Start Of Growth Hormone Treatment 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.

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.

Early GH Treatment Is Effective and Well Tolerated in Children With Turner Syndrome: NordiNet® IOS and Answer Program.

Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS girls with short stature. This work aimed to evaluate the effectiveness and safety of Norditropin (somatropin, Novo Nordisk) with up to 10 years of follow-up in children with TS. Secondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905). A total of 2377 girls with TS were included in the safety analysis set (SAS), with 1513 in the treatment-naive effectiveness analysis set (EAS). At the start of treatment, 1273 (84%) participants were prepubertal (EAS); mean (SD) age was 8.8 (3.9) years. Mean (SD) dose received at the start of GH treatment was 0.045 (0.011) mg/kg/day (EAS). Mean (SD) baseline insulin-like growth factor-1 (IGF-I) SD score (SDS) was -0.86 (1.52), and mean (SD) duration of GH treatment (SAS) was 3.8 (2.8) years.Height SDS (HSDS) increased throughout follow-up, with near-adult HSDS reached by 264 (17%) participants (mean [SD] -1.99 [0.94]; change from baseline +0.90 [0.85]). During the study, 695 (46%) participants (EAS) entered puberty at a mean (SD) age of 12.7 (1.9) years (whether puberty was spontaneous or induced was unknown). Within the SAS, mean IGF-I SDS (SD) at year 10 was 0.91 (1.69); change from baseline +1.48 (1.70). Serious adverse reactions were reported in 10 participants (epiphysiolysis [n = 3]). GH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.

Metabolic Changes across Tertiles of Delta Changes in Height SDS during Growth Hormone Therapy in Children with Growth Hormone Deficiency

Introduction: Obesity, dyslipidemia, hypertension, and insulin resistance are components of the metabolic syndrome and in adults are positively affected by growth hormone (GH) treatment. Few data are available on youth, especially evaluating the improvement of metabolic features after starting GH treatment. The aim of this study was to evaluate changes in metabolic profile in GHD children across tertiles of h-SDS changes after at least 20 months of GH therapy. Methods: Data from 51 normal-weight children and adolescents with GHD (age: 11.4 ± 2.3 years; h-SDS: −2.25 ± −1.94) who had performed a complete metabolic profile including IGF-1, lipid profile (total cholesterol, triglycerides, HDL cholesterol), glucose metabolism (fasting glycemia, insulin, hemoglobin A1c levels), and insulin resistance indices (HOMA, TG/HDL ratio) before and after start GH treatment were analyzed. Subjects who had received GH therapy for at least 20 months were eligible. Delta changes were calculated for each variable. Subjects were divided according to tertiles of delta changes of h-SDS (1st tertile, 2nd tertile, 3rd tertile) before and after a period of GH treatment. Results: In each tertile group, a significant increase in height SDS was documented. Delta changes in glucose metabolism, lipid profile, and insulin resistance indices significantly improved across tertiles groups, showing the highest tertile a better metabolic pattern. Discussion/Conclusions: GH therapy is associated with improvement of metabolic profile. Delta changes seem to be more evident in those children with a higher tertile of delta h-SDS after starting GH therapy. A tailored therapy aimed to reach a proper goal in h-SDS after GH treatment might be necessary in order to reduce cardiovascular risk in GHD children.

Noonan syndrome patients with short stature at a single paediatric endocrinology centre

Introduction: Noonan syndrome (NS) is caused by mutations in RAS/MAPK signalling pathway genes. Growth hormone (GH) treatment is an established yet not fully standardized treatment. Aim: The aim of this article is to assess the first 2 years of GH treatment in NS patients at a single centre. Patients and Methods: A total of 20 (16 males) NS clinically diagnosed regularly followed patients participated (2011–2020). Of these, 9 (45%) had cardiac defects, and 8 (40%) had short stature. Growth hormone deficiency (GHD) was confirmed in 5 patients who started GH treatment, and 2 were treated as short, small for gestational age children. Patients underwent anthropometry, clinical, laboratory and imaging investigations. Results: The mean age at NS diagnosis was 7.8 ± 3.4 years (1.3 ÷ 10.5), and at GH start 9.1 ± 1.5 years. At GH start, SDS height was -3.42±0.58 (-4.1 ÷ -2.6), SDS weight -3.07 ± 0.58 (-3.73 ÷ -2.27), and SDS IGF1 -1.12 ± 0.98 (-2.44 ÷ 0.25). The mean BA at diagnosis was delayed by 2.6 ± 0.9 years. The GH starting dose was 0.035 ± 0.005 mg/kg/d, and changed little thereafter. The growth velocity for the 1 st year of treatment was 8.9 ± 1.4 cm, and for the 2 nd year 6.9±1.1 cm. The first year ΔSDS height was 0.72 (p = 0.002), ΔSDS weight was 0.83 (p = 0.025), the 2 nd year increments being insignificant. The 1 st and 2 nd year ΔSDS IGF1 were 1.70 (p = 0.007) and 0.25 (n.s.), resp. Bone age remained significantly delayed. No treatment side effects were observed. Conclusion: Our study showed that GH-treated NS patients follow the general growth patterns. In order to improve outcomes, the treatment should be further standardized.

Early growth hormone treatment accelerates delayed onset of puberty in patients with growth hormone deficiency.

We investigated whether growth hormone (GH) treatment could accelerate the onset of puberty in patients with isolated GH deficiency (GHD). Of the 135 boys and 89 girls who started GH treatment before the onset of puberty and were followed up at Tanaka Growth Clinic, 83 boys and 51 girls who started GH treatment sufficiently earlier than the average age at onset of puberty of GHD patients (<10 years vs. 11.7 years for boys; <9.5 years vs. 11.4 years for girls) were analyzed. Age at onset of puberty significantly positively correlated to age at the start of GH treatment (boys: r = 0.427, p < 0.0001; girls: r = 0.302, p < 0.05). When the subjects were divided into two groups each: for boys, Groups A (n = 45) and B (n = 39), treatment was started at age <8 and 8 to <10 years, respectively; for girls, Groups A (n = 26) and B (n = 21), treatment was started at age <7 and 7 to <9.5 years, respectively, age at the onset of puberty was significantly lower in Groups A than in Groups B by the Mann-Whitney U test (boys: p < 0.01; girls: p < 0.05) and Kaplan-Meier log-rank test (boys: p < 0.01; girls: p < 0.05). These results indicate that GH treatment accelerates the delayed onset of puberty in patients with GHD. Heights at the onset of puberty in Groups A and B were not significantly different, suggesting that early treatment does not increase adult height.

Demographic characteristics of children with growth hormone deficiency from 1996 to 2015 in Japan: 20 years of data from the foundation for growth science in Japan.

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

Are we late in treating with growth hormone short small for gestational age children? Experience of a tertiary care centre

Background: Short small for gestational age (SGA) children not showing a catch-up growth by 2–4 years of age is an indication for growth hormone (GH) therapy. Objective: The objective of this study was to evaluate at what age short SGA patients present to our paediatric endocrine clinic and start on GH therapy. In addition, we aim to assess their GH response during the 1st year of therapy. Materials and Methods: This retrospective observational study included 108 'SGA' children with 'short stature' who were managed in the paediatric endocrine clinic at Tawam Hospital within 5 years. Patients' electronic medical records were reviewed and their data were retrieved. Results: The median (interquartile range) age at the time of presentation was 6.8 years (3.3, 10.0), with a statistically significant difference between the non-syndromic and syndromic patients, 7.3 (5.2, 10.7) versus 3.2 (1.8, 5.9) years, respectively, whereas the median age at the time of starting GH treatment was 10.7 years (8.1, 13.6), with 47.4% treated at 5–10 years of age and 42.1% at >10 years of age. The mean (±standard deviation) delta height z-score for all treated patients was 0.58 ± 0.40 at 1 year. There was a significant difference in both the mean height at pre and post 1 year of starting GH treatment between the non-syndromic and syndromic groups (P < 0.0001 and 0.003, respectively). Conclusion: The majority of our short SGA patients presented late and were subsequently treated with GH later than the international consensus or guideline recommendations. There is a need for increased awareness to refer these children earlier for a better outcome.

Thyroid Function in Adults with Prader-Willi Syndrome; a Cohort Study and Literature Review.

Prader–Willi syndrome (PWS) is a complex genetic syndrome combining hypotonia, hyperphagia, a PWS-specific neurocognitive phenotype, and pituitary hormone deficiencies, including hypothyroidism. The low muscle mass associated with PWS causes a low energy expenditure due to a low basal metabolic rate. Combined with increased energy intake due to hyperphagia, this results in a high risk of obesity and associated cardiovascular disease. To reduce the high mortality in PWS (3% yearly), exercise is extremely important. As hypothyroidism can impair exercise tolerance, early detection is crucial. We performed a literature search for articles on hypothyroidism in PWS, measured thyroid hormone (TH) levels in 122 adults with PWS, and performed a medical file search for medication use. Hypothyroidism (low free thyroxin) was present in 17%, and often central in origin (80%). Triiodothyronine levels were lower in patients who used psychotropic drugs, while other TH levels were similar. One in six patients in our cohort of adults with PWS had hypothyroidism, which is more than in non-PWS adults (3%). We recommend yearly screening of free thyroxin and thyroid-stimulating hormone levels to avoid the negative effects of untreated hypothyroidism on basal metabolic rate, body mass index, and cardiovascular risk. Additionally, we recommend measuring TH concentrations 3–4 months after the start of growth hormone treatment.

A prediction model could foresee adequate height response in children eligible for growth hormone treatment.

Prediction models may be useful in accurately identifying children who will benefit from growth hormone (GH) treatment. We aimed to validate the Gothenburg prediction model for this purpose. The study included prepubertal children with GH deficiency who started treatment with GH during 2004-2016 at Queen Silvia Children's Hospital, Gothenburg, based on a first-year growth prediction of ≥0.7SDS in height according to the Gothenburg prediction model on a GH dose of 33μg/kg/day. Observed heights retrieved from medical charts were compared with predicted heights. The study included 121 patients (64% boys) with at least one year of data after the start of GH treatment. The median (range) GH dose was 30 (10-43)µg/kg/day for the first year and age at start of treatment was 5.32 (3-11.8)years. The model correctly excluded poor responders resulting in 119/121 (98%) patients having a height gain of at least ≥0.5 SDS in a year. However, the model underestimated relatively low predictions and overestimated relatively high predictions, with a residual standard deviation of 0.31 SDS. By using a validated prediction model for GH in a clinical context, unnecessarily treating short children with an expected poor height outcome can be avoided.

Growth Hormone Stimulation Testing Patterns Contribute to Gender Disparities in Growth Hormone Treatment

Introduction: Growth hormone (GH) registries demonstrate that males outnumber females 2:1 for all indications combined and 3:1 for the idiopathic short stature indication. The aim of this study was to determine if gender disparities in GH treatment are due to differences in rates of stimulation testing and/or GH prescribing. Methods: Retrospective chart review was performed including children aged 2-16 years seen for short stature or poor growth in 2012-2019 at a large tertiary referral center. Children previously diagnosed with GHD were excluded. Continuous variables, reported as medians [IQR], were compared by Wilcoxon rank sum test and categorical variables by Chi-squared test. A two-tailed p-value <0.05 defined statistical significance. Results: Of 10,125 children seen for evaluation of short stature or poor growth (35% [3542] females [F], 65% [6583] males [M]), 1,245 underwent GH stimulation testing (30% [379] F, 70% [866] M). A larger proportion of males than females were tested (M 13.2%, F 10.7%; p <0.001). Amongst the entire study population, females had lower height Z-scores than males (F -1.98 [-2.46, -1.44], M -1.80 [-2.24, -1.31]; p<0.001). This difference persisted in those who proceeded to GH stimulation testing (F -2.52 [-3.00, -2.04], M -2.18 [-2.6, -1.81]; p<0.001) and GH treatment (F -2.62 [-3.11, -2.07], M -2.19 [-2.60, -1.81; p<0.001). Mean difference between height Z-score and mid-parental height (MPH) Z-score for the entire population did not differ by sex (F -1.52 [-2.17, -0.87], M -1.52 [-2.04, -0.97]; p=0.76), but the difference was greater in females among those who underwent GH stimulation testing (F -1.95 [-2.57, -1.40], M -1.79 [-2.32, -1.32]; p=0.009) and started GH treatment (F -1.93 [-2.58, -1.48], M -1.80 [-2.30, -1.32]; p=0.016). Peak stimulated GH levels were similar for males and females (F 9.6 [6.0, 13.6] ng/mL, M 9.4 [6.1, 13.2] ng/mL, p=0.62). The proportion of children prescribed GH after stimulation testing did not differ by gender (F 55% [208], M 56% [488]; p=0.63). This finding did not change upon sub-analysis by peak stimulated GH concentration groups (peak GH concentrations <7 ng/mL, 7-10 ng/mL, and >10 ng/mL). Conclusion: The male predominance among children seen for subspecialist evaluation of short stature was compounded by a greater proportion of those males subsequently undergoing GH stimulation testing despite less severe short stature. Although females who underwent GH stimulation testing had greater height deficit from their genetic potential than tested males, peak stimulated GH concentrations and GH prescription rates were similar by sex. Thus, gender disparities in GH treatment occur at the subspecialist referral and stimulation testing, but not GH prescription, steps. Further, GH stimulation test results failed to account for the more severe shortness among tested females, yet another limitation identified with such testing.

Factors influencing growth hormone therapy effect during the prepubertal period in small for gestational age children without catch-up growth

PurposeBecause small for gestational age (SGA) children who fail to experience catch-up growth have an increased risk of short stature in adulthood, growth hormone (GH) treatment is recommended for effective growth. In this study, we evaluated the effect of GH treatment during the prepubertal period and analyzed for correlation between GH treatment response and clinical factors in SGA children.MethodsA retrospective, single-center study was conducted from 2014 to 2020. A total of 34 prepubertal children of short stature up to 4 years of age and born as SGA were enrolled. We recorded clinical data including birth data, age, weight, height, bone age (BA), and insulin-like growth factor 1 (IGF-1) levels.ResultsThe mean gestational age and birth weight were 37.50±2.51 weeks and 2,200.00±546.79 g. At the start of GH treatment, the mean chronological age and BA were 5.54±1.73 years and 4.52±1.85 years, respectively. The height standard deviation score (SDS) (-2.47±0.45) and IGF-1 SDS (0.16±1.57) were calculated. Height velocity was 9.43±1.40 cm during the first GH treatment year and 7.63±1.16 cm during the second year (P<0.05). The treatment growth response was positively correlated with young age (P=0.047) and lower BA (P=0.049) at the start of treatment. In multiple regression analysis, IGF-1 SDS change had a significantly positive association with GH treatment response (P=0.045).ConclusionsGH treatment is effective for short stature SGA children who do not experience catch-up growth. Early initiation of GH treatment improved growth outcomes. As IGF-1 SDS is positively correlated with height SDS, IGF-1 monitoring is important during GH treatment of SGA prepubertal children.

Early start of growth hormone is associated with positive effects on auxology and metabolism in Prader-Willi-syndrome

BackgroundPrader-Willi-Syndrome (PWS) is characterized by hypothalamic-pituitary dysfunction. Recent research suggests starting growth hormone-treatment (GHT) as soon as possible. The aim of this study is to analyze possible differences in auxological parameters, carbohydrate and lipid metabolism between two groups of children with PWS that started GHT either during or after their first year of life.Study designRetrospective longitudinal study of 62 children (31 males) with genetically confirmed PWS. Upon diagnosis all children were offered GHT, some started immediately, others commenced later. Cohort A (n = 21; 11 males) started GHT at 0.3–0.99 yrs. (mean 0.72 yrs) and Cohort B (n = 41; 20 males) commenced GHT at 1.02–2.54 yrs. (mean 1.42 yrs) of age. Fasting morning blood samples and auxological parameters were obtained before the start of therapy and semi-annually thereafter. Differences between the two cohorts were estimated with a linear mixed-effect model.ResultsMean length/height-SDSPWS differed significantly between the groups [1 yr: A: 0.37 (±0.83) vs B: 0.05 (±0.56); 5 yrs.: A: 0.81 (±0.67) vs B: 0.54 (±0.64); p = 0.012]. No significant differences were found in BMI, lean body mass or body fat.Low-density cholesterol was significantly lower in A than in B [LDL: 1 yr: A: 79 (±20) mg/dl vs B: 90 (±19) mg/dl; 5 yrs.: A: 91(±18) mg/dl vs 104 (±26) mg/dl; p = 0.024].We found significant differences in the glucose homeostasis between the groups [fasting insulin: p = 0.012; HOMA-IR: p = 0.006; HbA1c: p < 0.001; blood glucose: p = 0.022].ConclusionsAn early start of GHT during the first year of life seems to have a favorable effect on height-SDS and metabolic parameters.

Growth Hormone Treatment at Nippon Medical School Chiba Hokusoh Hospital.

Since 2002, the Department of Pediatrics of Nippon Medical School Chiba Hokusoh Hospital has offered educational activities for children with short stature. We analyzed outcomes of growth hormone (GH) treatment for children with short stature treated at our hospital, particularly outcomes after the growth spurt. We analyzed data from children aged 0 to 17 years who were treated with recombinant GH during the period from 2000 through 2016 and were followed for at least 2 years after the start of treatment. Among children with short stature, 85 had GH deficiency, 5 had Turner syndrome, 9 were small for gestational age, and 1 had Noonan syndrome. The outcomes of GH treatment was similar to those previously reported in Japan. Children with GH deficiency who started GH treatment before the growth spurt exhibited marked height catch-up until the second year, but the effect decreased after 3 years. The effect of treatment for GH deficiency that was started after the growth spurt continued for 4 to 5 years after the start of treatment. Improvement in height standard deviation score was similar when treatment was started before and after the growth spurt.

Final Adult Height after Growth Hormone Treatment in Patients with Turner Syndrome

Aims: This study aimed to evaluate final adult height (AH) after recombinant human growth hormone (GH) treatment of girls with Turner syndrome (TS) and to elucidate the predicting factors for their growth response. Methods: We enrolled 73 patients with TS who underwent GH treatment and reached AH and 14 patients who did not undergo treatment. To assess the effectiveness of GH therapy, we evaluated final AH, height gain over the predicted AH, and height gain over the projected AH. In addition, to analyze the factors affecting final AH, we studied correlations between final AH (or height SDS, height gain) and treatment variables. Results: GH therapy was started at a mean age of 8.87 ± 3.73 years, and the treatment duration was 6.47 ± 3.02 years. The patients in the treated group reached a final AH of 152.03 ± 4.66 cm (final AH SDS for the general population: –1.93 ± 1.03) with a gain over projected AH at the start of treatment of 12.21 ± 4.33 cm. The untreated control subjects had a final AH of 143.57 ± 4.06 cm with a gain over projected AH at the first visit of 3.89 ± 3.80 cm. Final AH and AH SDS were positively correlated to height SDS at the start of treatment. Thirty-five patients out of the 73 GH-treated patients (47.9%) attained to a normal range of height for Korean girls. The patients having attained to a normal height range after GH treatment had shown a higher height SDS at the start of GH treatment, a higher mid-parental height SDS, and a younger age at initiation of estrogen. Conclusions: Our findings demonstrate that GH treatment at an early age is effective in improving the final height SDS and height SDS gain in TS patients. Therefore, GH administration at an early age is important for final height gain.

Adherence to growth hormone (GH) therapy in na\xefve to treatment GH-deficient children: data of the Italian Cohort from the Easypod Connect Observational Study (ECOS)

BackgroundWith the use of non-objective measurement, adherence to growth hormone (GH) therapy has been reported suboptimal in a large proportion of patients, and poor adherence has been shown to affect short-term growth response in patients receiving GH treatment.ObjectiveThe Easypod™ electronic device allows objective measurement of adherence. In this study, we report 3-year prospective adherence data of the Italian cohort of naïve GH deficient (GHD) children extrapolated from the Easypod Connect Observational Study (ECOS) database.Patients and methodsSeventy-three GHD children naïve to GH treatment were included in the analysis. 22 Italian centers participated in the study.ResultsMean adherence rate was consistently above 85% across the 3-year observation period. Particularly, mean adherence was 88.5%, 86.6%, and 85.7% after 1, 2 and 3 years, respectively. Mean (± SD) height-SDS increase after the first year was 0.41 (± 0.38).ConclusionsThe majority of naïve GHD children starting GH treatment with Easypod maintained an adherence rate > 85% up to 3 years. Easypod is a useful tool to follow-up patients’ adherence allowing timely intervention to improve optimal treatment for these patients.

First-year predictors of health-related quality of life changes in short-statured children treated with human growth hormone.

Little attention has been directed towards examining the impact of predictors on change in health-related quality of life (HRQOL) within the course of growth hormone (GH) treatment in pediatric short stature. We aimed to assess changes in HRQOL and its sociodemographic, clinical and psychosocial predictors in children and adolescents diagnosed with growth hormone deficiency (GHD), and born short for gestational age (SGA) before and 12-month after start of GH treatment from the parents' perspective. Results were compared with an untreated group with idiopathic short stature (ISS). In this prospective multicenter study, 152 parents of children/adolescents (aged 4-18years) provided data on their children's HRQOL at baseline and at 12-month follow-up. Repeated-measures multivariate analyses of covariance were performed to examine parent-reported HRQOL changes from baseline to 1-year after treatment and hierarchical linear regressions to identify the predictors of HRQOL changes. Results showed that parents of children that were treated with GH report an increase in their children's HRQOL after 1year. Changes in HRQOL were mostly explained by psychosocial predictors followed by sociodemographic and clinical variables. Specifically, the diagnosis SGA significantly predicted a greater increase in parent-reported HRQOL. Furthermore, a lower caregiving burden significantly predicted a decrease in parent-reported HRQOL. In conclusion, a substantial percentage of explained variance in HRQOL relates to psychosocial and sociodemographic predictors. However, there appears to be other important factors that are predictors of HRQOL, which need to be determined in large, population-based samples.

Comparison of effectiveness of growth hormone therapy according to disease-causing genes in children with Noonan syndrome.

PurposeTo analyze the growth response to growth hormone (GH) therapy in prepubertal patients with Noonan syndrome (NS) harboring different genetic mutations.MethodsTwenty-three patients with prepubertal NS treated at Pusan National University Children’s Hospital between March 2009 and July 2017 were enrolled. According to the disease-causing genes identified, the patients with NS were divided into 4 groups. Three groups were positive for mutations of the PTPN11, RAF1, and SOS1 genes. The five genes undetected (FGU) group was negative for PTPN11, RAF1, SOS1, KRAS, and BRAF gene mutations. The influence of genotype was retrospectively analyzed by comparing the growth parameters after GH therapy.ResultsThe mean chronological age at the start of GH treatment was 5.85±2.67 years. At the beginning of the GH treatment, the height standard deviation score (SDS), growth velocity (GV), and lower levels of insulin-like growth factor-1 (IGF)-1 levels were not statistically different among the groups. All the 23 NS patients had significantly increased height SDS and serum IGF-1 level during the 3 years of treatment. GV was highest during the first year of treatment. During the 3 years of GH therapy, the PTPN11, RAF1, and SOS1 groups showed less improvement in height SDS, IGF-1 SDS, and GV, and less increase in bone age-to-chronological age ratio than the FGU group.ConclusionThe 3-year GH therapy in the 23 prepubertal patients with NS was effective in improving height SDS, GV, and serum IGF-1 levels. The FGU group showed a better response to recombinant human GH therapy than the PTPN11, RAF1, and SOS1 groups.

Early adiposity rebound in patients with Prader-Willi syndrome.

Background Prader-Willi syndrome (PWS) is associated with marked obesity that can lead to severe complications such as diabetes mellitus. Early adiposity rebound (AR) is associated with future obesity and an increased risk of diabetes mellitus and metabolic syndrome. Previous reports have shown that the onset of AR occurred earlier in diseases that cause obesity. However, there have been no studies focusing on the timing of AR in PWS, or on the effect of growth hormone (GH) treatment on AR. The aim of this study was to explore AR in PWS patients and to analyze the effect of GH treatment on AR. Methods This retrospective study evaluated 48 patients, with 16 of the patients found to have AR prior to GH treatment. AR was constructed for each patient using Microsoft Excel, and the exact point of the nadir of body mass index (BMI) following the initial peak was determined. We additionally analyzed the relationship between GH treatment and the timing of AR onset. Results AR onset for patients found to have AR before starting GH treatment was 16.0 (13.0-21.0) months. In contrast, AR onset for patients found to have AR after starting GH treatment was 27.5 (23.8-36.3) months. The difference between the two groups was statistically significant (p=0.0001). A positive correlation was found between the GH treatment period and AR (p=0.00013). Conclusion The median age of AR onset in PWS patients was 16.0 (13.0-21.0) months, and GH treatment might delay the early AR onset.

Racial/Ethnic Disparities in US Pediatric Growth Hormone Treatment

Background/Aims: To compare racial/ethnic proportions of subjects receiving growth hormone (GH) treatment to the expected proportions, and secondarily, to assess racial/ethnic differences in subject characteristics at GH treatment initiation. Methods: Race/ethnicity-based expected frequencies of height <–2.25 SD were determined by applying relative risks for short stature, calculated from a regional population of 189,280 pediatric primary care patients, to US census data, and compared to racial/ethnic proportions of US subjects enrolled in the Pfizer International Growth Study (KIGS) using the χ² test. Characteristics of white and black subjects at GH treatment initiation were presented as medians and compared by the Wilcoxon rank sum test (significant p < 0.01). Results: White subjects exceeded the expected frequency (63%) for all indications (83%) and each separately, ranging from 73% for congenital GH deficiency (GHD) to 85% for idiopathic short stature (p < 0.001). Compared to white subjects, black subjects treated for idiopathic GHD had greater height deficits relative both to the population (–2.97 vs. –2.56 SD) and to their mid-parental heights (–2.47 vs. –1.89 SD), lower stimulated GH peak levels (4.9 vs. 6.0 ng/mL), and lower birth weights (–0.86 vs. –0.48 SD). Black subjects with congenital GHD had lower stimulated GH peaks (2.1 vs. 3.2 ng/mL) and started GH treatment at younger ages (2.9 vs. 4.8 years), while those with acquired GHD had lower birth weights (–1.12 vs. –0.08 SD). Male predominance did not differ by race for any or all indications. Conclusion: Overrepresentation of white children among those receiving GH treatment in the US KIGS registry reflects racial/ethnic treatment biases, not just differences in growth rates.