Human Growth Hormone Treatment Research Articles

Improvement of Bone Metabolism in Prepubertal Girls with Turner Syndrome Following Long-term Pegylated Growth Hormone Treatment.

The study aims to assess the improvement in bone metabolism in prepubertal girls with Turner Syndrome (TS) after long-term polyethylene glycol recombinant human Growth Hormone (PEG-rhGH) treatment. A 12-month longitudinal prospective study was conducted with 28 prepubertal girls diagnosed with TS. Participants were divided into two groups: 18 received PEG-rhGH therapy (0.1-0.25 mg/kg/week) and 10 did not. Anthropometric measurements, bone turnover markers (BTMs), and serum levels of IGF-1, calcium, and phosphate were collected at baseline and after 12 months. BTMs included bone alkaline phosphatase (BAP), Type I collagen propeptide (CICP), Type I collagen telopeptide (CTX), and fibroblast growth factor 23 (FGF23). After 12 months of PEG-rhGH therapy, the treatment group showed significant increases in growth velocity (GV) and height standard deviation scores (HtSDS). Serum IGF-1 levels increased rapidly within one month and remained elevated. BTMs indicated enhanced bone formation, significantly increasing BAP and CICP, while CTX levels remained low. FGF23 levels initially rose slightly but declined below baseline by 12 months. Elevated blood phosphate levels were observed. PEG-rhGH therapy in children with TS significantly improves linear growth and enhances bone formation markers, benefiting bone metabolism.

6778 Visual Presentations for Adherence Risk Management In Patients Receiving Recombinant Human Growth Hormone Therapy

Abstract Disclosure: P. van Dommelen: Consulting Fee; Self; PvD has a consultancy agreement with Merck KGaA, Darmstadt, Germany. F. Michelis: Employee; Self; FL is an employee of Ares Trading SA, an affiliate of Merck KGaA. L. Arnaud: Employee; Self; LA is an employee of Ares Trading SA, an affiliate of Merck KGaA. S. Loche: Advisory Board Member; Self; SL has received advisory board fees from Merck KGaA, Darmstadt, Germany. Consulting Fee; Self; SL has received consultancy fees from Merck KGaA, Darmstadt, Germany. Speaker; Self; SL has received lecture fees from Merck KGaA, Darmstadt, Germany. E. Koledova: Employee; Self; EK is an employee of Merck KGaA,Darmstadt, Germany. Stock Owner; Self; EK holds shares in Merck KGaA, Darmstadt, Germany. Background: A data-driven clinical decision support system based on visual presentations for adherence risk management can support patients receiving recombinant human growth hormone (r-hGH) treatment. Our focus is on examining adherence patterns during the first 6 weeks of treatment, with a particular emphasis on the days of the week, the variability in injection timings and the summer holiday. Our aim is to assess whether these early patterns can serve as indicators for predicting adherence in the subsequent 7-12 weeks of treatment. Data and Methods: Adherence data between March-November 2023 were extracted from the newly launched third generation of easypod™ device (EP3) and GrowZen Connect Next ecosystem. EP3 is the only connected device that delivers r-hGH and monitors real-time adherence to therapy. EP3 was perceived by health care professionals as more intuitive, comfortable, user-friendly, simpler, and easier to use than previous EP2. Patients with age 2-18 years at treatment start, a 7-day regimen and complete adherence data available between 1-12 weeks of treatment were selected. Data about sex, age at start treatment, as well as adherence, classified as high (≥95%) versus low/medium <95%), standard deviation (SD) of adherence (%), log (to adjust for skewness) of the interquartile range (IQR) of the timing of injection throughout the day, median timing of the injection after midnight, and ≥50% versus <50% of the injections fall in the summer period (July-August) aggregated by day over the first 6 weeks of treatment were included in a generalized linear mixed model with adherence between 7-12 weeks as outcome. Results: In total, data for 232 patients (124 boys and 108 girls, median (Q25-Q75) age at treatment start was 10.5 (7.6-12.3)) were available. The model showed no difference in effect of adherence rates during Monday-Thursday. We, therefore, aggregated the data by weekday (Monday-Thursday) versus weekend day (Friday-Sunday, Friday was included due to the common practice of administering injections during the evening). Adherence, SD of adherence, IQR of timing of injections, and injections falling in summer were significant (p<0.05) predictors of adherence during a weekday and weekend between 7-12 weeks. Areas under the curves were both 0.96 during the weekday and weekend. Conclusions: Our research shows that adherence and timing of injections, as well as taking into account the summer holidays, can predict future adherence accurately. Visual presentations showing aggregated adherence rates and variation of timing of injections by days of the week, as well as highlighting the summer periods may improve adherence risk management and timely support. Presentation: 6/3/2024

7548 Final adult height in children with idiopathic growth hormone deficiency after growth hormone treatment

Abstract Disclosure: H. Lee: None. S. An: None. M. Cho: None. H. Nam: None. Objective: The aim of this study was to assess the final adult height (FAH) achieved through recombinant human growth hormone (GH) treatment and the factors influencing FAH. Methods: We retrospectively reviewed the charts of all patients diagnosed with IGHD who were prepubertal when they began GH treatment since August 2007. FAH was determined in 41 patients (28 males and 13 females) by July 2023. Results: 41 patients started treatment at an average age of 9.1 years and continued for 6.5 years. The mean initial height was -2.6 standard deviation scores (SDS) and the mean FAH was -0.6 SDS. GH treatment was initiated at a significantly younger age in females than in males (7.2±1.9 vs 10.0±3.2; p=0.01). The mean FAH was 169.9±4.5cm for males and 156.1±3.2cm for females. Differences between initial height and final height SDS were not significant between males and females. The mean of FAH SDS was higher compared to their mid-parental height -1.0 SDS (p=0.017). In multiple regression analysis, FAH showed a positive correlation with initial height, duration of treatment, and growth rate in the first year of treatment, and a negative correlation with BMI SDS at the start of GH (r2=0.59; p=0.000). FAH SDS was positively related to initial height SDS and growth rate in the first year of treatment. (r2=0.3; p=0.001) Conclusions: The mean FAH SDS after GH treatment was significantly higher than the mean MPH SDS in IGHD patients. Moreover, the good response of GH treatment was associated with longer treatment duration, greater height at the start of treatment, better treatment response at 1 year, and lower initial BMI SDS. Presentation: 6/3/2024

6877 Withdrawing Growth Hormone Treatment at Mid-Puberty in Idiopathic Isolated Growth Hormone Deficiency: Baseline Characteristics in Patient-Preference Design Study

Abstract Disclosure: J. Vliegenthart: None. J. Wit: None. B. Bakker: None. A. Boot: None. C. de Bruin: None. M. Finken: None. J.V. Heyden: None. M. Houdijk: None. H. van der Kamp: None. E. Van Mil: None. A. Reedijk: None. T. Sas: None. D.A. Schott: None. P. van Setten: None. S. Straetemans: None. V. van Tellingen: None. B. Touwslager: None. A.V. Trotsenburg: None. P. voorhoeve: None. A.C. Hokken-Koelega: None. D.C. van der Kaay: None. Background: The majority of children diagnosed with idiopathic isolated growth hormone deficiency (IIGHD) show a normal growth hormone (GH) secretion (assessed by GH stimulation tests) when retested at near adult height (NAH). It appears plausible that, if normal stimulated GH secretion is observed in mid-puberty, continuing recombinant human GH (rhGH) treatment may only have a minor effect on NAH. The effect on NAH has never been investigated in a prospective study. Aim: To evaluate patient preference in the choice to (dis-)continue GH treatment from mid-puberty, and to study whether patients who discontinued treatment differed in baseline characteristics from those who continued treatment. Methods: The study population consisted of adolescents who were diagnosed in childhood with IIGHD (GH peak at diagnosis between 1.7 ug/L and 10 ug/L) and who had started rhGH therapy between 2005-2018. According to the national treatment protocol, GH secretion was retested in mid-puberty (males: Tanner stage G3/4, testicular volume >12 ml and bone age (BA) 13-16 years; females: Tanner stage B3/4 and BA 11-14 years). In this multicentre prospective patient-preference design study, adolescents who tested GH sufficient at mid-puberty (GH peak >6.7 ug/L) had the choice to discontinue or continue rhGH treatment until NAH (height velocity <2cm/year). Results: In total 127 patients (95 male, 75%) participated in this study. Forty-four patients (35%) chose to continue GH treatment until NAH (group 1), and 83 patients (65%) chose to discontinue GH treatment (group 2). Mean height at inclusion (group 1: -0.76±0.69 SDS vs group 2: -0.47±0.85 SDS; P=0.055), target height SDS (group 1: -0.73±0.54 SDS and -0.58±0.53 SDS, P=0.15) and age at inclusion (group 1: 14.0±1.1y and 13.9±1.1y, P=0.69) did not significantly differ between groups. Males and females did not differ in these characteristics. Currently, 109 patients (86%) have reached NAH. Conclusions: The majority of patients (65%) preferred to discontinue rhGH treatment after sufficient GH retesting in mid-puberty. An anticipated difference in baseline data between the groups (adolescents who choose to discontinue treatment may be taller and older) could not be confirmed. Data are being collected until all patients reach near adult height. Presentation: 6/3/2024

9262 Withdrawing Growth Hormone Treatment at Mid-Puberty in Idiopathic Isolated Growth Hormone Deficiency: Baseline Characteristics in Patient-Preference Design Study

Abstract Disclosure: J. Vliegenthart: None. J. Wit: None. B. Bakker: None. A. Boot: None. C. de Bruin: None. M. Finken: None. J.V. Heyden: None. M. Houdijk: None. H. van der Kamp: None. E. Van Mil: None. A. Reedijk: None. T. Sas: None. D.A. Schott: None. P. van Setten: None. S. Straetemans: None. V. van Tellingen: None. B. Touwslager: None. A.V. Trotsenburg: None. P. voorhoeve: None. A.C. Hokken-Koelega: None. D.C. van der Kaay: None. Background: The majority of children diagnosed with idiopathic isolated growth hormone deficiency (IIGHD) show a normal growth hormone (GH) secretion (assessed by GH stimulation tests) when retested at near adult height (NAH). It appears plausible that, if normal stimulated GH secretion is observed in mid-puberty, continuing recombinant human GH (rhGH) treatment may only have a minor effect on NAH. The effect on NAH has never been investigated in a prospective study. Aim: To evaluate patient preference in the choice to (dis-)continue GH treatment from mid-puberty, and to study whether patients who discontinued treatment differed in baseline characteristics from those who continued treatment. Methods: The study population consisted of adolescents who were diagnosed in childhood with IIGHD (GH peak at diagnosis between 1.7 ug/L and 10 ug/L) and who had started rhGH therapy between 2005-2018. According to the national treatment protocol, GH secretion was retested in mid-puberty (males: Tanner stage G3/4, testicular volume >12 ml and bone age (BA) 13-16 years; females: Tanner stage B3/4 and BA 11-14 years). In this multicentre prospective patient-preference design study, adolescents who tested GH sufficient at mid-puberty (GH peak >6.7 ug/L) had the choice to discontinue or continue rhGH treatment until NAH (height velocity <2cm/year). Results: In total 127 patients (95 male, 75%) participated in this study. Forty-four patients (35%) chose to continue GH treatment until NAH (group 1), and 83 patients (65%) chose to discontinue GH treatment (group 2). Mean height at inclusion (group 1: -0.76±0.69 SDS vs group 2: -0.47±0.85 SDS; P=0.055), target height SDS (group 1: -0.73±0.54 SDS and -0.58±0.53 SDS, P=0.15) and age at inclusion (group 1: 14.0±1.1y and 13.9±1.1y, P=0.69) did not significantly differ between groups. Males and females did not differ in these characteristics. Currently, 109 patients (86%) have reached NAH. Conclusions: The majority of patients (65%) preferred to discontinue rhGH treatment after sufficient GH retesting in mid-puberty. An anticipated difference in baseline data between the groups (adolescents who choose to discontinue treatment may be taller and older) could not be confirmed. Data are being collected until all patients reach near adult height. Presentation: 6/3/2024

Effects of combined human growth hormone and leuprolide treatment on growth and bone metabolism in girls with adolescent idiopathic short stature.

Effects of combined human growth hormone and leuprolide treatment on growth and bone metabolism in girls with adolescent idiopathic short stature.

Factors affecting growth hormone treatment in short stature children born small for gestational age in China: a single-centre, real-world study.

The study aimed to evaluate the factors influencing recombinant human growth hormone (rhGH) treatment in Chinese children with short stature born small for gestational age (SGA). A single-centre, real-world retrospective study was conducted in short stature children born SGA in China. Outcomes were observed at 6, 12, 18, 24, 30, and 36 months. Outcome measures included height standard deviation score (HTSDS), height, growth velocity (GV), and change of HTSDS (ΔHTSDS). The study used the generalized estimating equation (GEE) to identify potential influencing factors, such as rhGH treatment duration, age at rhGH initiation, sex, 11p15 hypomethylation, GH secretion, and birth weight. A subgroup analysis was conducted to investigate the impact of 11p15 hypomethylation related to SGA or impaired GH secretion. Of all 101 SGA patients included in the screening, 41 were eligible for inclusion in the study. The mean age at rhGH initiation was 5.6 ± 2.4 years. The results of the GEE analysis showed a significant association between time after rhGH initiation and HTSDS, height, GV, and ΔHTSDS. GV increased after treatment, with the highest increase observed in the first six months. Additionally, the study found negative correlations between 11p15 hypomethylation and GV, as well as between birth weight and both GV and ΔHTSDS. The study found a positive correlation between impairment in GH secretion and both GV and ΔHTSDS. No statistically significant difference was observed in the comparison of GV or ΔHTSDS between the initiation age of GH treatment and 11p15 hypomethylation. After 24 and 30 months of rhGH treatment, patients with impaired GH secretion had significantly higher ΔHTSDS scores. In short stature Chinese children born SGA, those without SGA-related 11p15 hypomethylation or with impaired GH secretion showed better response to rhGH treatment. These findings highlight the importance of pre-treatment evaluation, including genetic and endocrine assessments.

Over Three Decades of Growth Hormone Treatment in Children With Chronic Kidney Disease-Associated Growth Failure Before and After Kidney Transplantation.

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. 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.

The growzen™ buddy smartphone app to improve adherence in patients receiving recombinant human growth hormone therapy: a retrospective observational study in Argentina.

This study in Argentina evaluated the impact of the growzen™ buddy smartphone app on adherence to recombinant human growth hormone (r-hGH) treatment. The adherence data, invitation dates with a link to the app, app activation dates, and height measurements entered were extracted from the growzen™ digital health ecosystem. Patients with 12 months of adherence data, aged ≥2 years at treatment start, and aged <19 years were selected both before and after app implementation. Mean adherence was classified as optimal (≥85%) versus suboptimal (<85%). Adherence before and after implementation and the pre-post effect on adherence were assessed. Data for 830 patients were available. Prior to app implementation, the proportion of patients with optimal adherence was 68% (n = 348/515). Following the app implementation, out of 315 patients, 302 (96%) received an invitation with a link to the app, 225 (71%) activated their account, and 127 (40%) entered height data in the first year. There was a significant early increase in the proportion of patients with optimal adherence following implementation: 82% (n = 258/315), p < 0.001. After implementation, the proportion of patients with optimal adherence included 80% (n = 78/98) of those with an active account who did not enter height measurements and 89% (n = 113/127) of those who did. There was a significant and positive pre-post app effect on adherence (p < 0.01) in patients with an active account. Our results show that using the growzen™ buddy app has a rapid and positive impact on adherence to r-hGH treatment, and patients who were more engaged with the app demonstrated better adherence.

Changes in body proportions and body fat content in GH-deficient and non-GH-deficient children during the first year of growth hormone treatment.

Introduction: The growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) is crucial for longitudinal bone growth and exerts several metabolic effects. It is debatable whether and how the recombinant human growth hormone (rhGH) treatment affects the trunk-limb proportions. Aim of the study: We aim to evaluate the changes in body proportions and body fat content in short children with growth hormone deficiency (GHD), children born small for gestational age (SGA), and girls with Turner syndrome (TS) during the first year of rhGH therapy. Material and methods: The data of 70 children with GHD, 40 children born SGA, and 36 girls with TS from 1998 to 2019 were analyzed. The following parameters were measured: height, body weight, sitting height, and two skinfolds on the arm above the triceps brachii and below the scapula at the beginning of rhGH therapy and after the first year of treatment. Sitting height and lower limb length were presented as percentages (%) of body height. Fat mass percentage (%FAT) was calculated using the Slaughter formula. Results: At the beginning of rhGH, TS girls had the greatest height deficit (-2.7 SDS), the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and children born SGA. Moreover, TS girls had higher body weight SDS, BMI SDS compared to SGA children (p < 0.001), and higher %FAT compared to both GHD and SGA children (p < 0.001 for both). After the first year of rhGH therapy, a significant increase in lower limb share (%) and a decrease in %FAT were observed in all the study groups. TS girls still had significantly higher sitting height (%), shorter lower limbs (%), and higher %FAT, body weight SDS, and BMI SDS compared to children with GHD and children born SGA (p < 0.05 for all variables). Conclusions: Our results show that rhGH treatment could increase lower limb length in relation to height and reduce fat mass in treated children. Girls with TS had the largest baseline body disproportions and the highest body fat content. Despite a satisfactory reduction in height deficit, after the first year of rhGH therapy, these girls had still higher body weight SDS, BMI SDS, %FAT, the highest sitting height (%), and the lowest lower limb length (%) compared to children with GHD and born SGA.

Heightism, growth hormone treatment, and social functioning: a holistic approach to a persistent clinical challenge.

Use of recombinant human growth hormone (rhGH) treatment to increase height in children with non-growth hormone deficient short stature is becoming more common. Yet, the evidence to support the notion that augmenting height directly leads to increased well being, specifically psychosocial well being, is inconsistent, with high-quality evidence lacking. Review of recent studies demonstrates that the association between height augmentation and psychosocial well being is complex. The direct contribution of height to well being may be less than the current model of clinical care of short stature assumes. Rather, the new studies provide evidence to support a role for psychosocial factors, including height-related beliefs, social support, and coping skills, in promoting psychosocial well being, specifically quality of life and self-esteem. Clinical care of short stature would benefit from incorporating a holistic model of care that considers psychosocial interventions in addition to, or instead of, rhGH treatment.

Optimal final adult height achieved by low-dose recombinant human growth hormone therapy.

Thailand has been administering the recombinant human growth hormone (rhGH) treatment for >20 years. Due to limited resources being available, efforts have been directed toward utilizing rhGH at the lowest feasible dose. However, there is currently a lack of evidence in terms of the efficacy and outcomes. To evaluate the auxological outcomes of growth hormone (GH) treatment and the GH secretion ability after reaching final adult height (FAH) and discontinuing rhGH. Data of 40 patients were retrospectively reviewed. The clinical characteristics, auxological data, and results of biochemical and endocrine investigations before and during rhGH treatment were evaluated. In addition, GH retesting was performed in 24 patients using the insulin tolerance test. Twenty patients (50%) had complete growth hormone deficiency (GHD), defined as peak stimulated GH level <5 ng/mL, and the remaining patients had partial GHD. Most patients were male (n = 25, 62.5%). The mean age at which rhGH was initiated was 8.9 years. Patients with partial GHD received a higher dose of rhGH than those with complete GHD (30.9 µg/kg/d vs. 26.2 µg/kg/d, P = 0.02). Patients with complete and partial GHD reached FAH at height standard deviation scores (SDSs) of -0.65 and -1.47, respectively. The factors associated with obtaining a good clinical response in terms of height gain included peak-stimulated GH level, age of puberty, and age of discontinuing rhGH. After completing the rhGH treatment, 13 of the 24 patients showed normal GH secretion. Patients with multiple pituitary hormone deficiency (MPHD) were likely to have persistent GHD through adulthood (n = 8, 88.9%). This study has demonstrated that the use of low-dose rhGH could result in healthy populations achieving optimal FAHs. Patients with MPHD might not require retesting as they were likely to have persistent GHD. The results obtained in this research highlight the benefits of the treatment. This treatment can be applied in resource-limited countries.

Rare Cases of Iatrogenic Alzheimer's Disease Linked to Banned Human Growth Hormone Treatment

Rare Cases of Iatrogenic Alzheimer's Disease Linked to Banned Human Growth Hormone Treatment

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.

The Effect of Human Growth Hormone Treatment on the Development of Slipped Capital Femoral Epiphysis: A Cohort Analysis With 6 Years of Follow-up.

Slipped capital femoral epiphysis (SCFE) is a common hip disorder in adolescents that can result in substantial complications, impacting the quality of life. Human Growth Hormone (HGH) administration may elevate the risk of SCFE, though the relationship remains unclear. Clarifying this association could enable better monitoring and earlier diagnosis of SCFE in patients receiving HGH. The aim of the study is to investigate the association between HGH administration and the incidence of SCFE. This retrospective cohort study utilized data from the TriNetX research database from January 2003 to December 2022. The study included 2 cohorts: an HGH cohort including 36,791 patients aged below 18 years receiving HGH therapy and a control group consisting of patients who did not receive HGH therapy. A 1:1 propensity score matching technique was employed to ensure comparability between the HGH and no-HGH cohorts. The primary outcome measure was the development of SCFE identified by International Classification of Diseases codes. For comparative analysis, both risk ratios (RR) and hazard ratios were computed to evaluate the association between HGH therapy and the development of SCFE. The HGH cohort had an increased risk of SCFE compared with the no-HGH cohort (RR: 3.5, 95% CI: 2.073, 5.909, P <0.001) and had an increased hazard of developing SCFE (hazard ratio: 2.627, 95% CI: 1.555, 4.437, P <0.001). Patients with higher exposure to HGH (defined as >10 prescriptions) had an RR of 1.914 (95% CI: 1.160, 3.159, P =0.010) when compared with their counterparts with ≤10 prescriptions. In the largest study to date, HGH administration was associated with an elevated risk of SCFE in children in a dose-dependent manner. Level III-therapeutic retrospective cohort study.

Molecular diagnosis is an important indicator for response to growth hormone therapy in children with short stature

BackgroundSignificant differences have been observed in the efficacy of recombinant human growth hormone (rhGH) treatment for short children. The present study aimed to identify the genetic etiology of short stature and to assess the role of molecular diagnosis in predicting responses to rhGH treatment. MethodsA total of 407 short children were included in the present study, 226 of whom received rhGH treatment. Whole-exome sequencing (WES) was conducted on short children to identify the underlying genetic etiology. Correlations between molecular diagnosis and the efficacy of rhGH treatment were examined. ResultsPathogenic or likely pathogenic mutations were identified in 86 of the 407 patients (21.1%), including 36 (41.9%) novel variants. Among the multiple pathways affecting short stature, genes involved in fundamental cellular processes (38.7%) play a larger role, especially the RAS-MAPK pathway. In general, patients without pathogenic mutations responded better to rhGH than those with mutations. Furthermore, patients with hormone signaling pathway mutations had a better response to rhGH, while those with paracrine factor mutations had a worse response to rhGH. ConclusionsThis study highlights the utility of WES in identifying genetic etiology in children with short stature. Identifying likely causal mutations is an important factor in predicting rhGH response.

Evaluating the effect of recombinant human growth hormone treatment on sleep-related breathing disorders in toddlers with Prader–Willi syndrome: a one-year retrospective cohort study

BackgroundRecombinant human growth hormone (rhGH) therapy is beneficial for children with Prader–Willi syndrome (PWS) in improving short stature and metabolism, but the effect of early rhGH treatment on respiratory and sleep parameters for PWS children under three years old remains elusive. Thus, this study aimed to investigate the impact of rhGH treatment on sleep-related breathing disorders (SRBDs) for toddlers with PWS.MethodsA total of 17 age-matched PWS patients receiving rhGH treatment (rhGH group) and 17 control individuals not receiving rhGH treatment (non-rhGH group) were recruited for this study between October 2018 and January 2023. Data related to polysomnography-polygraphy (PSG) and serum levels of insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) were collected.ResultsThe mean age in the rhGH group was 20.76 ± 9.22 months, which was comparable to that of the non-rhGH group (25.23 ± 13.81 months). The demographic and anthropometric parameters were similar across the two groups after 52 weeks of treatment. Administration of rhGH to toddlers did not exert adverse effects on the obstructive apnea–hypopnea index (OAHI), central apnea index (CAI), oxygen desaturation index (ODI), mean percutaneous oxygen saturation (SpO2), lowest SpO2, duration when SpO2 is lower than 90%, or proportion of the patients with SpO2 lower than 90%. Furthermore, the increased IGF-1 z-score and IGFBP-3 level did not worsen SRBDs.ConclusionTreatment with rhGH for 52 weeks on young toddlers with PWS showed no deleterious effects on SRBDs. This shed more light on the importance of initiating rhGH therapy early in PWS patients.

Indications for genetic diagnosis in children with growth hormone deficiency and born small for gestational age.

The aim of the study is to analyze patients who do not respond adequately to human recombinant growth hormone (rhGH) treatment. Four boys were analyzed: three patients diagnosed with SNP at the ages of 1) 8 years and 2 months, 2)13years and 2 months, 3) 16 years and 6 months, and patient 4) at the age of 6 years and 11 months - born small for gestational age (SGA). They underwent rhGH treatment. The expected growth improvement was not observed in all boys. Patient 1 was diagnosed with aortic coarctation, and after each attempt to increase the rhGH dose, nocturnal vomiting occurred - epilepsy was diagnosed. Patient 2 had severe foot pain. Patient 3 had delayed puberty - hypogonadotropic hypogonadism was diagnosed. Patient 4 had dysmorphic features. Genetic tests revealed the following: 1) mixed gonadal dysgenesis - modifying treatment; 2) Fabry disease - enzyme treatment and rhGH improved growth; 3)Kallmann syndrome - discontinuing rhGH for testosterone supplementation; 4) KBG syndrome. 1. The presence of dysmorphic features and symptoms atypical for growth hormone deficiencies could warrant genetic diagnostics before initiating treatment. 2. Lack of significant improvement in growth is an indication for reevaluation of patients who have not completed growth. 3. Genetic studies in this patient group often elucidate the causes of slow growth rate. 4. The case authors have developed aproposal for amulticentre program aimed at establishing indications for genetic diagnosis in children diagnosed with SNP and SGA treated with rhGH.

Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature

To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.