Growth Hormone Treatment In Children Research Articles

Potential for Optimization of Growth Hormone Treatment in Children with Growth Hormone Deficiency (GHD), Small for Gestational Age (SGA), and Turner Syndrome (TS) in Germany - Data from the PATRO® Children Study.

Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real world treatment. German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 - 2018 to determine specific parameters for GH treatment optimization. All patient groups started GH treatment at a relatively high chronological age (2007 - 2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016 to 2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups female patients were underrepresented compared to male patients (GHD 32.3 %, SGA 43.6 %) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients GH therapy was started below the registered dose recommendation (0.030 mg/kg/day and 0.0337 mg/kg/day, respectively). In the first year of treatment the mean GH dose was increased moderately (GHD: 0.0307, SGA: 0.0357, TS: 0.0408 mg/kg/day). There was no significant change of GH dosing over time from 2007 - 2018. The IoR was comparable between time-groups for all three diagnoses. This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at start of treatment. This is in accordance with important parameters used in prediction models.

Adherence to Growth Hormone Treatment in Children During COVID-19 Pandemic

Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the COVID-19 pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. This was a multicenter survey study that was sent to pediatric endocrinologists in pandemic period (June 2021-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, and missed dose data and the causes in the recent year (after the onset of the pandemic) were queried. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% nonadherence). The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 mcg/kg, the annual growth rate was 1.15 SDS (min -2.74, max 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for nonadherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Nonadherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as nonadherence rate increased. During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

Long-term risk of neoplastic events after childhood growth hormone treatment: a population-based cohort study in Sweden.

Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited. A nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020. 53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26). No association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.

Growth hormone treatment in children with short stature: impact of the diagnosis on parents.

This prospective multicenter study aimed (1) to examine changes in parent-reported health-related quality of life (HRQOL) of children with short stature and the effects of the children's condition on parents themselves within the first year of human growth hormone (hGH) treatment and (2) to predict effects on parents based on main and interaction effects of children's HRQOL and increase in height. A total of 110 parents of children aged 4-18 years, diagnosed with idiopathic growth hormone deficiency, small for gestational age, or idiopathic short stature, were recruited from 11 participating German pediatric endocrinologists and asked to fill out the short stature-specific Quality of Life in Short Stature Youth (QoLISSY) Questionnaire before hGH treatment was initiated and one year later. Negative effects of the children's short stature on the parents decrease over time, independent of diagnosis and treatment status. Furthermore, treatment status and height increase moderated the links between children's improved HRQOL as perceived by their parents and decreased caregiving burden. Based on the children's improved HRQOL and the parent's decrease in caregiving burden, patient-reported outcomes that consider parental and child's perspectives should be considered when deciding on hGH treatment for children.

Measured resting energy expenditure by indirect calorimetry and energy intake in long-term growth hormone treated children with PWS.

Severe obesity can develop in children with PWS when food intake is not controlled. Maintenance of body weight requires an energy balance, of which energy intake and energy expenditure are important components. Previous studies described a decreased resting energy expenditure (REE) in growth hormone (GH)-untreated children with PWS. In short-term studies, no difference in REE was found between GH-treated and untreated children with PWS. However, there are limited data on REE in children with PWS who were GH-treated for a long period. This study describes measured REE (mREE), energy intake and body composition during long-term GH-treatment in children with PWS. Patients were treated with 1.0 mg GH/m2/day (~0.035mg/kg/day). REE was determined by indirect calorimetry; dietary energy intake was calculated using a 3-day dietary record. Body composition by Dual energy X-ray absorptiometry (DXA) scans. We included 52 GH-treated children with PWS with mean (SD) age of 8.53 (4.35) years and median (IQR) GH-treatment duration of 7 (4-11) years. mREE increased with age, but was not associated with GH-treatment duration. A higher LBM was associated with higher mREE. Mean energy intake was significantly lower compared to daily energy requirements (DER) for age- and sex-matched healthy children (p<0.001), ranging from 23-36% less intake in children aged 3.5-12 years to 49% less intake in children aged 12-18 years. Fifty percent of children had a normal REE, 17.3 % a decreased REE and 32.7% an elevated REE, according to predicted REE based on measured REE in a large group of healthy children. In children with PWS, mREE increases with age. GH-treatment duration is not associated, whereas LBM is an important determinant of mREE. Children with PWS have a low to very low energy intake compared to DER for age- and sex-matched children, with a declining intake when becoming older.

Clinical Characteristics of Pathogenic ACAN Variants and 3-Year Response to Growth Hormone Treatment: Real-World Data

Introduction: Heterozygous variants in the ACAN gene may underlie disproportionate short stature with characteristically accelerated bone age (BA) maturation and/or early-onset osteoarthritis (OA). Methods: The objective of this study was to describe phenotype, analyze genotype-phenotype correlations, and assess the response of growth hormone (GH) treatment in children with a heterozygous ACAN variant. Thirty-six subjects (23 boys, 13 girls) with ACAN deficiency and treated for ≥1 year with GH were identified in the Dutch National Registry of GH treatment in children. Results: We identified 25 different heterozygous ACAN variants in 36 subjects. Median (interquartile range) height SDS at start of GH was −2.6 SDS (−3.2 to −2.2). Characteristic features such as disproportion, advanced BA, early-onset OA, and dysmorphic features like midface hypoplasia and brachydactyly were present in the majority of children, but in ∼20%, no specific features were reported. Subjects with a truncating ACAN variant had a shorter height SDS compared to subjects with a non-truncating variant (−2.8 SDS and −2.1 SDS, respectively, p = 0.002). After 3 years of GH, height gain SDS in prepubertal children was 1.0 SDS (0.9–1.4). In pubertal children, height SDS remained relatively stable. Conclusion: The phenotype of subjects with pathogenic heterozygous ACAN variants is highly variable, and genetic testing for ACAN deficiency should be considered in any child with significant short stature, even in the absence of disproportion, specific dysmorphic features, or BA advancement. Furthermore, children with ACAN deficiency may benefit from GH with a modest but significant response, which is sustained during 3 years of treatment.

Growth hormone treatment for children with mucopolysaccharidosis I or II

Growth hormone treatment for children with mucopolysaccharidosis I or II

The influence of pituitary volume on the growth response in growth hormone-treated children with growth hormone deficiency or idiopathic short stature.

Magnetic resonance imaging (MRI) can be used for assessing the morphology of the pituitary gland in children with short stature. The purposes of this study were: (1) to determine if pituitary volume (PV) can distinguish patients with growth hormone (GH) deficiency from those with idiopathic short stature (ISS), (2) to validate an association between PV and severity of GH deficiency, and (3) to compare PV between good and poor response groups in children with GH deficiency or ISS after 1 year of treatment. Data were collected from the medical records of 152 children with GH deficiency or ISS who underwent GH stimulation test, sella MRI, and GH treatment for at least 1 year. Estimated PVs were calculated using the formula of an ellipsoid. We compared the PVs in patients with GH deficiency with those of patients with ISS. In addition, we assessed the association between PV and severity of GH deficiency, and we assessed growth response after treatment. No difference was observed in PV between patients with GH deficiency and those with ISS. The severity of the GH deficiency seemed to be associated with PV (P=0.082), and the height of the pituitary gland was associated with severity of GH deficiency (P<0.005). The PV in the good response group was less than that of the poor response group in patients with GH deficiency (P<0.005), and PV showed no association with responsiveness to GH treatment in patients with ISS (P=0.073). The measurement of PV cannot be used for differential diagnosis between GH deficiency and ISS. In patients with GH deficiency, PV tended to be smaller as the severity of GH deficiency increased, but the difference was not significant. PV may be a good response predictor for GH treatment. Further studies, including a radiomics-based approach, will be helpful in elucidating the clinical implications of pituitary morphology in patients with short stature.

OR21-01 Pre-treatment Blood Transcriptome Predicts First-year Growth And IGF-I Response To Somapacitan Treatment In Children With GH Deficiency

Abstract Disclosure: T. Garner: Grant Recipient; Self; Novo Nordisk. P.E. Clayton: Grant Recipient; Self; Novo Nordisk. M. Hojby: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. P. Murray: Grant Recipient; Self; Novo Nordisk. A. Stevens: Grant Recipient; Self; Novo Nordisk. Background: Growth hormone (GH) replacement therapy often requires daily subcutaneous injections that can be burdensome for patients and their caregivers. Somapacitan is a long-acting, once-weekly GH derivative in development for treating GH deficiency (GHD) in children. Somapacitan reduces treatment burden and shows a similar efficacy and safety profile as daily GH in children with GHD. Here, we investigate the prediction of first-year growth and insulin-like growth factor-I (IGF-I) response based on baseline blood transcriptome in children with GHD treated with somapacitan or daily GH. Methods: 200 treatment-naïve prepubertal children with GHD were enrolled into REAL4, a randomised, multinational, open-labelled, and active-controlled phase 3 trial. 128 consented to a baseline blood transcriptome profile. Children were treated with once-weekly somapacitan (n=81) or daily GH (n=47) for 52 weeks and categorised based on treatment response: the upper quartile of height velocity (HV; cm/year) was defined as good responders, and the lower quartile as poor responders. We split the somapacitan group into training (70%) and testing (30%) sets for prediction validation of HV and the GH response marker: ΔIGF-I standard deviation score (SDS). Gene expression was assessed between the target quartile and the remaining quartiles for both HV and ΔIGF-I SDS to identify the top 100 differentially expressed genes by adjusted p-value. Classes were balanced using a synthetic minority oversampling technique and Boruta, a feature selection algorithm, was used to refine gene lists. We performed random forest and calculated “out of box” (OOB) area under the curve (AUC) and OOB error rate (ER), measures of predictive accuracy and robustness, respectively. Results: HV prediction from the transcriptome was excellent for both treatments (AUC range: 0.95-0.99). It was more robust for identifying good responders (ER: 7.0-7.5%) than poor responders (ER: 13.2-17.5%). Genes previously identified as predictive of growth response for daily GH (Stevens et al., 2021. The Pharmacogenomics J., 21:594-607) were demonstrated to have high predictive value for once-weekly somapacitan and daily GH treatment in this study (AUC range: 0.84-0.97, ER &amp;lt;22%). Using the somapacitan group for validation, HV prediction (AUC range: 0.78-0.81) was stronger than ΔIGF-I SDS prediction (AUC range: 0.63-0.72). Conclusions: We demonstrate pre-treatment blood transcriptome predicts first-year growth response for somapacitan. This represents an independent validation of earlier observations and shows that genes predictive of growth response for daily GH treatment in children with GHD are also predictive for once-weekly somapacitan. Further, we demonstrate that the pre-treatment blood transcriptome predicts growth response better than it predicts IGF-I SDS response. Presentation: Saturday, June 17, 2023

FRI456 Endocrine and Non-Endocrine Causes of Fatigue in Adults With Turner Syndrome: Cohort Study and Review of the Literature

Abstract Disclosure: A.G. Rosenberg: None. V.D. Dingemans: None. A.G. Bos-Roubos: None. S. Luijks: None. A.B. Dessens: None. R. Dykgraaf: None. J.W. Roos-Hesselink: None. E.F. van Rossum: None. A.J. van der Lely: None. L.C. de Graaff: None. Background: Turner syndrome (TS) is a rare genetic developmental disorder characterized by gonadal dysfunction, short stature and heart defects, among others. Women with TS often suffer from severe fatigue, for which they are typically referred to endocrinologists. The diagnostic work-up is generally time-consuming and invasive, but it rarely solves the problem. To prevent the personal and financial burden of unnecessary diagnostic procedures, it is crucial to understand fatigue in TS. Therefore, in this study, we explored the association between fatigue and endocrine and non-endocrine comorbidities in a - for rare disorders - large group of TS women. Design: Cross-sectional study. Methods: 170 genetically confirmed TS women who attended the TS reference center underwent a systematic health screening, including a structured interview, complete physical examination, biochemical measurements, perceived stress and fatigue questionnaires and additional tests when indicated. Results: Median age was 32.6 years (IQR 23.9 - 41.4 years) and median BMI was 25.4 kg/m2 (IQR 22.6 - 28.5 kg/m2). One in three TS women experienced severe fatigue. Liver enzyme disturbances and body mass index were significantly associated with higher fatigue scores, while childhood growth hormone treatment was associated with lower fatigue scores. Perceived stress was highly correlated with fatigue (ρ = 0.71; P &amp;lt; 0.001). Conclusions: There was no association between fatigue and most endocrine and non-endocrine disorders, which implies that fatigue is only partly explained by somatic disorders. The high correlation between perceived stress and fatigue suggests that TS-specific neuropsychological processes may play an important role in the etiology of fatigue in TS women. We provide a practical algorithm for the endocrine, non-endocrine and psychological approach to fatigue in TS women. Presentation Date: Friday, June 16, 2023

Metabolic and growth outcome of two-years growth hormone treatment in children born small for gestational age (SGA): A retrospective study

Metabolic and growth outcome of two-years growth hormone treatment in children born small for gestational age (SGA): A retrospective study

Childhood growth hormone treatment and metabolic and cardiovascular risk in adults born small for gestational age after growth hormone cessation in the Netherlands: a 12-year follow-up study

Childhood growth hormone treatment and metabolic and cardiovascular risk in adults born small for gestational age after growth hormone cessation in the Netherlands: a 12-year follow-up study

A Personalized Approach to Determining the Caloric Needs of Children with Prader-Willi Syndrome Treated with Growth Hormone.

Prader-Willi Syndrome (PWS) is the most frequent cause of genetic obesity. Early reports indicate that children with PWS require 20-40% fewer calories than healthy children to maintain adequate growth. Growth hormone treatment for children with PWS, approved in 2000, affects the body composition and probably affects energy requirements. This retrospective cross-sectional study analyzed the caloric intake in children with PWS aged from 6 months to 12 years old who underwent growth hormone treatment, comparing the patients' caloric intake calculated from parent-recorded dietary intake versus the recommended caloric intake for healthy children, taking into account the age, sex, height, weight, and physical activity. We analyzed the data from 25 patients (13 (52%) boys; mean age, 6.72 ± 2.81 y; median age at starting growth hormone treatment, 1.4 y (IQR: 0.78-2.29); 17 (68%) normal weight and 8 (32%) overweight or obese). The mean daily energy intake was 1208 ± 186 kcal/d, representing 96.83% ± 18.66 of the recommended caloric intake for healthy children. The caloric intake in children with PWS treated with growth hormone was very similar to that recommended for healthy children; thus, we should rethink the dietary recommendations for these children.

Comparison of growth response and adverse reaction according to growth hormone dosing strategy for children with short stature: LG Growth Study

ObjectiveGrowth hormone (GH) dosage in children is conventionally determined either by body weight (BW) or body surface area (BSA). However, there is no consensus on the calculation method for proper GH treatment dose. We aimed to compare growth response and adverse reactions between BW- and BSA-based GH treatment doses for children with short statures. DesignData from 2284 GH-treated children were analyzed. Distributions of BW- and BSA-based GH treatment doses and their association with growth response parameters, including changes in height, height standard deviation score (SDS), body mass index (BMI), and safety parameters, such as changes in insulin-like growth factor (IGF)-I SDS and adverse events, were investigated. ResultsThe mean BW-based doses were close to the recommended dose's upper limit in participants with GH deficiency and idiopathic short stature, while they were below the recommended dose in patients with Turner syndrome (TS). As age and BW increased, BW-based dose decreased, whereas BSA-based dose increased. Gain in height SDS was positively associated with BW-based dose in the TS group and negatively associated with BW in all groups. Despite having a lower BW-based dose, the overweight/obese groups had a higher BSA-based dose and higher frequencies of children with high IGF-I and adverse events than those of the normal-BMI group. ConclusionsIn children of older age or with high BW, BW-based doses can be overdosed in terms of BSA. and BW-based dose positively correlated with height gain only in the TS group. BSA-based doses represent an alternative dosing strategy in children who are overweight/obese.

International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood.

This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.

Very young children with Prader-Willi syndrome are refractory to growth hormone-associated decreases in free thyroxine levels.

The earlier initiation of growth hormone (GH) treatment for patients with Prader-Willi syndrome (PWS) who are younger than 2 years has become more prevalent. Because free thyroxine (FT4) levels are low during this period, GH may induce further reductions; however, limited information is currently available on this issue. Therefore, we herein performed age-dependent and time-course analyses of thyroid hormone levels in GH-treated PWS children. This retrospective analysis included genetically diagnosed PWS patients (N = 37, median age of 26 months). An age-dependent analysis was performed by subdividing subjects based on age [a younger group aged between 1 and 24 months (N = 16) and an older group between 25 and 84 months (N = 21)] and was followed by a multiple regression analysis with adjustments for sex and the cumulative GH dose per bodyweight. A time-course analysis of subjects who had not received levothyroxine during the first 18 months of GH treatment (N = 28) was conducted. A one-month treatment with GH decreased FT4 levels in the older group, but not in the younger group, and this was associated with increases in thyroid-stimulating hormone levels. A positive correlation was noted between age and decreases in FT4 levels independent of the cumulative GH dose per bodyweight. The time-course analysis revealed no changes in FT4 levels in the younger group, while transient decreases were observed in the older group. In conclusion, GH treatment causes age-dependent changes in FT4 levels. This result will help clinicians establish a therapeutic strategy to decide the necessity of levothyroxine supplementation in GH-treated children with PWS.

Reductions in estimated glomerular filtration rate during puberty in GH-treated children born small for gestational age are associated with prematurity and low birth weight, not the dosage of GH treatment.

GH treatment has been widely utilized for short-statured children born small for gestational age (SGA). Although SGA children are at a higher risk of renal dysfunction, the effect of GH treatment on renal function is still unclear. We have previously shown that GH treatment is not associated with renal dysfunction during the prepubertal period; however, its effect during the pubertal period has not been investigated. Accordingly, we herein retrospectively investigated creatinine-based estimated glomerular filtration rates (eGFR) in 26 short-statured children born SGA during puberty, defined as the period between the onset of puberty and cessation of GH treatment, and their association with parameters at birth and GH treatment. We found that eGFR did not decrease during the pubertal period; however, gestational week and birth weight were negatively and significantly correlated with percentage decrease in eGFR during the pubertal period. The percentage decrease in eGFR did not correlate with changes in the insulin-like growth factor-1 standard deviation score or average weekly GH dose. In conclusion, GH treatment was not associated with a reduction in eGFR in short-statured SGA children during puberty. Since low birth weight and prematurity were associated with reductions in eGFR during puberty, monitoring for renal function was mandatory regardless of GH treatment in short-statured children born SGA.

Development and validation of a nomogram to predict poor short-term response to recombinant human growth hormone treatment in children with growth disorders.

The purpose of this study was to develop and validate a clinical predictive model for predicting the likelihood of a poor therapeutic response during the first year of recombinant human growth hormone (rhGH) treatment in children with growth disorders. A total of 627 pediatric patients with growth disorders (GHD, ISS, TS, SGA) from The LG Growth Study cohort were evaluated. Restricted cubic splines (RCS) were utilized to investigate the association between predictors and the risk of poor rhGH response. Variables were selected using LASSO regression, and multivariate logistics regression models were established. Receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC) were used to assess the predictive model's accuracy and clinical value. The predictive accuracy of the model was validated on the testing set. Two predictive models containing 8 baseline predictors (diagnosis, age, height SDS, bone age minus chronological age, rhGH dosage, distance from mid-parental height in SDS, weight SDS, IGF-1 SDS) and 1 post-treatment predictor (height SDS gain at 6months) were constructed by multivariate logistic regression analyses. The nomogram was built based on the multivariate predictive model and showed good discrimination and model fit effects in both the training set and the testing set. DCA and CIC analyses presented good clinical usability. The clinical predictive model for predicting the probability of poor short-term response of rhGH treatment in pediatric patients with growth disorders is useful and can assist physicians in making clinical decisions.

The evolution of pituitary cysts in growth hormone-treated children.

We have previously shown that pituitary cysts may affect growth hormone secretion. This study sought to determine cyst evolution during growth hormone treatment in children. Forty-nine patients with short stature, a pituitary cyst, and at least two brain MRI scans were included. The percent of the pituitary gland occupied by the cyst (POGO) was calculated, and a cyst with a POGO of≤15% was considered small, while a POGO >15% was considered large. Thirty-five cysts were small, and 14 were large. Five of the 35 small cysts grew into large cysts, while 6 of the 14 large cysts shrunk into small cysts. Of 4 cysts that fluctuated between large and small, 3 presented as large and 1 as small. Small cysts experienced greater change in cyst volume (CV) (mean=61.5%) than large cysts (mean=-0.4%). However, large cysts had a greater net change in CV (mean=44.2mm3) than small cysts (mean=21.0mm3). Older patients had significantly larger mean pituitary volume than younger patients (435.4 mm3 vs. 317.9mm3) and significantly larger mean CV than younger patients (77.4 mm3 vs. 45.2mm3), but there was no significant difference in POGO between groups. Pituitary cyst size can vary greatly over time. Determination of POGO over time is a useful marker for determining the possibility of a pathologic effect on pituitary function since it factors both cyst and gland volume. Large cysts should be monitored closely, given their extreme, erratic behavior.

[Efficacy of recombinant human growth hormone treatment in children born small for gestational age with syndromic and non-syndromic short stature].

Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t=1.68, P=0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t=1.52, P=0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z=-2.95, P=0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type (Z=7.65, 2.83 P<0.001, P=0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months (Z=11.95, 7.54, 4.26, 3.83, all P<0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.