, or previous infections around the knee were excluded. Summary statistics for each of the 3 proximal tibial ratios were calculated and multiple linear regression was performed with percent of growth remaining as a dependent variable. A recommended regression model is presented and evaluated. RESULTS A total of 692 full-length radiographs met inclusion criteria. Proximal tibial ratios were calculated and averaged values for each percent of growth remaining was presented. Multiple linear regression demonstrated that using all 3 variables led to overfitting of the model so tibial metaphyseal width/lateral tibial epiphyseal height was selected as the optimal ratio for use by clinicians. The optimal model for determining growth was found to have R2=0.723 in the developmental set and R2=0.762 in an excluded validation set. CONCLUSIONS This study demonstrates that the proximal tibial metaphyseal width/lateral tibial epiphyseal height is the ideal measurement for clinicians seeking to determine growth remaining in children. It presents average values between 0% and 25% of growth remaining. This study also develops and validates a multivariable regression model for determining percentage of growth remaining in children that will allow for quantitative determination of growth using full-length radiographs. LEVEL OF EVIDENCE Level III.

BACKGROUND Though skeletal maturity is most relevant during adolescence, it has utility in treatment of younger patients in some circumstances. Accurate estimation of skeletal maturity using knee radiographs would be useful when treating limb length discrepancy and other general medical conditions in preadolescent patients. Currently, a quick, accurate, and reproducible method of estimating skeletal maturity in preadolescents is lacking. METHODS Serial anteroposterior knee radiographs taken at historical growth study visits leading up to the chronological age associated with 90% of final height (an enhanced skeletal maturity standard as compared with peak height velocity) were analyzed in 75 children. Epiphyseal and metaphyseal widths of the distal femur, proximal tibia, and proximal fibula were measured and the epiphyseal:metaphyseal ratio was calculated. Greulich and Pyle (GP) bone ages were also assigned by an experienced pediatric endocrinologist using left hand radiographs. Stepwise linear regression and generalized estimating equation analyses were used to make a skeletal maturity model incorporating demographics (age+sex) and knee epiphyseal:metaphyseal ratios. RESULTS A total of 258 left knee radiographs from 39 girls (mean age 8.6 y, range: 2.9 to 13 y) and 36 boys (mean age 10.6 y, range: 3.8 to 15 y) were included. The demographics+ratios model had similar prediction accuracy (0.49 vs. 0.48 y, P=0.84) and rate of outliers (11% vs. 9%, P=0.11) as the demographics+GP model. The demographics+ratios model outperformed all other models evaluated, including a demographics-only model (P

Poor glycemic control in children with type 1 diabetes (T1D) may hinder sexual development and the associated growth spurt. This study aims to identify factors that may affect the timing of puberty, total pubertal growth (TPG), and final height (F-Ht) in boys with T1D.This was a retrospective longitudinal study of 68 boys diagnosed with T1D during 1996 to 2009, who were prepubertal at diagnosis and had completed puberty at the time of data collection. Data were accessed regarding anthropometric measurements, Tanner stage, and glycosylated hemoglobin (HbA1c) levels from diagnosis to F-Ht. F-Ht was compared to parental height and Israeli National Health Survey data.The mean F-Ht standard deviation score (F-Ht-SDS) was lower than the mean Ht-SDS at diagnosis (P .006) but similar to the mean target height SDS (P = .3) and to values from the national survey (P = .12). Mean HbA1c levels in the year preceding pubertal onset were associated with the age at onset of puberty (R = 0.33, P = .009) and inversely with TPG (R = -0.3, P = .03). Mean HbA1c levels during puberty were inversely associated with TPG (R = -0.26, P = .035) and F-Ht (R = -0.28, P = .02). Boys who presented with diabetic ketoacidosis at diagnosis were shorter than those who did not throughout the follow-up.We found associations of age of pubertal onset, pubertal growth spurt, and F-Ht with target height and glycemic control before and during puberty. Targeted interventions to achieve optimal metabolic control during these time periods are needed for normal, timely puberty and for achieving optimal adult height within the genetic target height.背景: 1型糖尿病(T1D)儿童血糖控制不良可能会阻碍性发育和生长发育。本研究旨在确定可能影响T1D男孩青春期发育时间、总青春期发育(TPG)和最终身高(F-Ht)的因素。 方法: 这是一项回顾性纵向研究, 研究对象为1996年至2009年间被诊断为T1D的68名男孩, 他们在被诊断时处于青春期前, 在数据收集时青春期结束。获取从诊断到F-Ht的人体测量、Tanner分期和糖化血红蛋白(HbA1c)水平的数据。将F-Ht与父母身高和以色列国民健康调查数据进行比较。 结果: 诊断时F-Ht标准差得分(F-Ht-SDS)低于Ht-SDS平均值(P0.006), 与靶高度SDS平均值(P=0.3)和全国普查值(P=0.12)相近。青春期开始前一年的平均HbA1c水平与青春期开始年龄呈正相关(R=0.33, P=0.009), 与TPG呈负相关(R= -0.3, P=0.03)。青春期平均HbA1c水平与TPG(R=-0.26, P=0.035)和F-Ht(R=-0.28, P=0.02)呈负相关。在诊断时以糖尿病酮症酸中毒为起病的男孩在整个随访过程中的身高要比那些没有酮症酸中毒的男孩要矮。 结论: 我们发现青春期开始年龄、青春期生长增速期和F-Ht与青春期前和青春期期间的目标身高和血糖控制相关。在这些时间段内实现最佳代谢控制的针对性干预对于在遗传目标身高范围内达到最佳成人身高是必要的。.

Precocious puberty is the onset of puberty before the age of 8 years in girls and 9 years in boys. There is a global trend towards earlier onset of puberty. The prevalence is not known in Nigeria. Precocious puberty has implications such as inappropriate body appearance, psychological effects and decreased final height. This is a rare case report of a 3-year-old girl who presents with precocious puberty. Investigations did not reveal the cause. Investigations and treatment are expensive and a challenge in a poor resource setting. Early diagnosis and treatment are recommended to reduce the complications associated with it.

The UK Turner syndrome (TS) study examined the effect on final height of oxandrolone 0.05 mg/kg/day (maximum dose 2.5 mg) versus placebo from 9 years of age; and delaying ethinylestradiol induction of puberty by 2 years from 12 (E12) to 14 (E14) years in growth hormone-treated girls with TS. The study ran from 1999 to 2013. By 2011, eighty-two of 92 participants had reached final height and an interim analysis using the Super-Imposition by Translation And Rotation model showed significant increases in final height with both oxandrolone and E14. The analysis has been repeated now that all 92 patients have reached final height. Oxandrolone still significantly increased final height by 4.1 cm (95% CI 1.6 to 6.6, n=92) compared with 4.6 cm previously. However, the E14 effect was no longer significant at 2.7 cm (95% CI −0.8 to 6.1, n=56) compared with 3.8 cm previously.

A retrospective evaluation of growth in 112 patients (68 males, 44 females) with Hb E (HBB: c.79G>A)/β-thalassemia (β-thal), classified as 88 transfusion-dependent thalassemia (TDT) and 24 non tran...

Introducción: En los recién nacidos a término la recomendación universal es de que alimentados con leche materna exclusiva durante los primeros 6 meses de vida, sin embargo, con los prematuros no hay un acuerdo en la indicación de la lactancia; por considerarse que la leche materna sola no es suficiente. Numerosos estudios promueven el uso de fórmulas infantiles en prematuros, dado que se plantea que el prematuro debe mantener el mismo crecimiento como si estuvieran aún in utero.Métodos: Estudio de cohorte, se analizaron las historias clínicas de pacientes de los recién nacidos prematuros, que completaron el año de seguimiento en el programa madre canguro ambulatorio en el periodo comprendido entre 2006 a 2014. Se calcularon medidas de tendencia central y dispersión para las variables continuas, se aplicaron pruebas de confianza estadística.Resultados: Se obtuvo información de 90 prematuros; predominio de prematuro tardío (77%). El 16% de los bebés pesaron < 1500 gramos. Se encontró significancia estadística para el aumento en la talla final a los 12 meses para niños y niñas a favor de quienes recibieron leche materna hasta los 12 meses de edad corregida (p = 0,044).Conclusiones: Hay una diferencia estadísticamente significativa para el aumento en la talla final a los 12 meses para niños y niñas. Esto nos permite apreciar que al recibir lactancia materna los indicadores de desnutrición al año de edad corregida son comparativamente menores.

Clinicians generally use the term “tall stature” to define a height more than two standard deviations above the mean for age and sex. In most cases, these subjects present with familial tall stature or a constitutional advance of growth which is diagnosed by excluding the other conditions associated with overgrowth. Nevertheless, it is necessary to be able to identify situations in which tall stature or an accelerated growth rate indicate an underlying disorder. A careful physical evaluation allows the classification of tall patients into two groups: those with a normal appearance and those with an abnormal appearance including disproportion or dysmorphism. In the first case, the growth rate has to be evaluated and, if it is normal for age and sex, the subjects may be considered as having familial tall stature or constitutional advance of growth or they may be obese, while if the growth rate is increased, pubertal status and thyroid function should be evaluated. In turn, tall subjects having an abnormal appearance can be divided into proportionate and disproportionate syndromic patients. Before initiating further investigations, the clinician needs to perform both a careful physical examination and growth evaluation. To exclude pathological conditions, the cause of tall stature needs to be considered, although most children are healthy and generally do not require treatment to inhibit growth progression. In particular cases, familial tall stature subject can be treated by inducing puberty early and leading to a complete fusion of the epiphyses, so final height is reached. This review aims to provide proposals about the management of tall children.

Background: The effect on final height of gonadotropin-releasing hormone analogues (GnRHa) used in the treatment of precocious puberty is controversial. The aim of this study was to determine whether or not GnRHa therapy would make any contribution to final height in precocious puberty of girls with onset of pubertal characteristic development aged 6 - 8 years. Methods: Age at start of puberty, target height standard deviation score (SDS) presentation, follow-up height SDS, body mass index (BMI) SDS, bone age and predicted adult height of 34 female subjects who had reached their final height and with pubertal findings beginning at the ages of 6 - 8 were evaluated. These subjects were divided into two groups: treatment and non-treatment groups. The treatment group was further divided into two subgroups, receiving monthly or three-monthly depot GnRHa. Results: Age at onset of puberty was 7.2 ± 0.9 years. Twenty-five cases were started on GnRHa and nine were followed-up without treatment. Fourteen cases received monthly 3.75 mg depot triptorelin acetate and 11 received three-monthly 11.25 mg depot. Mean age at start of treatment in the treatment group was 9.1 ± 1.2 years and mean bone age was 9.7 ± 2.3 years. Age at presentation in the non-treatment group was 8.4 ± 1.4 years and bone age was 10.3 ± 2.1 years. Target and final height SDS were similar in all the groups (P > 0.05). No difference was determined between the treatment groups in terms of initial height SDS, bone age, length of treatment, final height SDS or BMI SDS (P > 0.05). Conclusions: GnRHa therapy did not make a positive contribution to final height in precocious puberty of girls with onset of puberty aged 6 - 8 years. J Clin Med Res. 2019;11(2):133-136 doi: https://doi.org/10.14740/jocmr3710

Objective Multiple endocrine neoplasia 2B (MEN2B) is characterised by early-onset medullary thyroid carcinoma (MTC), pheochromocytoma and several nonendocrine manifestations. Unfortunately, MEN2B is often diagnosed late, after the development of clinically significant MTC. Marfanoid habitus is considered an important related feature, which may lead to the assumption that patients with MEN2B have tall stature. Here, we describe the longitudinal growth and body proportions of eight MEN2B patients during childhood. Design It is a retrospective case series. Methods Patients were under the care of a Dutch MEN expertise centre. Growth patterns were assessed and interpreted in relation to body mass index (BMI), age at diagnosis and at thyroidectomy, extensiveness of disease manifestations and parental height. Results Seven patients were short during childhood, of whom four showed growth below target height range (THR) and three at the lowest margin of THR. Only one patient grew well within THR. All patients who attained final height (n = 4) ended within THR, despite short stature during childhood. Arm span/height ratio was not increased and upper segment/lower segment ratio was not reduced in any patient. Short stature in childhood in this study did not seem to be associated with age at diagnosis, age at thyroidectomy, extensiveness of MTC, endocrine deficiencies or BMI. Conclusions This study shows that children with MEN2B may well present with short rather than tall stature. Thereafter, final height within THR was attained in those who already reached adulthood, but none had tall stature. Finally, body proportions were normal in all children and adults in this case series, not underlining a 'marfanoid' body habitus.

BackgroundThe growth potential of pubertal short stature boys is limited by the effect of estrogen on epiphyseal fusion. This study aims to identify the efficacy and safety of growth hormone (GH) combination with letrozole on final adult height (FAH) in pubertal short stature boys. MethodsThis is a retrospective study. Among pubertal short stature boys who treated with GH and letrozole were be followed up in our hospital, 20 cases reached FAH. ResultsBaseline chronological age were 12.12±1.14yr, bone age were 13.00±0.93yr. The treatment duration was 1.94±0.67yr. The height standard deviation score for bone age was increased from -1.46±0.51 to -0.12±0.57 (p

Young children starting kidney replacement therapy (KRT) suffer high disease burden with unique impacts on growth and development, timing of transplantation and long-term survival. Contemporary long-term outcome data and how these relate to patient characteristics are necessary for shared decision-making with families, to identify modifiable risk factors and inform future research. We examined outcomes of all children ≤ 5 years enrolled in the Australia and New Zealand Dialysis and Transplant Registry, commencing KRT 1980–2017. Primary outcomes were patient and graft survival. Final height attained was also examined. We used generalized additive modelling to investigate the relationship between age and graft loss over time post-transplant. In total, 388 children were included, of whom 322 (83%) received a kidney transplant. Cumulative 1-, 5- and 10-year patient survival probabilities were 93%, 86% and 83%, respectively. Death censored graft survival at 1, 5 and 10 years was 93%, 87% and 77%, respectively. Most children were at least 10 kg at transplantation (n = 302; 96%). A non-linear relationship between age at transplantation and graft loss was observed, dependent on time post-transplant, with increased risk of graft loss among youngest recipients both initially following transplantation and subsequently during adolescence. Graft and patient survival have improved in recent era. Young children commencing KRT have good long-term survival and graft outcomes. Early graft loss is no reason to postpone transplantation beyond 10 kg, and among even the youngest recipients, late graft loss risk in adolescence remains one of the greatest barriers to improving long-term outcomes.

Restriction of physical growth and development is a known problem in patients with juvenile idiopathic arthritis (JIA). However, the effect of medical treatment for JIA on skeletal growth in affected children has not been properly investigated. We, therefore, hypothesize that naproxen and methotrexate (MTX) affect endochondral ossification and will lead to reduced skeletal development. Treatment of ATDC5 cells, an in vitro model for endochondral ossification, with naproxen or MTX resulted in increased chondrogenic but decreased hypertrophic differentiation. In vivo, healthy growing C57BL/6 mice were treated with naproxen, MTX, or placebo for 10 weeks. At 15 weeks postnatal, both the length of the tibia and the length of the femur were significantly reduced in the naproxen‐ and MTX‐treated mice compared to their controls. Growth plate analysis revealed a significantly thicker proliferative zone, while the hypertrophic zone was significantly thinner in both experimental groups compared to their controls, comparable to the in vitro results. Micro‐computed tomography analysis of the subchondral bone region directly below the growth disc showed significantly altered bone microarchitecture in naproxen and MTX groups. In addition, the involvement of the PTHrP‐Ihh loop in naproxen‐ and MTX‐treated cells was shown. Overall, these results demonstrate that naproxen and MTX have a profound effect on endochondral ossification during growth plate development, abnormal subchondral bone morphology, and reduced bone length. A better understanding of how medication influences the development of the growth plate will improve understanding of endochondral ossification and reveal possibilities to improve the treatment of pediatric patients.

Aim: It is known that chronic malnutrition observed in the early childhood creates many negative results in adult life. Studies examining the effects of nutritional deficiency experienced at older ages and in adolescence are quite limited. In other words, the long-term consequences of nutritional defect in acute/ chronic moderate or mild malnutrition patients still remains important as an issue to be investigated. For this purpose; In this study, it was aimed to determine the final adult height (predicted adult height) of children and adolescents with different age distribution and who were diagnosed with malnutrition as a result of nutritional-endocrinological anthropometric evaluations, and to compare these data with their genetic potential. Material and Methods: The study included 21 cases diagnosed with malnutrition in the pediatric endocrinology department. After the detailed history of the cases, anthropometric measurements and physical examination, biochemistry, hormonal and micronutritional status, celiac antibody levels were evaluated. In the anthropometric evaluation of all cases, body weight, height, height deviation, bone age, target height, target height deviation parameters were used. Patients’ pubertal development was determined according to Tanner-Marshall staging. In the determination of the nutritional status of the patients, data including Weight for Age (WA), Height for Age (HA) and Weight for Height (WH) were used as a nutritional anthropometric measurement using the Gomez-Waterlow classification. In addition, the predicted adult height was calculated with special formulas based on skeletal ages in all cases. Predicted adult height data were obtained using Bayley N Pinneau tables. Results: Of the 21 cases with an average age of 9.81±4.34 years, 12 were prepubertal and 9 were pubertal. Acute episode over chronic malnutrition was found in 19 cases, chronic in 2 cases and acute malnutrition in one case. Considering the severity of malnutrition; WA parameter was determined as severe malnutrition in 1 case, mild-moderate malnutrition in 20 cases, HA parameter was determined as normal in 12 cases, mild-moderate malnutrition in 9 cases, WH parameter was determined as normal in 3 cases, mild-moderate malnutrition in 18 cases. While the predicted adult height of all cases was 164.89±7.96 cm, the target height average of these cases was 166.5±8.09 cm. It was observed that the predicted adult height compared to the target height was the lowest in the chronic group. In seven cases with bone age below 6 years of age, the actual height deviations were distinctly behind the target height deviation. All of these cases were compatible with chronic malnutrition. Conclusion: These results are valuable in terms of showing that malnutrition experienced in any period of growth may negatively affect the predicted adult height. On the other hand, this research; It emphasizes the importance of nutritional anthropometry in all cases with or without short stature. In addition, in another study we conducted in 11 adolescents, it was found that nutritional defect negatively affected growth by decreasing IGF1/IGFBP3 levels, and growth factors increased and growth was supported in the cases that were nutritionally supported. In this study, if the nutritional deficiency is not replaced in patients with malnutrition, it suggests that even if the actual height is not affected, there will be retardation in the final height of the patients.

Growth retardation is a major complication in children with chronic kidney disease (CKD) and on kidney replacement therapy (KRT). Conversely, better growth in childhood CKD is associated with an improvement in several hard morbidity–mortality endpoints. Data from pediatric international registries has demonstrated that improvements in the overall conservative management of CKD, the search for optimal dialysis, and advances in immunosuppression and kidney transplant techniques have led to a significant improvement of final height over time. Infancy still remains a critical period for adequate linear growth, and the loss of stature during the first years of life influences final height. Preliminary new original data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry confirm an association between the final height and the height attained at 2 years in children on KRT.

Objectives: Sex steroids, administered as a priming before GH stimulation tests (GHST) to differentiate between growth hormone deficiency (GHD) and constitutional delay of growth and puberty (CDGP) or as growth-promoting therapy using low-dose sex steroids (LDSS) in CDGP, are much debated. We aimed to compare auxological outcomes of CDGP or GHD children undergoing primed or unprimed GHST and to evaluate LDSS treatment in CDGP. Design: Retrospective study among three paediatric University Hospitals in Italy and UK. Methods: 184 children (72 females) aged 12.4±2.08years underwent primed (/P+) or unprimed (/P−) GHST and were followed up until final height (FH). CDGP patients were untreated (CDG P−) or received LDSS (CDGP+). The cohort included 34 CDG P−/P+, 12 CDGP+/P+, 51 GHD/P+, 29 CDG P−/P−, 2 CDGP+/P− and 56 GHD/P−. FH standard deviation score (SDS), Δ SDS FH-target height (TH) and degree of success (−1≤Δ SDS FH-SDS TH ≤ +1) were outcomes of interest. Results: GHD/P+ had better FH-SDS (−0.87 vs −1.49; P=.023) and ΔSDS FH-TH (−0.35 vs −0.77; P=.002) than CDGP−/P+. Overall, GHD/P+ showed the highest degree of success (90%, P=.006). Regardless of priming, both rhGH and LDSS improved degree of success compared to no treatment (89% and 86% vs 63%, P=.0009). GHD/P+ showed a trend towards a higher proportion of permanent GHD compared to GHD/P- (30.43% vs 15.09%; P=.067). Conclusion: In peripubertal children, priming before GHST improves diagnostic accuracy of GHST for idiopathic GHD. LDSS treatment improves auxological outcomes in CDGP.

Introduction : Turner syndrome (TS) is a rare disease with typical phenotype manifestations and short stature. Part of the therapy in TS patients is the recombinant human growth hormone (rhGH) that leads to improved height velocity and final height. Aim : The aim of the current study is to summarize the results of the diagnosis and treatment with rhGH of the TS patients followed up at a tertiary university center from 2011 to 2020. Patients and Methods : The study design is a retrospective cohort evaluation. All study participants had at least one full year of observation at the center. A total of 28 children with genetically confirmed TS or TS variation karyotype, aged between 2 and 18 years, 92.9 % of whom were girls, participated in the study. Results : The mean age at diagnosis was 9.6±3.7 years. Therapy with rhGH was started at 9.27±3.4 years in 22 (78.5%) of them with a mean rhGH dose of 0.035±0.006 mg/kg/d, which led to height gain of 8.0±1.3 cm for the first year. With a similar rhGH dose for the 2 nd year of treatment (0.033±0.007 mg/kg/d), height velocity of 6.8±1.1 cm was achieved (p

Purpose: Growth hormone deficiency (GHD) is the most prevalent hypothalamic–pituitary (HP) disorder found in childhood cancer survivors (CCS). The published studies assessing GHD in CCS concluded that recombinant human GH (rhGH) does not restore final height (FH) to that predicted from mid-parental height (MPH). Thus, wider analyses on final height outcomes after rhGH in CCS are needed. Methods: Retrospective study on final height (FH) in 87 CCS treated with rhGH. Patients were divided into: Group A (n =48) who underwent cranial radiotherapy or had non-irradiated tumours of HP area, and B (n =39) who were treated with craniospinal or total body irradiation (TBI). 19/87 patients with central precocious/early puberty also received GnRH analogues. Results: Height (HT) gain after 1 and 2years of rhGH was 0.38 ± 0.35SDS and 0.18 ± 0.30SDS, respectively (P < 0.0001); mean FH was in the normal range (− 0.85 ± 1.34SDS), though not significantly different from HT SDS at baseline. 67% overall failed to reach MPH especially in Group B (P < 0.0001). However, height loss (HT SDS-MPH SDS) at FH improved or remained stable compared to baseline in 26/45 patients (58%). On stepwise regression analysis, major determinants of FH were HT at baseline (P < 0.0001) and delay before start of rhGH (P = 0.012). There was no significant difference in FH when GnRHa was added to rhGH. Conclusion: rhGH and GnRH analogues therapy, when indicated, though failing to induce catch-up growth, prevented further height loss leading to a FH within the normal range but still below MPH, this latter being statistically significant in children who received craniospinal and TBI.

Puberty in children with Prader-Willi syndrome (PWS) is usually delayed and/or incomplete but in some patients premature/early adrenarche is observed. We assessed the premature adrenarche (PA) in PWS patients during the recombinant human growth hormone (rhGH) therapy and influence of PA on the course of central puberty (CP), rhGH efficacy and safety, and patients&rsquo, metabolic state. Forty-nine PWS patients were treated with rhGH, 11 presented with PA (group 1) and 14 had normal course of adrenarche (group 2). PA was observed in 22.5% of the PWS children treated with rhGH. The mean time between the rhGH start and the adrenarche, the rhGH dose, the growth velocity and the insulin-like growth factor 1 SD (IGF1 SD) during the treatment, as well as the time of CP, final height SD and BMI SD were similar in both groups. There were also no significant differences in the metabolic assessment&mdash, the oral glucose tolerance test (OGTT) and lipid profile results. PA may be a part of the clinical picture of PWS, apart from hypogonadotrophic hypogonadism and it seems to have no influence on CP in PWS patients. The rhGH efficacy and safety were comparable in the patients with PA and the normal course of adrenarche.

Objectives This study aimed to ascertain if there is a defined pattern of injury related to the percentage of attained adult height and classify injuries according to maturity status bands. Design Prospective cohort study. Methods From 1998–2019, 63 elite male soccer players of at least the U12 category from a Spanish LaLiga club’s academy were followed until reaching their final height. Medical staff recorded injuries following the FIFA consensus and measured height 2–3 times per season. The percentage of adult height at which each injury occurred was calculated using the player’s closest height to the injury and his final adult height. Injuries were classified in maturity bands, pre-peak-height-velocity (PHV) 96%. Results There were 509 injuries among the 63 players. Growth-related injuries occurred at a median (IQR) of 91.2% (86.7%–95.2%) of adult height, predominating in pre-PHV and PHV bands. Muscle injuries predominantly occurred at post-PHV, with 77.78% of those conditions occurring within that time frame and at 98.7% (96%–99.5%) of adult height. Likewise, knee and ankle joint/ligament injuries predominated at post-PHV (87% and 65% of total cases, respectively) occurring at 99.0% (97.9%–99.9%) and 98.4% (89.2%–99.4%) of adult height, respectively. Conclusions Injuries follow a specific pattern according to the percentage of adult height.

BACKGROUND The creation of accurate markers for skeletal maturity has been of significant interest to orthopaedic surgeons. They guide the management of diverse disorders such as adolescent idiopathic scoliosis, leg length discrepancy, cruciate ligament injuries, and slipped capital femoral epiphysis. Multiple systems have been described to predict growth using radiographic skeletal markers; however, no such system has yet been developed for the proximal tibia. The purpose of this study was to establish quantitative radiographic parameters within the proximal tibia that can be used to assess degree of skeletal maturity. METHODS From the Bolton Brush collection, 94 children, consisting of 49 girls and 4 boys between the ages of 3 and 18 years old, were followed annually throughout growth with serial radiographs and physical examinations. Final height at maturity was used to calculate the growth remaining at each visit. Multiple measurements for each knee radiograph were performed and correlated with the percentage of growth remaining. Tibial epiphysis width, tibial metaphysis width, and height of the lateral tibial epiphysis were measured on each film and the composite ratios between each of these sets of variables along with their respective accuracy and reliability were calculated. Single and multiple linear regression models were constructed to determine accuracy of prediction. Interobserver and intraobserver studies were performed with 4 investigators ranging from medical student to senior attending and calculated using the intraclass correlation coefficient. All 4 examiners measured all of the subjects and the ratios created were averaged. RESULTS Tibial epiphysis width, tibial metaphysis width, and height of the lateral tibial epiphysis were all found to be strongly correlated with growth remaining with R values ranging from 0.57 to 0.84. In addition, all 3 ratios were found to be reliable with intraobserver and interobserver intraclass correlation coefficients ranging from 0.92 to 0.94 and 0.80 to 0.94, respectively. A multiple linear regression model demonstrated that combining these 3 ratios allows for a predictive R value of 0.917, showing that these ratios when combined were highly predictive of growth remaining. All findings were independent of sex (P=0.996). CONCLUSIONS We describe 3 measurements that can easily be obtained on an anteroposterior radiograph of the knee. We demonstrate that ratios of these variables can be measured reliably and correlate closely with remaining growth, independent of sex. Together, we believe that these factors will improve the accuracy of determining growth from lower extremity radiographs that include the proximal tibia. CLINICAL RELEVANCE This study provides a new quantitative technique to evaluate growth in the lower extremity, which can inform a range of conditions including adolescent idiopathic scoliosis, leg length discrepancy, cruciate ligament injury, and slipped capital femoral epiphyses.

Objetivo: evaluar el efecto de los análogos de GnRH sobre la predicción de talla final adulta en niñas con pubertad precoz central de diagnóstico tardío. Materiales y métodos: estudio descriptivo, retrospectivo. Se incluyeron niñas atendidas entre 2012 y 2018 en la Unidad de Endocrinología Pediátrica del Hospital Cayetano Heredia con diagnóstico de pubertad precoz central idiopática de diagnóstico tardío. Se realizó evaluación antropométrica, evaluación de estadío Tanner y determinación de edad ósea con el método de Greulich y Pyle, estimando la predicción de talla final adulta mediante el método de Bayley Pinneau antes y después del tratamiento con análogos de GnRH. Se realizó t de student para comparar la predicción de talla antes y después del tratamiento. Se consideró significativo un p< 0,05. Resultados: se incluyeron 23 niñas con edad cronológica media de 8,4 ± 0,4 años y una edad ósea de 10,7 ± 0,8 años al ingreso. El 83,9% de las pacientes tuvieron exceso de peso y el 74,0% estadio Tanner 3 al diagnóstico. El tiempo promedio de tratamiento con análogos de GnRH fue de 20,5 ± 8,4 meses. El efecto del tratamiento calculado con la diferencia de predicción de talla final adulta menos predicción de talla inicial fue de 2,5 ± 4,1 cm (p

Context GnRHa treatment has been a standard of care in progressive early puberty (EP). Choice of the GnRHa formulation is dependent on the preference of the clinician. Objective To compare the effects of triptorelin acetate (TA) and leuprolide acetate (LA) on anthropometry in girls with EP. Design A descriptive observational study. Subjects and methods Girls diagnosed with central EP and treated with GnRHa at least for one year were included; treated with TA (n=46) and LA (n=35). First year anthropometric response and final height were evaluated. Results The mean age at the initiation of GnRHa treatment of girls was 8.5±0.5 years. The ratio of obesity and of overweight was 7.4 and 25.9%, respectively. In both TA and LA groups, anthropometric data of the patients at initiation and at the first year of treatment were similar. Although growth velocity was similar in each group, in LA group height SDS at the first year of the treatment showed a significant decrease (p=0.045), but not in TA group (p=0.317). No significant ΔBMI was observed with treatment. The differences between FH - PAH at initiation (height gain) in TA and LA groups were 2.9±4.7 and 4.0±5.8 cm, respectively (p=.316). Height gain per treatment year was 1.7±3.0 cm. Conclusions There was a significant decrease in height SDS at the first year of leuprolid treatment, but not in triptorelin. Although these two analogs show similar effects on treatment, a not significant but slightly better benefit in leuprolide was observed.

Background: The management of children and adolescents with chronic kidney disease (CKD) and growth failure candidate for recombinant human growth hormone therapy (rhGH) is based on an appraisal of the literature established on a 2006 consensus statement and 2019 Clinical practice recommendations. The performance of these guidelines has never been tested. Aims: The objective of this study was to establish the level of adherence to international guidelines based on the 2006 consensus and the 2019 criteria that lead to the initiation of growth hormone treatment by both pediatric endocrinologists and pediatric nephrologists. Methods: A multidisciplinary team of pediatric endocrinologists and pediatric nephrologists, members of the Italian Society of Pediatric Endocrinology or of the Italian Society of Pediatric Nephrology, discussed and reviewed the main issues related to the management of pediatric patients with CKD who need treatment with rhGH. Experts developed 11 questions focusing on risk assessment and decision makings in October 2019 and a survey was sent to forty pediatric endocrinologists (n = 20) and nephrologists (n = 20) covering the whole national territory. The results were then analyzed and discussed in light of current clinical practice guidelines and recent recommendations. Results: Responses were received from 32 of the 40 invited specialists, 17 of whom were pediatric endocrinologists (42.5%) and 15 pediatric nephrologists (37.5%). Although all the centers that participated in the survey agreed to follow the clinical and biochemical diagnostic work-up and the criteria for the treatment of patients with CKD, among the Italian centers there was a wide variety of decision-making processes. Conclusions: Despite current guidelines for the management of children with CKD and growth failure, its use varies widely between centers and rhGH is prescribed in a relatively small number of patients and rarely after kidney transplantation. Several raised issues are not taken into account by international guidelines and a multidisciplinary approach with mutual collaboration between specialists will improve patient care based on their unmet needs.

Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (− 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001–0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) &lt, &minus, 3.0, GH peak in stimulation tests (stimGH) &ge, 10.0 &micro, g/L, IGF-I &lt, 2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGFGT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them.

Background: Given the rarity of 11β-hydroxylase deficiency (11βOHD), there is a paucity of the data about the differences in clinical and biochemical characteristics of classic (C-11βOHD) and non-classic 11βOHD (NC-11βOHD).Objective: To characterize a multicenter pediatric cohort with 11βOHD. Method: The clinical and biochemical characteristics were retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. Results: 102 patients (C-11βOHD; n=92, NC-11βOHD; n=10) from 76 families (46,XX; n=53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female final height was 152 cm (-1.85SDS) and male 160.4 cm (-2.56SDS). None of the NC-11βOHD girls had ambiguous genitalia (C-11βOHD 100%) and none of the NC-11βOHD patients were hypertensive (C-11βOHD 50%). Compared to NC-11βOHD, C-11βOHD patients were diagnosed earlier (1.33 vs. 6.9 years, p 2.2

Context Pituitary hormonal deficiencies in patients with craniopharyngioma may impair their bone health. Objective To investigate bone health in patients with craniopharyngioma. Design Retrospective cross-sectional study. Setting Dutch and Swedish referral centers. Patients Patients with craniopharyngioma (n = 177) with available data on bone health after a median follow-up of 16 years (range, 1-62) were included (106 [60%] Dutch, 93 [53%] male, 84 [48%] childhood-onset disease). Main outcome measures Fractures, dual X-ray absorptiometry-derived bone mineral density (BMD), and final height were evaluated. Low BMD was defined as T- or Z-score ≤-1 and very low BMD as ≤-2.5 or ≤-2.0, respectively. Results Fractures occurred in 31 patients (18%) and were more frequent in men than in women (26% vs. 8%, P = .002). Mean BMD was normal (Z-score total body 0.1 [range, -4.1 to 3.5]) but T- or Z-score ≤-1 occurred in 47 (50%) patients and T-score ≤-2.5 or Z-score ≤-2.0 in 22 (24%) patients. Men received less often treatment for low BMD than women (7% vs. 18%, P = .02). Female sex (OR 0.3, P = .004) and surgery (odds ratio [OR], 0.2; P = .01) were both independent protective factors for fractures, whereas antiepileptic medication was a risk factor (OR, 3.6; P = .03), whereas T-score ≤-2.5 or Z-score ≤-2.0 was not (OR, 2.1; P = .21). Mean final height was normal and did not differ between men and women, or adulthood and childhood-onset patients. Conclusions Men with craniopharyngioma are at higher risk than women for fractures. In patients with craniopharyngioma, a very low BMD (T-score ≤-2.5 or Z-score ≤-2.0) seems not to be a good predictor for fracture risk.

Hypochondroplasia is a cause of disproportionate short stature and characterized by minor clinical manifestations. The aim of this study was to evaluate the efficacy of long-term growth hormone (GH) therapy in hypochondroplastic cases with inadequate response to GH stimulation tests. In this study, six patients who had a height standard deviation score of -3.43 before the treatment and a mean age of 7.42 years and who had received GH treatment at a dose of 0.2 mg/kg/week for a mean period of 4.45 years were evaluated. A good response was found in the first year of treatment, but this increase was not found to be sufficient for the patients to achieve an adequate final height.

OBJECTIVES The aims of this study were to describe changes in height during childhood and to investigate potential changes in the proportion of children attaining final height in childhood and in correlations between child and adult height across birth cohorts. METHODS We included 363 059 children (179 906 girls) from the Copenhagen School Health Records Register, who were born between 1930 and 1989, with height measurements at ages 7, 10, or 13 years. Linkages to data resources containing adult height values between ages 18 and 69 years were possible for a subpopulation of 96 133 individuals (23 051 women). Birth years were categorized as 1930 to 1939, 1940 to 1949, and 1950 to 1989. Descriptive height statistics were estimated by birth years and birth cohorts. Height correlations were examined using sex- and age-specific partial Pearson correlation analyses and meta-regression techniques. RESULTS Across 60 birth years, mean child heights at age 7 increased by 2.9 cm in girls and 3.0 cm in boys, and adult heights increased as well. The proportions of children attaining final height by age 13 remained low across the birth cohorts; nonetheless, there was a significant increase from 0.7% to 1.5% in girls only (P