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Objective: To describe adherence to daily somatropin treatment and impact on height velocity within 1 year of treatment start among patients with pediatric growth hormone deficiency in a real-world US population., Methods: This retrospective cohort study included pediatric patients aged ≥3 years to <16 years with pediatric growth hormone deficiency prescribed somatropin by a pediatric endocrinologist at a US-based center of excellence between January 1, 2015 and December 31, 2020. Patient data were collected using hospital electronic health records linked to a specialty pharmacy patient prescription records. Adherence, evaluated over 12 months, was measured using the proportion of days covered metric and patients were categorized as adherent if their proportion of days covered ≥80%. Height velocity was annualized to compare across adherent and nonadherent patients., Results: One hundred eighty-one patients were identified and included in this study, of which 70.2% were male,73.5% were white, and mean age (standard deviation [SD]) at index was 12.1 (2.8). In the height velocity analysis, 174 patients were included and the mean (SD) annualized change in height was 10.2 (5.7) cm/y in the adherent group (n = 108) and 9.8 (7.6) in the nonadherent group (n = 66). The difference in height velocity between the groups was not statistically significant., Conclusions: Minor improvements in average height velocity were observed in the patient group who were adherent to somatropin therapy, although not statistically significant. Lack of observed significance may be due to small sample sizes, short observation period, a likely heterogenous population in terms of growth hormone prescribing, data bias due to single-center origin, or potential patient misclassification., Competing Interests: Disclosure J.L., J.A., AG, and M.W. are employees of Pfizer Inc and report ownership of Pfizer stock. M.K., S.S., C.P., D.B., J.W., and P.J. are employees of Genesis Research who were paid consultants to Pfizer in connection with this research and development of this manuscript. B.S.M. is a consultant for Ascendis Pharma, BioMarin, Bristol-Myers Squibb, EMD Serono, Endo Pharmaceuticals, Novo Nordisk, Pfizer, Provention Bio, and Tolmar., (Copyright © 2024 Pfizer. Published by Elsevier Inc. All rights reserved.)

Background: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression., Methods: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression., Results: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (β - 7.5 × 10 -6 , CI - 1.2 × 10 -5 , - 3 × 10 -6 , p = 0.001) and incident cases of NS (vs. prevalent) (β - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (β 0.16, CI 0.04, 0.29, p = 0.01) over time., Conclusion: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objectives: This study aimed to analyze the height growth pattern and the incidence of significant growth deceleration in girls with CPP and EFP on GnRHa treatment, and thereby identify relevant predictors of growth deceleration., Methods: The data of 99 girls diagnosed with CPP and 47 girls with EFP were included in this retrospective analysis. The incidence of growth deceleration was calculated in both the first and second years. Multivariate logistic regression analysis was used to identify predictors indicative of growth deceleration., Results: Growth velocity (GV) trajectories showed gradual decreases to the nadir at 18 months of treatment, and then they recovered till the 24th month of treatment, especially in girls with CPP. Nevertheless, the recovery was significantly greater in the CPP group than EFP. In the first year, no significant difference in the incidence of growth deceleration was found between the CPP group and the EFP group [17.35 vs. 25.53 %, p=0.249]; in the second year, the CPP group had a lower incidence than the EFP group [42.86 vs. 76.92 %, p=0.027]. The multivariate logistic regression analysis suggested that bone age (BA) was an independent predictor of growth deceleration (OR=2.264, 95 % CI: 1.268-4.042, p=0.006). The result of ROC curves showed the cut-off value of BA was 11.05 years., Conclusions: GV varies at different periods during GnRHa treatment. GnRHa should be used with more caution for EFP treatment than for CPP. BA can be used to predict the occurrence of growth deceleration during GnRHa treatment., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Purpose of Review: Congenital adrenal hyperplasia (CAH) is a relatively common disorder and one of the most challenging conditions seen by pediatric endocrinologists. Poor linear growth in CAH has been recognized for many years. There are new insights to explain this abnormality and shed light on strategies to promote normal growth., Recent Findings: Published data suggest that the dose of hydrocortisone during two critical periods of rapid growth, namely infancy and at puberty, has a fundamental effect on growth velocity, and by definition adult height. To prevent over-treatment, hydrocortisone dosage should remain within the range of 10-15 mg/m 2 body surface area per day. Precursor steroids such as 17-hydroxy progesterone (17OHP) should not be suppressed to undetectable levels. In fact, 17OHP should always be measurable, as complete suppression suggests over-treatment., Summary: CAH is a challenging disorder. High-quality compliance within the consultation setting, with the patient seeing the same specialist at every visit, will be rewarded by improved long-term growth potential. Quality auxological monitoring can avoid phases of growth suppression. New therapy with CRH receptor antagonists may lead to a more nuanced approach by allowing fine tuning of hydrocortisone replacement without the need to suppress ACTH secretion., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Growth retardation and short final height is a common complication of chronic kidney disease (CKD) beginning in childhood, with profound deleterious effects on quality of life, mental health, and social achievement. Despite optimal treatments of causative factors for growth retardation in children with CKD, more than 50% of patients reach end-stage renal failure with a height >2 SD below the mean, and most do not demonstrate "catch-up" growth after receiving a kidney transplant. Four decades ago, recombinant human growth hormone (rhGH) treatment was introduced after studies showed increased growth velocity and improved height SDS in uremic subjects. Since then, an abundance of published data showed significant improvements in health-related quality of life, and most studies revealed no significant adverse effects. Clinical practice guidelines recommended rhGH treatment in CKD Stages 3-5D and after transplantation. Despite these guidelines, this therapy remained underutilized. Most commonly cited barriers to the implementation of rhGH treatment were the need for daily injections, financial challenges, physicians' unfamiliarity with guidelines, and fear of adverse events., Conclusions: rhGH has been shown to improve growth and final height in short children with CKD, with minimal adverse effects. Despite data of its successful use generated over 3 decades, this treatment is underutilized. More judicious utilization of the treatment should emphasize educating patients, their care givers, and members of the multidisciplinary treating team. Additional studies are needed to assess the longer-term rhGH treatment in larger cohorts of patients, leading to additional supportive data and clearer recommendations., (© 2024 The Author(s). Pediatric Transplantation published by Wiley Periodicals LLC.)

Achondroplasia (ACH) is a rare, autosomal dominant skeletal dysplasia characterized by short stature, characteristic facial configuration, and trident hands. Before vosoritide approval in Japan, patients with ACH could start growth hormone (GH) treatment at age 3 years. However, ACH and its treatment in young Japanese children have not been studied. This retrospective, longitudinal, medical records-based cohort study (before vosoritide approval) summarized symptoms, complications, monitoring, surgery/interventions, and height with/without GH in Japanese patients with ACH <5 years. Complications were observed in 89.2% of all 37 patients; 75.7% required surgery or intervention. All patients were monitored by magnetic resonance imaging; 73.0% had foramen magnum stenosis, while 54.1% had Achondroplasia Foramen Magnum Score 3 or 4. Of 28 GH-treated patients, 22 initiating at age 3 years were generally taller after 12 months versus 9 non-GH-treated patients. Mean annual growth velocity significantly increased from age 2 to 3 versus 3 to 4 years in GH-treated patients (4.37 vs. 7.23 cm/year; p = 0.0014), but not in non-GH-treated patients (4.94 vs. 4.20 cm/year). The mean height at age 4 years with/without GH was 83.6/79.8 cm. These results improve our understanding of young patients with ACH in Japan and confirm that early diagnosis of ACH and monitoring of complications help facilitate appropriate interventions., (© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone., Methods: Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors., Results: Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7 ± 1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p < .01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (β = 0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (β = -0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (β = -0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (β = -0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score., Conclusions: Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population., (© 2024 Wiley Periodicals LLC.)

Objective: To determine the auxological response to recombinant human growth hormone (rhGH) therapy in children with growth hormone deficiency (GHD) presenting at the National Institute of Child Health, Karachi, Pakistan., Study Design:  Observational study. Place and Duration of the Study: Department of Paediatric Endocrinology, National Institute of Child Health, Karachi, Pakistan, from January 2022 to December 2023., Methodology:  All pre-pubertal children with short stature aged 3-12 years diagnosed with GHD and who were prescribed rhGH therapy were included in the study. Children with any other underlying reason for short stature or any other comorbidity were excluded. Patients' demographics and baseline growth parameters were recorded in a pre-designed proforma. Patients were then followed up every three months till one year. Response to rhGH therapy was evaluated through comparison of growth parameters before and after one year of therapy., Results: A total of 90 children including 47 (52.2%) males and 43 (47.8%) females with GHD were enrolled. Mean age of these patients was 7.92 ± 2.647 years. A statistically significant change in height (SD), Weight (SD), and BMI (SD) was observed before and after one year of therapy (p <0.001). Response to therapy in terms of height did not differ significantly with respect to gender (p = 0.955) or stimulated growth hormone levels (p = 0.911). However, response to rhGH therapy was significantly better in terms of increase in height, weight, and BMI in patients presenting earlier i.e. at age ≤8 years., Conclusion: Recombinant human growth hormone therapy was effective in children with short stature to achieve desirable growth. Children diagnosed and treated at a younger age (≤8years) achieve better height outcomes as compared to those presenting late., Key Words:  Short stature, Growth hormone deficiency, Recombinant human growth hormone.

In children and adolescents, impaired growth due to tyrosine kinase inhibitor therapy remains an insufficiently studied adverse effect. This study examines demographic, pharmacological, and genetic factors associated with impaired longitudinal growth in a uniform pediatric cohort treated with imatinib. We analyzed 94 pediatric patients with chronic myeloid leukemia (CML) diagnosed in the chronic phase and treated with imatinib for >12 months who participated in the Germany-wide CML-PAEDII study between February 2006 and February 2021 (clinicaltrials gov. Identifier: NCT00445822). During imatinib treatment, significant height reduction occurred, with medians of -0.35 standard deviation score (SDS) at 12 months and -0.76 SDS at 24 months. Cumulative height SDS change (Δ height SDS) showed a more pronounced effect in prepubertal patients during the first year but were similar between prepubertal and pubertal subgroups by the second year (-0.55 vs. -0.50). From months 12 to 18 on imatinib, only 18% patients achieved individually longitudinal growth adequate to the growth standard (Δ height SDS ≥0). When patients were divided into two subgroups based on median Δ height SDS (classifier Δ height SDS > or ≤-0.37) after 1 year on imatinib therapy, cohort 1 (Δ height SDS ≤-0.37) showed younger age at diagnosis, a higher proportion of prepubertal children, but also better treatment response and higher imatinib serum levels. Exploring the association of growth parameters with pharmacokinetically relevant single nucleotide polymorphisms, known for affecting imatinib response, showed no correlation. This retrospective study provides new insights into imatinib-related growth impairment. We emphasize the importance of optimizing treatment strategies for pediatric patients to realize their maximum growth potential.

Introduction: Growth hormone deficiency occurs when the pituitary gland does not produce enough growth hormone. Norditropin®, a recombinant human growth hormone, and Sogroya®, an albumin-binding growth hormone derivative, are prescribed for patients with growth hormone deficiency. This systematic review assesses the efficacy, safety, and patient satisfaction associated with Norditropin and Sogroya., Methods: We systematically searched PubMed, Web of Science, and Scopus databases to identify eligible comparative studies. All studies published until June 2023 were included in our analysis. Our outcomes for children included height velocity and height velocity standard deviation score. In contrast, adult outcomes included adverse events, insulin-like growth factor 1-standard deviation score (IGF-1 SDS), and the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results are reported as odds ratio (OR) and mean difference (MD) with a 95% confidence interval (95% CI)., Results: Ten studies involving 1058 participants (665 children and 393 adults) were included in the meta-analysis. In children, Norditropin at doses of 0.034 and 0.067 mg/kg/day was compared to Sogroya at doses of 0.04, 0.08, 0.16, and 0.24 mg/kg/week. The results showed that 0.034 mg/kg/day Norditropin had a favorable impact on height velocity (MD -2.01, 95% CI -3.7 to -2.12, p < 0.00001) and height velocity standard deviation score (Mean Difference -3.61, 95% CI -5.06 to -2.16, p < 0.00001) when compared to Sogroya 0.04 mg/kg/day. Other doses showed comparable results. In adults, the only significant side effect noted was rash, which favored Sogroya (OR 0.1, 95% CI 0.04-0.27, p < 0.00001). Additionally, IGF-1 SDS was significantly higher in the Sogroya group than in the Norditropin group (MD 0.25, 95% CI 0.02-0.48, p = 0.03). Furthermore, the overall score of the TSQM-9 questionnaire, which includes three domains: convenience, effectiveness, and satisfaction, was significantly higher in the Sogroya group compared to the Norditropin group (OR 6.36, 95% CI 3.92-8.8, p < 0.00001)., Conclusion: Norditropin and Sogroya showed comparable efficacy and safety profiles, except for the prevalence of rash in the Norditropin group, and Sogroya has higher satisfaction among adults. More high-quality studies with more patients are required to confirm these results., (© 2024. The Author(s).)

Objectives: Clinical benefits of growth hormone (GH) in Prader-Willi syndrome (PWS) are proven and scoliosis is a known association of both PWS and GH therapy. The aims of this study were to assess GH prescribing practices and growth outcomes over time, the prevalence and predictors of scoliosis in GH-treated PWS children, and the near-final height of GH-treated PWS patients., Design and Methods: This is a retrospective, descriptive study evaluating data from all clinic visits of patients aged 0-18 years with PWS, seen through the Children's Hospital at Westmead between March 1992 and May 2022 (n=75)., Results: A total of 64 patients were treated with GH (visits = 1,414). In the recent decade, the diagnosis of PWS and GH commencement were made significantly earlier in life. The prevalence of scoliosis was 41 %, in which age was the only significant predictor for scoliosis (odds ratio 1.19: 95 % CI [1.08-1.31; p=0.001]) adjusted for other predictors. In patients with data available at the age 16 years (23/28 treated with GH), those who were GH treated had significantly higher height SDS vs. nontreated group (SDS -0.67 vs. -2.58; p=0.0001) and lower BMI SDS (1.18 vs. 2.37; p<0.001)., Conclusions: Significant improvements in growth and body composition were seen in the GH-treated group vs. non-treated group of children with PWS. There were no significant modifiable clinical predictors of scoliosis in children with PWS, but our findings confirm the high prevalence of scoliosis in GH-treated children with PWS reinforcing the need for close surveillance., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Short stature with IGF-1 receptor (IGF1R) gene alteration is known as small-for-gestational-age (SGA) short stature with elevated serum IGF1 levels. Its prevalence and clinical characteristics remain unclear. No adapted treatment is available for short stature related to IGF1R gene alteration in Japan, and genetic testing is not yet widely accessible. We investigated short stature with IGF1R gene alterations and analyzed the clinical data of 13 patients using the results of questionnaires issued to the Japanese Society for Pediatric Endocrinology. Four cases were caused by a deletion of chromosome 15q26.3, and eight were caused by heterozygous pathogenic variants in the IGF1R gene. Cases with deletions showed a more severe degree of growth impairment (-4.5 ± 0.43 SD) than those caused by pathological variants (-2.71 ± 0.15 SD) and were accompanied by neurodevelopmental delay. However, cases caused by pathological variants lacked distinctive features. Only three of the 12 cases demonstrated serum IGF1 values exceeding +2 SD, and the other three had values below 0 SD. Four patients did not meet the criteria for SGA at birth. Six patients received GH therapy for SGA short stature and showed improvement in growth rate without any side effects or elevated serum IGF1 levels during treatment. Elevated IGF1 levels (over +2 SD) after GH treatment should be considered a suspicious finding. Owing to the lack of distinctive features, there was a possibility of undiagnosed cases of this condition. Promoting genetic testing and clinical trials on GH administration for this condition is recommended.

Objective: To evaluate the vocal characteristics of children with short stature before and 12 months after growth hormone treatment., Material and Methods: This analytical, observational cohort study included 23 children (age 5-11 years) diagnosed with short stature. Children in the short stature group (SSG) were matched (1:1) for age and sex with children with normal growth (normal stature group; NSG). Participants in the SSG underwent assessments before and 12 months after growth hormone treatment, while those in the NSG underwent the same assessments at baseline and 12 months. The assessments included evaluation of (A) vocal characteristics (history, vocal self-assessment, auditory-perceptual evaluation, and acoustic analysis), (B) anthropometry, (C) bone age, and (D) measurement of insulin-like growth factor-1 (IGF-1) levels., Results: Children in the SSG had more vocal complaints (P = 0.026) than those in the NSG. The groups were similar in terms of vocal self-assessment and auditory-perceptual evaluation (P = nonsignificant). Results of acoustic analysis were also similar for fundamental frequency (F 0) and perturbation measures (P for both = nonsignificant). F 0 and speech frequency decreased significantly at 12 months in both groups. F1 values were higher at 12 months in the NSG, while F2 values were significantly higher in the baseline evaluation in boys in the SSG. Children in the SSG compared with those in the NSG presented a greater increase in height measurements at 12 months, although the anthropometric means were lower in both evaluations (P < 0.001)., Conclusion: Vocal characteristics in children with short stature before and after treatment with growth hormone are comparable to those in children with normal growth., Competing Interests: Conflict of interest None., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is no appropriate tool to predict recombinant human growth hormone (rhGH) response before therapy initiation in short-stature children in late puberty. The current study aimed to explore the associations between magnetic resonance imaging (MRI) stages of the knee growth plates and rhGH response in short-stature children in late puberty., Methods: In this prospective cohort study, short-stature children in late puberty were treated with rhGH and followed up for 6 months. We proposed a novel knee MRI staging system according to the growth plate states of distal femurs or proximal tibias and divided the participants into three groups: unclosed growth plate group, marginally closed growth plate group, and nearly closed growth plate group. The primary outcomes were height gain and growth velocity (GV), which were assessed three months later., Results: Fifty participants were enrolled, including 23 boys and 27 girls. GV and height gain after 6 months of rhGH therapy decreased successively in the three groups with an increased degree of growth plate fusion, especially when grouped by proximal tibias (GV 1-3 mon from 9.38 to 6.08 to 4.56 cm/year, GV 4-6 mon from 6.75 to 4.92 to 3.25 cm/year, and height gain from 4.03 to 2.75 to 1.95 cm, all P < 0.001). Moreover, the MRI stages of growth plates independently served as a significant variable for GV and height gain after therapy, especially when grouped by proximal tibias (all P < 0.01)., Conclusion: The MRI staging method is expected to be an effective tool for predicting rhGH response before therapy initiation in short-stature children in late puberty., (© 2023. The Author(s).)

Objective: There have been rare data on letrozole for height improvement in girls. This study aimed to clarify the efficacy and safety of combination therapy with recombinant human growth hormone (rhGH), GnRHa, and letrozole in improving the height of girls with short stature and advanced bone age., Methods: This was a hospital record-based retrospective study. Follow-up was conducted on girls with short stature who received treatment with rhGH, GnRHa, and letrozole in our hospital. The treatment group included a total of 29 participants. Before treatment, the mean age of the patients was 11.17 years, and the mean treatment duration was 17.31 months. The control group consisted of 29 short-statured girls who received rhGH/GnRHa treatment, with the mean age and treatment duration of 12.43 years and 16.59 months, respectively., Results: The predicted adult heights (PAHs) before and after treatment were 155.38 and 161.32 cm (P < .001). The ΔPAH in the treatment group was 4 cm higher than that in the control group (5.85 vs 1.82 cm, P < .001). Significant differences were noted in the height standard deviation scores of bone age (P < .001) and chronological age (P = .003) before and after treatment. There was an increasing body mass index during therapy (P = .039). The height gain was 8.71 ± 4.46 cm, and the growth rate was 6.78 ± 3.84 cm per year., Conclusion: Combined treatment with GH, GnRHa, and letrozole can enhance the adult height and PAH in short-statured girls, and no significant side effects have been reported., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The aim of this study was to explore the impact of growth hormone (GH) therapy on the onset and progression of puberty in girls with idiopathic short stature., Methods: This study included 541 girls aged between 4.5 and 10.6 years who were receiving GH treatment, monitored over a 22-year follow-up period. Of these, 126 girls have been followed up to the onset of menarche. The participants were divided into two groups: a ISS control group ( n  = 66) and a group receiving daily GH treatment at a dose of 0.15 iu/kg ( n  = 60). We assessed the pubertal development and GH usage of these girls every three months., Results: (1) There was no significant difference in the onset of puberty between the growth hormone (GH) treatment group and the control group; however, the average duration of puberty was longer in the treatment group compared to the control group. (2) During puberty, there were no significant differences in height growth between the treated and untreated groups. (3) The duration of GH treatment showed a significant negative correlation with the age at onset of gonadal development and the age at menarche in females within the treatment group., Conclusion: GH treatment does not seem to accelerate the onset of puberty but may extend its duration, without significantly impacting height growth during puberty. Additionally, longer GH treatment duration is linked to earlier gonadal development and menarche in females.

Introduction: Introduction: early exposure to cadmium toxic metal has been suggested to be associated with reduced infants/children growth; nevertheless, the available evidence is contradictory. Objective: this meta-analysis aimed to examine the association of cadmium exposure through biological samples to growth measurements of infants/children, including body weight, height, body mass index (BMI), BMI-for-age (BMI Z-score), weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z-scores. Methods: a systematic search in PubMed and Scopus was implemented to obtain the related studies. The standardized beta coefficients (β) and 95 % confidence intervals (95 % CI) were used as effect sizes to test the associations using the random effects analysis. Results: a total of 15 studies with 6,181 participants were included in the meta-analysis. In the overall analysis, pooled analysis of available data revealed that cadmium exposure was inversely linked to height (β = -0.06, 95 % CI = -0.12 to -0.01) and WAZ (β = -0.01, 95 % CI = -0.02 to -0.003). These relationships were also supported by prospective cohort studies and urinary cadmium exposure. In the stratified analysis, cadmium exposure was negatively linked to the weight of children in prospective cohort studies, in studies that assessed urinary cadmium exposure. No significant association was detected between cadmium exposure and BMI, BMI Z-score, WHZ, and HAZ in the overall and subgroup analyses. Conclusions: this meta-analysis emphasized the importance of cadmium exposure as a risk factor for growth failure in infants/children.

Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People's Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (P < .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (P < .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months P < .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Context: The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding number of conditions impeding growth are being identified. Among endocrine-related etiologies of short stature amenable to hormonal treatment, defects in the growth hormone (GH)-insulin-like growth factor I axis remain pre-eminent, with a multiplicity of disorders causing decreased secretion or insensitivity to GH action. Sex steroids in puberty increase epiphyseal senescence and eventual growth plate closure. This is mediated mostly via estrogen receptor (ER)α in males and females, effects that can greatly limit time available for growth., Evidence Acquisition: Extensive literature review through PubMed and other search engines., Evidence Synthesis: Therapeutic strategies to be considered in peripubertal and pubertal children with disordered growth are here discussed, including daily and weekly GH, low-dose sex steroids, gonadotropin hormone releasing hormone (GnRH) analogues in combination with GH, aromatase inhibitors (AIs) alone and in combination with GH in boys. When used for at least 2 to 3 years, GnRH analogues combined with GH can result in meaningful increases in height. AIs used with GH permit puberty to progress in boys without hindrance, selectively decreasing estrogen, and resulting in taller height. With more than 20 years of cumulative experience in clinical use of these medications, we discuss the safety profile of these treatments., Conclusion: The approach of growth retardation in the peripubertal and pubertal years must consider the sex steroid milieu and the tempo of bone acceleration. Treatment of affected children in this period must be individualized., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Methylphenidate (MPH), a first-line treatment for attention-deficit hyperactivity disorder (ADHD) management, has been the focus of debate for decades regarding its effect on growth. The aim of this PRISMA meta-analysis was to determine the effect of MPH on height in children/adolescents with ADHD and its predictive factors based on literature reports. Available full-text articles were systematically reviewed to identify clinical studies of pediatric ADHD patients with height Z-score (HZS) data for monotherapy MPH-treated and non-treated groups. We estimated standardized mean differences (SMDs) of HZS or its changes from baseline (ΔHZS) between groups, then identified associated factors through subgroup analyses and meta-regression. For before-after treatment studies, the paired standard errors of ΔHZS were re-estimated to demonstrate in the forest plot. Risk of bias was analyzed using the Newcastle-Ottawa Scale. Among the 29 eligible studies, 26 reported ΔHZS with self-control groups, and ΔHZS or absolute HZS were compared to other external controls in 11 studies. A significant reduction was observed between post-MHP and pre-MPH use, with high heterogeneity (SMD =  - 0.40; 95% confidence interval = [ - 0.54,  - 0.27]; I 2  = 91%). The study region, ADHD subtype, and stimulant-naïve status of patients at baseline may modify the effect on HZS. Because of the high clinical heterogeneity in observational studies, clinicians should consider the negative effect of MPH on height in ADHD patients by determining whether patients fulfill appropriate high-risk criteria. Further well-designed longitudinal studies are required to better quantify this effect, especially with prolonged treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside apart from in two reviews. The resulting rapid advancement of skeletal age causes early completion of growth with shorter adult stature than expected. This appears to be genetic given its occurrence in the present report in two families, one with three brothers, one with two. We also describe potential treatments and found for the youngest that early initiation of standard therapy preserved or reclaimed adult height (AH) potential. The foreshortened AH in this situation involves rapidly advancing puberty resulting from high circulating testosterone levels leading to rapid advance in skeletal age. This was recognized earlier among younger brothers and treatment with gonadotropin-releasing analogues, growth hormone (GH) and/or aromatase inhibitor therapy (AIT) was tried. Two brothers in family A and family B were treated. Case 5 started treatment early enough so his AH was within target height (mid-parental height) range. Cases 2, 3, 4 were tried on GH and/or AIT with outcomes suggesting benefit. The prevalence and mechanism of rapid-tempo puberty requires further study. Furthermore, as illustrated by two of the current cases, this phenomenon may have a heightened prevalence, or at least may occur, in children previously diagnosed with constitutional delay of growth, underscoring the need to be cautious in assurance of a normal AH outcomes in this population, based on data from a single assessment., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Enteral zinc supplementation in preterm infants has been reported to improve short-term weight and height gain. This study aims to evaluate whether early enteral zinc supplementation in preterm infants admitted to the neonatal intensive care unit (NICU) affects their physical measurements at discharge, and to periodically test serum copper levels. Of the 221 patients admitted to the NICU, 102 were in the zinc group and 119 were in the no-zinc group. The zinc group was administered 3 mg/kg/day of zinc. Body weight, height, and head circumference at discharge (or on the expected delivery date) were evaluated, and the factors affecting these parameters were examined. Serum zinc and copper levels were also evaluated on admission and monthly thereafter. Multivariate analysis was performed and showed that the weeks of gestational age and small for gestational age (SGA) status affected the height and weight at discharge. SGA also affected the head circumference. Serum copper levels were within the reference range for all patients at 3 months of age. Enteral zinc supplementation of 3 mg/kg/day in preterm infants did not affect the weight, height, or head circumference at discharge, but was shown to be relatively safe.

Objectives: Somatrogon is a long-acting recombinant human growth hormone used to treat patients with paediatric growth hormone deficiency (pGHD). This global phase 3 study compared the efficacy and safety of once-weekly somatrogon with once-daily somatropin in children with GHD., Methods: Prepubertal patients were randomized 1:1 to once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. The primary endpoint was height velocity (HV) at month 12; secondary endpoints included HV at month 6 and change in height standard deviation score (SDS) at months 6 and 12 and insulin-like growth factor 1 (IGF-1) SDS., Results: This post hoc subgroup analysis focused specifically on Asian children (somatrogon: n=24 and mean age=7.76 years; somatropin: n=21 and mean age=8.10 years) across eight countries. Mean HV at month 12 was 10.95 cm/year (somatrogon) and 9.58 cm/year (somatropin); the treatment difference of 1.38 cm/year favoured somatrogon. The lower bound of the two-sided 95 % CI of the treatment difference (somatrogon-somatropin) was -0.20, similar to the overall study population (-0.24). Compared with the somatropin group, the somatrogon group had numerically higher HV at month 6 (8.31 vs. 11.23 cm/year); a similar trend was observed for height SDS and IGF-1 SDS at months 6 and 12. Safety and tolerability were similar between treatment groups; adverse events occurred in 83 % of somatrogon-treated children and 76 % of somatropin-treated children., Conclusions: This subgroup analysis demonstrated that somatrogon efficacy and safety in Asian children were consistent with the overall study population, where once-weekly somatrogon was non-inferior to once-daily somatropin. Clinicaltrials.gov: NCT02968004., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Introduction: Aromatase inhibitors (AIs) have been used to slow down estrogen-dependent skeletal maturation in pubertal boys with short stature. In the literature, few data evaluate the effectiveness and safety of AIs in boys with growth hormone deficiency (GHD). This study aimed to evaluate the auxologic effects and short-term laboratory profiles of combined AI and rhGH therapy for 1 year in adolescent males with GHD., Subjects and Methods: Male subjects between the ages of 10 and 16 with GHD from two different centers were included in the study. Patients were divided into two groups: (i) those who only used recombinant human growth hormone (rhGH) therapy (Group I; G-I) and (ii) those who also used AI therapy (anastrozole or letrozole) along with rhGH (Group II; G-II)., Results: Forty-one patients (G-I, 46%; G-II, 54%) were included in the study. All the subjects had isolated GHD. At the beginning of the treatment, the chronological ages (CAs) of the patients in the G-I and G-II groups were 11.8 (10.9-13.7) and 12.8 (12.0-14.3) years, respectively. The ratios of bone age (BA)/CA for the two groups were 0.8 (0.8-0.9) and 1.0 (0.9-1.1), respectively (p < 0.001). After the treatment, the height standard deviation (SD) scores and predicted adult height (PAH) significantly increased from baseline in all subjects in the G-I and G-II groups (p < 0.001; p < 0.001, respectively). There was no significant change in the ratio of BA/CA post-therapy in the G-I group (p = 0.1), while there was a significant decrease in the G-II group (p < 0.001). The growth velocities of the patients in the G-I and G-II groups were 9.1 (7.4-10.1) cm/year [1.5 (0.8-5.0) SD score] and 8.7 (7.5-9.9) cm/year [1.1 (0.3-3.1) SD score], respectively (p = 0.6). While post-therapy serum testosterone concentrations were seen to increase in the G-II group, none of the patients exhibited hematocrit above 50 percent, and the fasting glucose concentrations were normal., Conclusions: When used in addition to rhGH therapy in boys with GHD and advanced BA, AIs were observed to slow down the tempo of BA maturation after 1 year, compared to those who received rhGH treatment alone. AI therapy was found to be safe during the 1-year observation period and thus could be considered for preserving growth potential in these patients., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Introduction: Gonadotropin-releasing hormone (GnRH) analogs are the standard treatment for central precocious puberty (CPP). Although there are numerous varieties of GnRH agonists, the effectiveness of 1-monthly compared with 3-monthly Leuprolide acetate is still restricted. The objective of this study was to evaluate the outcomes of CPP treatment with Leuprolide acetate at a 1-monthly dosage of 3.75 mg, in comparison to a dosage of 11.25 mg administered every 3 months., Method: This retrospective cohort study involved 143 girls diagnosed with CPP with 72 of them receiving the monthly treatment regimen and 71 receiving the 3-monthly treatment regimen. Anthropometric measurements were compared at the start and end of the therapy. The rates and level of LH suppression were assessed six months after therapy., Results: The regimen administered every 3 months showed more significant suppression of LH. The 3-monthly group showed lower actual height and degree of bone age advancement at the end of therapy. However, the predicted adult height (PAH) remained comparable in both groups., Conclusion: The 3-monthly treatment showed greater hormonal and growth suppression effects, but there was no significant difference in PAH between the two groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Thaneetrakool, Aroonparkmongkol, Numsriskulrat, Supornsilchai, Wacharasindhu and Srilanchakon.)

Introduction: Short stature in growth hormone deficiency (GHD) can be treated with recombinant human growth hormone (rhGH), which is proven to be both safe and effective. However, a considerable number of patients does not achieve satisfying therapy outcomes., Aim of the Study: To evaluate the predictive effect of height increase in the first year of rhGH treatment on long-term therapy outcomes., Material and Methods: 165 short-stature children (mean age 10.72 ±3.33 years; 63% males), diagnosed with GHD, treated with rhGH for at least one year (mean follow-up 4.32 ±1.80 years), divided into 2 groups according to the change in height standard deviation score (SDS) after the first year of rhGH treatment: good responders (GR) and poor responders (PR). Then, in one-year intervals, patient's chronological age, bone age, height, weight, insulin-like growth factor level, and rhGH dose were all assessed., Results: In the GR group, mean height velocity SDS up to five years of observation was 1.19 ±0.41/year and in the PR group 0.59 ±0.38/year. The differences were statistically significant (p < 0.05)., Conclusions: The primary response to the rhGH treatment in GHD children seems to be a good predictor for long-term therapy outcomes.

Introduction: Preterm neonates often receive a variety of duration of antibiotic exposure during admission. The aim of the study was to evaluate whether neonatal antibiotic exposure is relevant with longitudinal growth problems in preterm-birth children., Methods: This prospective study enrolled 481 infants who were born &lt;32 weeks of gestation, discharged, and longitudinally followed from corrected age (CA) 6-60 months. After excluding 153 infants with blood culture-confirmed bacteremia, necrotizing enterocolitis, severe cerebral palsy, intestinal ostomy, and congenital anomaly, 328 infants were included for analysis. Covariates included perinatal demographics, neonatal morbidities, extrauterine growth restriction, and antibiotic exposure accumulated by term equivalent age. The primary outcome was the anthropometric trajectories in z-score of bodyweight (zBW), body height (zBH), and body mass index (zBMI) from CA 6-60 months., Results: Antibiotic exposure duration was significantly negatively associated with zBW and zBH at CA 6, 12, and 60 months, and zBMI at CA 60 months. Multivariate generalized estimating equation analyses showed antibiotic exposure duration had significantly faltering z-score increment from CA 6 to 60 months in zBW and zBH (adjusted mean [95% CI]; ΔzBW: -0.021 [-0.041 to -0.001], p = 0.042; ΔzBH: -0.019 [-0.035 to -0.002], p = 0.027) after adjustment. Children with neonatal antibiotic exposure duration &gt;15 days were significantly lower in the mean anthropometric zBW, zBH, and zBMI at CA 6, 12, 24, and 60 months compared with children with neonatal antibiotic exposure ≤15 days (all p &lt; 0.01)., Conclusions: Growth increments were negatively associated with antibiotic exposure duration in preterm neonates implicating that antibiotic stewardship and growth follow-up for preterm neonates are thus warranted., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Health related quality of life (HRQoL) is a relevant result when assessing the course of different pathologies and the efficacy of their treatments. HRQoL has been studied previously on adults born small for gestational age (SGA), both in the general population and in patients who had received recombinant human growth hormone (rhGH) treatment, with disparate results. Our study included 50 adults who had received rhGH treatment for the SGA indication in 4 Spanish hospitals. Data have been gathered retrospectively from their clinical records, current weight and height were measured, and patients have been asked to fill out SF-36 and QoLAGHDA quality of life forms, and the Graffar test to evaluate their socio-economical status. Patient's adult height was - 1.2 ± 0.9 SD, lower than their target height of 1 ± 0.8 SD, but gaining 1.7 ± 1 SD from the beginning of the treatment. SF-36 test results showed lower scoring on Mental Health domains than on those related to Physical Health. No correlation was found between HRQoL results and final height, rhGH treatment duration or puberty. Correlation was indeed found between QoLAGHDA and several domains of SF-36, but QoLAGHDA detected fewer patients with low HRQoL than SF-36. Thus, it is concluded that SGA patient's follow-up should include a HRQoL, neuro-cognitive and psychiatric assessment in their transition to adult age. Adult SGA patients without catch up growth have impaired HRQoL, especially in mental health domains., (© 2023. The Author(s).)

Background: Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables., Methods: We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently., Results: The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment., Conclusion: The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yoo, Kim, Jung, Shim, Shim, Kim, Kwak, Kim and Yang.)

Objectives: It is important to understand what variables influence change in predicted adult height (PAH) throughout GnRHa treatment for central precocious puberty (CPP) to individualize treatment decisions and optimize care., Methods: Changes in PAH, chronological age (CA), bone age (BA), BA/CA, and height velocity (HV) were evaluated in girls with CPP throughout treatment with leuprolide acetate (n=77). A second analysis focused on changes in the 3 years preceding the first observed BA of ≥12 years. Relationships were characterized using plot inspection and linear mixed-effects analyses. Association between treatment duration and last assessed PAH was examined using multiple linear regression models., Results: BA/CA and HV showed a nonlinear change during treatment, with the largest changes and improvement in PAH observed in the first 6-18 months. Rate of BA advancement tended to decrease more slowly in girls initiating treatment at a younger BA. On-treatment change in PAH was predicted by concurrent BA/CA change, HV, and BA, as well as CA at treatment initiation. Last assessed PAH was positively associated with longer treatment durations (primary/exploratory models cut-offs of ≥33/≥55 months)., Conclusions: These findings support individualized monitoring during GnRHa treatment. Initial response should be interpreted with caution until 6-18 months after treatment initiation and failure should not be assumed based on continued bone maturation in girls starting therapy at a younger age. Treatment cessation should not be automatically based on a diminishing change in PAH or HV, as ongoing treatment may result in continued increase or maintenance of PAH., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Context: Transgender adolescents can receive gonadotropin-releasing hormone analogues (GnRH) and gender-affirming hormone therapy (GAHT), but little is known about effects on growth and adult height. This is of interest since height differs between sexes and some transgender girls wish to limit their growth., Objective: This work aims to investigate the effects of GnRHa and GAHT on growth, and the efficacy of growth-reductive treatment., Methods: This retrospective cohort study took place at a specialized tertiary gender clinic. A total of 161 transgender girls were treated with GnRHa and estradiol at a regular dose (2 mg) or high growth-reductive doses of estradiol (6 mg) or ethinyl estradiol (EE, 100-200 µg). Main outcome measures included growth, adult height, and the difference from predicted adult height (PAH) and target height., Results: Growth velocity and bone maturation decreased during GnRHa, but increased during GAHT. Adult height after regular-dose treatment was 180.4 ± 5.6 cm, which was 1.5 cm below PAH at the start GnRHa (95% CI, 0.2 cm to 2.7 cm), and close to target height (-1.1 cm; 95% CI, -2.5 cm to 0.3 cm). Compared to regular-dose treatment, high-dose estradiol and EE reduced adult height by 0.9 cm (95% CI, -0.9 cm to 2.8 cm) and 3.0 cm (95% CI, 0.2 cm to 5.8 cm), respectively., Conclusion: Growth decelerated during GnRHa and accelerated during GAHT. After regular-dose treatment, adult height was slightly lower than predicted at start of GnRHa, likely due to systematic overestimation of PAH as described in boys from the general population, but not significantly different from target height. High-dose EE resulted in greater reduction of adult height than high-dose estradiol, but this needs to be weighed against possible adverse effects., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Growth hormone (GH) is used to treat short children born small for gestational age (SGA); however, the effects of treatment on pubertal timing and adult height are rarely studied., Objective: To evaluate adult height and peak height velocity in short GH-treated SGA children., Methods: Prospective longitudinal multicenter study. Participants were short children born SGA treated with GH therapy (n = 102). Adult height was reported in 47 children. A reference cohort of Danish children was used. Main outcome measures were adult height, peak height velocity, age at peak height, and pubertal onset. Pubertal onset was converted to SD score (SDS) using Danish reference data., Results: Gain in height SDS from start of treatment until adult height was significant in both girls (0.94 [0.75; 1.53] SDS, P = .02) and boys (1.57 [1.13; 2.15] SDS, P < .001). No difference in adult height between GH dosage groups was observed. Peak height velocity was lower than a reference cohort for girls (6.5 [5.9; 7.6] cm/year vs 7.9 [7.4; 8.5] cm/year, P < .001) and boys (9.5 [8.4; 10.7] cm/year vs 10.1 [9.7; 10.7] cm/year, P = .002), but no difference in age at peak height velocity was seen. Puberty onset was earlier in SGA boys than a reference cohort (1.06 [-0.03; 1.96] SDS vs 0 SDS, P = .002) but not in girls (0.38 [-0.19; 1.05] SDS vs 0 SDS, P = .18)., Conclusion: GH treatment improved adult height. Peak height velocity was reduced, but age at peak height velocity did not differ compared with the reference cohort. SGA boys had an earlier pubertal onset compared with the reference cohort., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD)., Methods: Total 163 patients aged 2-18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment., Results: The baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment., Conclusion: The 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT01604395., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Context: Rabson-Mendenhall syndrome (RMS) is caused by biallelic pathogenic variants in the insulin receptor gene (INSR) leading to insulin-resistant diabetes, microvascular complications, and growth hormone resistance with short stature. Small, uncontrolled studies suggest that 1-year treatment with recombinant leptin (metreleptin) improves glycemia in RMS., Objective: This study aimed to determine effects of long-term metreleptin in RMS on glycemia, anthropometrics, the growth hormone axis, and kidney function., Methods: We compared RMS patients during nonrandomized open-label treatment with metreleptin (≥ 0.15 mg/kg/day) vs no metreleptin over 90 months (5 subjects in both groups at different times, 4 only in metreleptin group, 2 only in control group). Main outcome measures were A1c; glucose; insulin; 24-hour urine glucose; standard deviation scores (SDS) for height, weight, body mass index (BMI), and insulin-like growth factor 1 (IGF-1); growth hormone; and estimated glomerular filtration rate., Results: Over time, metreleptin-treated subjects maintained 1.8 percentage point lower A1c vs controls (P = 0.007), which remained significant after accounting for changes in insulin doses. Metreleptin-treated subjects had a reduction in BMI SDS, which predicted decreased A1c. Growth hormone increased after metreleptin treatment vs control, with no difference in SDS between groups for IGF-1 or height. Reduced BMI predicted higher growth hormone, while reduced A1c predicted higher IGF-1., Conclusion: Metreleptin alters the natural history of rising A1c in RMS, leading to lower A1c throughout long-term follow-up. Improved glycemia with metreleptin is likely attributable to appetite suppression and lower BMI SDS. Lower BMI after metreleptin may also worsen growth hormone resistance in RMS, resulting in a null effect on IGF-1 and growth despite improved glycemia., (Published by Oxford University Press on behalf of the Endocrine Society 2021.)

Objective: To identify predictors of changes in height, weight, and body mass index (BMI) in children with attention deficit hyperactivity disorder (ADHD) starting central nervous system (CNS) stimulants., Study Design: There were 230 medication-naïve children aged 5-12 years with ADHD who participated in a randomized trial evaluating the impact of CNS stimulants on growth over 30 months. This observational analysis focused on the 141 participants using study medication for 65 or more days in the first 6-months after starting medication. Biometric variables, ADHD, and oppositional defiant disorder symptom scores at medication initiation, and medication use over the study were examined as predictors of changes in standardized (z) height, weight, and BMI., Results: Mean changes in z-BMI, z-weight. and z-height were negative throughout the study. The most consistent predictors of change in z-BMI, z-weight, and z-height were percent days medicated and total medication exposure. Children with lower z-height and z-weight at medication initiation experienced greater z-BMI and z-weight decreases over the first 6 months on medication. Greater appetite suppression during dose optimization predicted greater decreases in z-weight over the entire study and a greater decrease in z-height over the first 6 months on medication. z-weight change correlated with z-height change. Behavioral symptoms did not predict changes in z-BMI, z-weight, or z-height., Conclusions: How much and how often CNS stimulants are used predicts changes in z-BMI, z-weight, and z-height in children. Even smaller and lighter children may be at risk for decreases in z-weight and z-BMI. Parent ratings of appetite during dose titration may serve as feasible indicators of future weight and height change in children using CNS stimulants., Trial Registration: Clinicialtrials.gov: NCT01109849., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Vamorolone is a synthetic steroidal drug with potent anti-inflammatory properties. Initial open-label, multiple ascending dose-finding studies of vamorolone among boys with Duchenne muscular dystrophy (DMD) found significant motor function improvement after 6 months treatment in higher-dose (ie, ≥2.0 mg/kg/d) groups., Objective: To investigate outcomes after 30 months of open-label vamorolone treatment., Design, Setting, and Participants: This nonrandomized controlled trial was conducted by the Cooperative International Neuromuscular Research Group at 11 US and non-US study sites. Participants were 46 boys ages 4.5 to 7.5 years with DMD who completed the 6-month dose-finding study. Data were analyzed from July 2020 through November 2021., Interventions: Participants were enrolled in a 24-month, long-term extension (LTE) study with vamorolone dose escalated to 2.0 or 6.0 mg/kg/d., Main Outcomes and Measures: Change in time-to-stand (TTSTAND) velocity from dose-finding baseline to end of LTE study was the primary outcome. Efficacy assessments included timed function tests, 6-minute walk test, and NorthStar Ambulatory Assessment (NSAA). Participants with DMD treated with glucocorticoids from the Duchenne Natural History Study (DNHS) and NorthStar United Kingdom (NSUK) Network were matched and compared with participants in the LTE study receiving higher doses of vamorolone., Results: Among 46 boys with DMD who completed the dose-finding study, 41 boys (mean [SD] age, 5.33 [0.96] years) completed the LTE study. Among 21 participants treated with higher-dose (ie, ≥2.0 mg/kg/d) vamorolone consistently throughout the 6-month dose-finding and 24-month LTE studies with data available at 30 months, there was a decrease in mean (SD) TTSTAND velocity from baseline to 30 months (0.206 [0.070] rises/s vs 0.189 (0.124) rises/s), which was not a statistically significant change (-0.011 rises/s; CI, -0.068 to 0.046 rises/s). There were no statistically significant differences between participants receiving higher-dose vamorolone and matched participants in the historical control groups receiving glucocorticoid treatment (75 patients in DNHS and 110 patients in NSUK) over a 2-year period in NSAA total score change (0.22 units vs NSUK; 95% CI, -4.48 to 4.04]; P = .92), body mass index z score change (0.002 vs DNHS SD/mo; 95% CI, -0.006 to 0.010; P = .58), or timed function test change. Vamorolone at doses up to 6.0 mg/kg/d was well tolerated, with 5 of 46 participants discontinuing prematurely and for reasons not associated with study drug. Participants in the DNHS treated with glucocorticoids had significant growth delay in comparison with participants treated with vamorolone who had stable height percentiles (0.37 percentile/mo; 95% CI, 0.23 to 0.52 percentile/mo) over time., Conclusions and Relevance: This study found that vamorolone treatment was not associated with a change in TTSTAND velocity from baseline to 30 months among boys with DMD aged 4 to 7 years at enrollment. Vamorolone was associated with maintenance of muscle strength and function up to 30 months, similar to standard of care glucocorticoid therapy, and improved height velocity compared with growth deceleration associated with glucocorticoid treatment, suggesting that vamorolone may be an attractive candidate for treatment of DMD., Trial Registration: ClinicalTrials.gov Identifier: NCT03038399.

Objectives: Growth impairment is a common manifestation in Noonan syndrome (NS). Recombinant human GH (rhGH) treatment has been shown to increase growth and adult height (AH) in a few studies. We aimed to evaluate the growth trajectory towards the AH, and the effects of rhGH treatment in a large cohort of NS children., Methods: Retrospective, multicenter, cohort study including subjects with genetic diagnosis of NS. A total of 228 NS patients, 154 with PTPN11 mutations, 94 who reached AH, were recruited. Auxological data were collected at 2, 5, and 10 years, at pubertal onset, at AH. Sixty-eight NS subjects affected with GH deficiency (GHD) were treated with rhGH at a mean dose of 0.24 mg/kg per week until AH achievement., Results: ANOVA analysis showed a significant difference between birth length and height standard deviation scores (HSDS) at the different key ages ( p<0.001 ), while no significant differences were found between HSDS measurements at 2, 5, and 10 years, at pubertal onset, and at AH. HSDS increased from -3.10 ± 0.84 to -2.31 ± 0.99 during rhGH treatment, with a total height gain of 0.79 ± 0.74, and no significant difference between untreated and treated NS at AH., Conclusions: rhGH treatment at the standard dose used for children with GH idiopathic deficiency is effective in improving growth and AH in NS with GHD. Further studies are needed to assess genotype-specific response to rhGH treatment in the different pathogenic variants of PTPN11 gene and in the less common genotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Libraro, D’Ascanio, Cappa, Chiarito, Digilio, Einaudi, Grandone, Maghnie, Mazzanti, Mussa, Patti, Scarano, Spinuzza, Vannelli, Wasniewska, Ferrero and Faienza.)

Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. If rhGH-treated children with growth hormone deficiency or those who were born small-for-gestational age are still short at pubertal onset, co-treatment with a GnRHa for 2-3 years increases AH. A similar effect was seen by adding rhGH to GnRHa treatment of children with central precocious puberty with a poor AH prediction and by adding rhGH plus GnRHa to children with congenital adrenal hyperplasia with a poor predicted adult height on conventional treatment with gluco- and mineralocorticoids. In girls with idiopathic short stature and relatively early puberty, rhGH plus GnRHa increases AH. Administration of letrozole to boys with constitutional delay of growth puberty may increase AH, and rhGH plus anastrozole may increase AH in boys with growth hormone deficiency or idiopathic short stature, but the lack of data on attained AH and potential selective loss-of-follow-up in several studies precludes firm conclusions. GnRHas appear to have a good overall safety profile, while for aromatase inhibitors conflicting data have been reported., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wit.)

Idiopathic short stature (ISS) is a term used to describe a selection of short children for whom no precise aetiology has been identified. Molecular investigations have made notable discoveries in children with ISS, thus removing them from this category. However, many, if not the majority of children referred with short stature, are designated ISS. Our interest in defects of GH action, i.e. GH resistance, has led to a study of children with mild GH resistance, who we believe can be mis-categorised as ISS leading to potential inappropriate management. Approval of ISS by the FDA for hGH therapy has resulted in many short children receiving this treatment. The results are extremely variable. It is therefore important to correctly assess and investigate all ISS subjects in order to identify those with mild but unequivocal GH resistance, as in cases of PAPP-A2 deficiency. The correct identification of GH resistance defects will direct therapy towards rhIGF-I rather than rhGH. This example illustrates the importance of recognition of GH resistance among the very large number patients referred with short stature who are labelled as 'ISS'., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Savage and Storr.)

Background: Short stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS., Methods: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450-0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450-0.050 mg] /kg/day)., Results: The change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (- 1.02) satisfied the non-inferiority margin (- 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups., Conclusions: This study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future., Trial Registration: The study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013)., (© 2021. The Author(s).)

Serum insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) levels can be used to monitor the safety of recombinant human growth hormone (rhGH) therapy. In this study, we evaluated the changes in serum IGF-I and IGFBP-3 levels during rhGH therapy as a marker of height outcome in prepubertal children. Totally, 705 prepubertal children with short stature were enrolled from the LG Growth Study Database. Data for three groups of subjects were obtained as follows: Idiopathic GH deficiency (IGHD; n = 486); idiopathic short stature (n = 66); small for gestational age (n = 153). Serum IGF-I and IGFBP-3 levels at the baseline and after the 1st and 2nd year of rhGH therapy, as well as the Δheight standard deviation score (SDS), were obtained. Δheight SDS after the 1st and 2nd year of rhGH therapy had notably increased compared to that at the baseline for all three groups. IGF-I and IGFBP-3 levels in all three groups were significantly increased compared to those at the baseline (p <0.001). Δheight SDS was positively correlated with ΔIGF-1 SDS after the 1st year of therapy, ΔIGFBP-3 SDS after the 2nd year of therapy in the IGHD group, and ΔIGF-I SDS and ΔIGFBP-3 SDS after the 2nd year of therapy (p < 0.05), regardless of whether the height at the baseline was a covariate. The increase in IGF-I and IGFBP-3 levels during rhGH therapy was related to the growth response in children with IGHD. Therefore, it may be valuable to measure the change in serum IGF-I and IGFBP-3 levels, especially the latter, during rhGH treatment to predict the growth response upon long-term treatment., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To investigate predictors of testicular response and non-reproductive outcomes (height, body proportions) after gonadotropin-induced puberty in congenital hypogonadotropic hypogonadism (CHH)., Design: A retrospective analysis of the puberty induction in CHH male patients, undergoing an off-label administration of combined gonadotropin (FSH and hCG)., Methods: Clinical and hormonal evaluations before and during gonadotropin stimulation in 19 CHH patients genotyped by Targeted Next Generation Sequencing for CHH genes; 16 patients underwent also semen analysis after gonadotropins., Results: A lesser increase in testicular volume after 24 months of induction was significantly associated with: (I) cryptorchidism; (II) a positive genetic background; (III) a complete form of CHH. We found no significant correlation with the cumulative dose of hCG administered in 24 months. We found no association with the results of semen analyses, probably due to the low numerosity. Measures of body disproportion (eunuchoid habitus and difference between adult and target height: deltaSDSth), were significantly related to the: (I) age at the beginning of puberty induction; (II) duration of growth during the induction; (III) initial bone age. The duration of growth during induction was associated with previous testosterone priming and to partial forms of CHH., Conclusions: This study shows that a strong genetic background and cryptorchidism, as indicators of a complete GnRH deficiency since intrauterine life, are negative predictors of testicular response to gonadotropin stimulation in CHH. Body disproportion is associated with a delay in treatment and duration of growth during the induction, which is apparently inversely related to previous androgenization., (© 2021. The Author(s).)

Objective: This study aimed to determine the most appropriate age for height control treatment in patients with Marfan syndrome (MFS)., Materials and Methods: This 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., Results: Seventeen 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., Conclusion: Initiating height control treatment before the age of 10.5 years is effective in female patients with MFS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Lee, Kim, Cho, Jin and Choi.)

Failure to thrive (FTT) impairs the expected normal physical growth of children. This study aimed to evaluate the effects of cyproheptadine hydrochloride on growth parameters in prepubertal children with FTT. The medical records of prepubertal children who were newly diagnosed with FTT at China Medical University Hospital between 2007 and 2016 were retrospectively examined. The patients were divided into two groups depending on whether they had (T-group) or had not (NT-group) received cyproheptadine hydrochloride (0.3 mg/kg daily) for at least 14 days. The mean length of the treatment period was 97.22 days (range: 14-532 days). Weight, height, and body mass index were adjusted for age using the median values in the growth charts for Taiwanese boys and girls as the reference. A total of 788 patients aged 3-11 years were enrolled, 50 in the T-group and 738 in the NT-group. No statistically significant difference in the median age-adjusted weight value was noted between the T-group and NT-group during the follow up period. In the T-group, age-adjusted weight and body mass index were inversely associated with age (P <0.001, P <0.001) and positively associated with medication duration (P = 0.026, P = 0.04). Our findings underscore the positive association between cyproheptadine hydrochloride treatment and weight gain among prepubertal children. Further prospective clinical studies with a. longer and consistent treatment course is warranted., Competing Interests: The authors have declared that no competing interests exist.

Aim: To determine the effects of drug therapy on the physical growth of school-age children and adolescents with attention-deficit/hyperactivity disorder (ADHD)., Method: The medical records of 86 participants (average age: 8.9 ± 2.2 years) with ADHD prescribed methylphenidate (MPH) or atomoxetine (ATX) for ≥24 weeks from the Children's Hospital of Chongqing Medical University were analysed., Results: The Z-scores of height, weight and body mass index (BMI) of children with ADHD decreased significantly over the first six months of MPH treatment (P < 0.001). The slopes of the fitting lines after the first six months of MPH (-0.18, -0.58 and -0.69, respectively) returned over the entire treatment (the slopes changed to -0.027, -0.26 and -0.20, respectively). For ATX, the Z-scores of height of children decreased significantly over the first six months (P < 0.001), but the Z-scores of weight and BMI did not (P > 0.05). The slopes of the fitting lines after the first six months of ATX (-0.058, -0.032 and 0.0094, respectively) changed over the entire treatment (slopes were 0.16, 0.52 and 0.26, respectively). Children taking MPH were more likely to report decreased appetite (P < 0.05). The weight and BMI of the children receiving MPH were significantly correlated with decreased appetite (P < 0.01)., Conclusion: The physical growth indexes (PGIs) of school-age children and adolescents with ADHD were negatively affected while taking MPH, and these effects were gradually mitigated with continued treatment. ATX hardly had negative effects on weight and BMI. Neither MPH nor ATX had a significant negative effect on the height of children in long-term ADHD treatment. It is necessary for clinicians to consider children's diet during treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19 th century. Its non-acquired variant (naGHD) is, at childhood onset, a rare syndrome of multiple etiologies, predominantly characterized by severe and permanent growth failure culminating in short stature. It is still difficult to diagnose GHD and, in particular, to ascertain impaired GH secretion in comparison to levels in normally-growing children. The debate on what constitutes an optimal diagnostic process continues. Treatment of the GH deficit via replacement with cadaveric pituitary human GH (pit-hGH) had first been demonstrated in 1958, and opened an era of therapeutic possibilities, albeit for a limited number of patients. In 1985, the era of recombinant hGH (r-hGH) began: unlimited supply meant that substantial long-term experience could be gained, with greater focus on efficacy, safety and costs. However, even today, the results of current treatment regimes indicate that there is still a substantial fraction of children who do not achieve adult height within the normal range. Renewed evaluation of height outcomes in childhood-onset naGHD is required for a better understanding of the underlying causes, whereby the role of various factors - diagnostics, treatment modalities, mode of treatment evaluation - during the important phases of child growth - infancy, childhood and puberty - are further explored., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ranke.)

Oral nutritional supplements (ONS) are used to promote catch-up growth in children with undernutrition. We conducted a systematic review and meta-analysis to summarize the evidence of ONS intervention effects on growth for 9-month- to 12-year-old children who were undernourished or at nutritional risk. Eleven randomized controlled trials met the inclusion criteria; trials compared changes in anthropometric measures in children using ONS or ONS + DC (dietary counselling) to measures for those following usual diet or placebo or DC alone. The RCTs included 2287 children without chronic diseases (mean age 5.87 years [SD, 1.35]; 56% boys). At follow-up time points up to 6 months, results showed that children in the ONS intervention group had greater gains in weight (0.423 kg, [95% confidence interval 0.234, 0.613], p < 0.001) and height (0.417 cm [0.059, 0.776], p = 0.022) versus control; greater gains in weight (0.089 kg [0.049, 0.130], p < 0.001) were evident as early as 7-10 days. Longitudinal analyses with repeated measures at 30, 60, and 90 days showed greater gains in weight parameters from 30 days onwards ( p < 0.001), a trend towards greater height gains at 90 days ( p = 0.056), and significantly greater gains in height-for-age percentiles and Z-scores at 30 and 90 days, respectively ( p < 0.05). Similar results were found in subgroup analyses of studies comparing ONS + DC to DC alone. For children with undernutrition, particularly those who were mildly and moderately undernourished, usage of ONS in a nutritional intervention resulted in significantly better growth outcomes when compared to control treatments (usual diet, placebo or DC alone).

This study aimed to investigate the relationships between genetic polymorphisms of leptin/receptor genes and clinical/biochemical characteristics in children with growth hormone deficiency (GHD). Ninety-three GHD children and 69 age-matched normal controls were enrolled. Anthropometric measurements, bone age, and laboratory test results were obtained. Polymorphisms in the LEP gene promoter locus (LEP-2548, rs7799039) and LEPR genes (K109R, rs1137100 and Q223R, rs1137101) were analyzed using PCR-RFLP. The serum leptin levels were measured using an ELISA kit. The median height and BMI z-scores of all GHD subjects were -2.20 and -0.26, respectively, and those of normal controls were -0.30 and -0.13, respectively. The serum leptin levels were similar between GHD subjects and normal controls (p = 0.537), but those were different between the complete GHD (6.97 ng/mL) and partial GHD (4.22 ng/mL) groups (p = 0.047). There were no differences in the genotypic distributions of LEP-2548, LEPR K109R, and Q223R between GHD subjects and normal controls. However, GHD subjects with the G allele at LEP-2548 showed higher IGF-1 (p = 0.047) and IGFBP-3 SDSs (p = 0.027) than GHD subjects with the A allele. GHD subjects with the G allele at LEPR Q223R showed lower stimulated GH levels (p = 0.023) and greater height gain after 1 year of GH treatment (p = 0.034) than GHD subjects with the A allele. In conclusion, leptin/leptin receptor genes are suggested to have the role of growth-related factors, which can affect various growth responses in children who share the same disease entity.