Growth Hormone In Children Research Articles

Growth with something other than growth hormone in children with craniopharyngioma

Growth with something other than growth hormone in children with craniopharyngioma

Therapeutic efficacy of recombinant human growth hormone in children with different etiologies of dwarfism from a pharmacoeconomic point of view.

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

Cerebral white matter hyperintensities in adults born small for gestational age at 12 years after cessation of childhood growth hormone treatment: a prospective cohort study including untreated controls

Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. Yet, previous studies lacked an appropriate control group which is a major limitation. We prospectively studied cerebral white matter hyperintensities (WMHs) in adults born SGA at 12 years after cessation of childhood GH-treatment (SGA-GH), compared to appropriate controls. In this prospective cohort study, performed between May 2016 and December 2020, total WMHs, periventricular WMHs (PVWMHs) and deep WMHs (DWMHs) were the primary outcomes of the study, they were qualitatively assessed using 3Tesla (T) Magnetic Resonance Imaging (MRI) and scored using the Fazekas scale in SGA-GH adults and in 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). Regression analyses were performed in the total cohort to evaluate the associations of GH-treatment and birth characteristics with WMHs. 297 adults were investigated (91 SGA-GH, 206 controls). Prevalence of total WMHs was 53.8% (95% CI 43.1-64.3) in SGA-GH, 40.5% (95% CI 25.6-56.7) in SGA-S, 73.9% (95% CI 61.9-83.7) in SGA-CU and 41.1% (95% CI 31.1-51.6) in AGA adults. No statistically significant differences in total WMHs, PVWMHs and DWMHs were found between SGA-GH compared to SGA-S and AGA adults. Highest prevalence of all type of WMHs was found in SGA-CU adults compared to all groups. Higher prevalence of total WMHs was associated with lower birth weight standard deviation score (SDS), but not with GH-treatment. Our findings suggest that GH-treatment in children born SGA has no negative impact on the prevalence of all type of WMHs at 12 years after GH cessation compared to appropriate controls. SGA-CU adults had the highest prevalence of all type of WMHs around age 30 years. Novo Nordisk.

Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial

ABSTRACT Objectives This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand. Methods According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment. Results The two intervention groups’ Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%). Conclusions The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles. Clinical trial registration www.IRCT.irIRCT20171122037571N1.

Update on the use of long-acting growth hormone in children.

After extensive research and many years of waiting, long-acting growth hormone (LAGH) formulations have finally become a reality in clinical practice and emerge as a potential solution to address the challenges of daily injections of recombinant human GH (rhGH). In this review, we present a brief history of the development of LAGH and provide a critical analysis of the existing literature on the five LAGH available and approved to date for treatment in children. In clinical trials, LAGH therapy has shown noninferiority compared with daily rhGH therapy in promoting linear growth in children with GH deficiency, with similar rates of adverse events. In the real world, many questions still need to be answered, such as whether a specific group of patients will benefit most from the weekly injection, whether compliance will be better compared with daily rhGH, whether long-term efficacy, monitoring and safety profile will be the same for the different LAGH compounds, and whether the cost-effectiveness will justify their use in different settings.

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.

THE EFFECT OF ROSE AROMATHERAPY (ROSA CENTIFOLIA) ON SLEEP DURATION FOR INFANTS AGED 0-28 DAYS AT PONCOWATI PUBLIC HEALTH CENTER LAMPUNG TENGAH IN 2022

ABSTRACT Approximately 75% of growth hormone in children is excreted during sleep. In Indonesia, quite a lot of babies have sleep problems, which is around 44.2% of babies experience sleep disorders such as frequently waking up at night, but more than 72% of parents consider sleep disturbances in infants not a problem or only consider it a small problem (Sekartini , 2012; Chandraini, 2021).Based on presurvey data by looking at data on baby sleep duration problems, which was carried out in 2 Puskesmas Kabupaten Lampung Tengah, namely at UPTD Puskesmas Bandar Jaya and UPTD Puskesmas Poncowati, it was found that 12 infants aged 0-28 days had problems sleeping at UPTD Puskesmas Bandar Jaya, while in In Poncowati Health Center, 20 babies aged 0-28 days had problems fulfilling the baby's sleep time, which was marked by fussy babies and crying, babies couldn't sleep if they weren't carried by their mothers.This study was to determine the effect of giving rose aromatherapy on the sleep duration of infants aged 0-28 days at Poncowati Health Center in Lampung Tengah in 2022.The research method was qualitative with questionnaire research instruments, thenumber of samples were 36 respondents (infants aged 0-28 days) taken by purposive sampling technique, data analysis using t test with a two group pretest posttest approach with control group design.Result of the study with an increase in the average quality of baby sleep after beinggiven rose aromatherapy (Rosa Centifolia) at the Poncowati Health Center, Lampung Tengah in 2022 was 33.33% higher than the average increase in infant sleep quality in the control group of 29.17%. From the t-test, the p value of 0.001 ˂ α (0.05) means that H0 is rejected and Ha is accepted, which means that there is an influence between the two variables.The conclusion is that there is an effect of giving rose aromatherapy on the sleepduration of infants aged 0-28 days. Therefore, it is suggested that this research can be an alternative to get good sleep quality for infants aged 0-28 days. Keywords : Infant, Rose Aromatherapy, Sleep Duration. Bibliography : (35) 2015-2021

Auxological and metabolic effects of long-term treatment with recombinant growth hormone in children born small for gestational age: a retrospective study.

Children born small for gestational age (SGA) not showing catch-up during the first two years of life reportedly show an impaired growth rate and adult height, as well as a worse metabolic outcome, mainly in terms of glycemic and lipid profile, compared to general population. In SGA children with short stature, treatment with recombinant growth hormone (GH) is currently recommended until adolescence; therefore, it may last long-term. The aim of the current study was to evaluate the auxological and metabolic effects and the safety of long-term recombinant GH treatment in SGA children. The study included 15 SGA children (5 F, 10 M; mean age: 6.78 yrs) treated with GH for at least 48 months. Growth and metabolic parameters, including glycemic and lipid profile, transaminases, and urycemia, were collected every six months. Compared to baseline, SGA children showed a significant improvement in height, weight, and growth rate after four yaers of treatment with GH (p ≤ 0.002), being already evident after six months of treatment (p < 0.001). Noteworthy, patients showed a constant, significant improvement in height throughout the treatment, as it was significantly higher at each follow-up compared to the previous one, until 42 months of treatment, except at 30 months of treatment (p < 0.001 T6VST12; p < 0.01 T12VST18, T18VST24; p < 0.05 T30VST36, T36VST42). Considering metabolic parameters, compared to baseline, a recurring increase in glycemia (p ≤ 0.028 vs T30, T36, and T48) and decrease in AST (p ≤ 0.035 vs T36, T42, and T48) and an occasional decrease in LDL cholesterol (p ≤ 0.04 vs T24 and T42) and triglycerides (p = 0.008 vs T18) and increase in urycemia (p = 0.034 vs T42). Considering safety profile, treatment was well tolerated, as the most frequently reported adverse event was poor compliance (20%); no hyperglycemia, hypercholesterolemia or hyperstransaminasemia occurred throughout the treatment, CONCLUSIONS: Long-term GH treatment showed to be effective in improving height and growth rate in SGA children, with a positive impact of metabolic profile and a safety profile, although glycemia should be carefully monitored over time.

Vitamin D and the growth hormone in Children with Short Stature: Review Article

Vitamin D and the growth hormone in Children with Short Stature: Review Article

Ambulatory blood pressure monitorisation in children with recombinant growth hormone treatment.

It is safe to use recombinant growth hormone in children. Studies have shown it to be effective and safe, except for a few side effects in the short and long term after treatment. The present study investigated the presence of hypertension in pediatric patients receiving growth hormone treatment using 24 h ambulatory blood pressure monitoring (ABPM). This study is a single-center, retrospective study. Eighty-four patients aged 5-16 years who received growth hormone treatment for at least 3months, who underwent 24 h ABPM were analyzed. They were compared with 67 patients who had no risk factors for hypertension. In the study, 84 rhGH-treated patients (45.2 % male, 54.8 % female) and 67 healthy control groups (49.3 % male, 50.7 % female) were analyzed. The mean age of the patient group was 10.83±2.85 years and the mean age of the healthy control group was 13.1±2.93 years. The diagnostic classification of the patients receiving treatment was as follows: 66.6 % (n=56) partial growth hormone deficiency, 22.6 % (n=19) growth hormone deficiency, 7.1 % (n=6) bioactive growth hormone, 2.3 % (n=2) idiopathic short stature, 1.1 % (n=1) low birth weight for gestational age (SGA). Body mass index was significantly lower in the treated group (p=0.013). The duration of treatment was 6.04±4.9months. Daytime diastolic blood pressure was significantly lower in the treated group (p=0.001). There was no correlation between BMI and ABPM parameters in the treatment group and the control group. The present study shows that growth hormone treatment is safe in terms of high blood pressure.

The real-world experience of long acting growth hormone in children with growth hormone deficiency

The real-world experience of long acting growth hormone in children with growth hormone deficiency

Identifying patient-related predictors of permanent growth hormone deficiency.

Isolated childhood growth hormone deficiency (GHD) can persist into adulthood, and re-testing at the transition period is needed to determine whether continued growth hormone therapy is indicated. Here, our objective was to identify predictors of permanent GHD. Retrospective single-centre study of patients with childhood-onset GHD who were re-tested after adult height attainment. Auxological, clinical, laboratory, and MRI data throughout follow-up were collected. We included 101 patients. At GH treatment initiation, age was 8.1 ± 0.4 years, height -2.25 ± 0.8, and BMI -0.27 ± 0.1 SDS. The 29 (28.7%) patients with persistent GHD had lower height SDS (-2.57 ± 0.1 vs. -2.11 ± 0.1, p<0.001) and mean GH peaks (8.4 ± 1.0 vs.13.2 ± 0.5 mIU/L, p<0.001) at GHD diagnosis; at adult height, they had lower IGF1 (232 ± 19.9 vs. 331 ± 9.1 ng/mL, p<0.001) and higher BMI SDS (-0.15 ± 0.27 vs. -0.73 ± 0.13, p<0.005). By multivariate analysis, the best predictive model included height and BMI SDS, both GH peaks, and MRI findings at diagnosis. Patients with height at diagnosis <-3 SDS had a 7.7 (95% IC 1.4-43.1, p=0.02) fold higher risk of persistent GHD after adjustment on BMI SDS. An abnormal pituitary region by MRI was the strongest single predictor (7.2 times, 95% CI 2.7-19.8) and after multivariate analysis adjustment for GH peaks and height SDS at diagnosis, the risk increased to 10.6 (1.8 - 61.3) times. Height <-3 SDS at GHD diagnosis and pituitary MRI abnormalities should lead to a high index of suspicion for persistent GHD.

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

Long-acting PEGylated growth hormone in children with idiopathic short stature

Long-acting PEGylated growth hormone in children with idiopathic short stature

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

Retracted: Effect of Vitamin D Combined with Recombinant Human Growth Hormone in Children with Growth Hormone Deficiency.

[This retracts the article DOI: 10.1155/2022/7461958.].

Diagnosis of childhood and adolescent growth hormone deficiency using transcriptomic data.

Gene expression (GE) data have shown promise as a novel tool to aid in the diagnosis of childhood growth hormone deficiency (GHD) when comparing GHD children to normal children. The aim of this study was to assess the utility of GE data in the diagnosis of GHD in childhood and adolescence using non-GHD short stature children as a control group. GE data was obtained from patients undergoing growth hormone stimulation testing. Data were taken for the 271 genes whose expression was utilized in our previous study. The synthetic minority oversampling technique was used to balance the dataset and a random forest algorithm applied to predict GHD status. 24 patients were recruited to the study and eight subsequently diagnosed with GHD. There were no significant differences in gender, age, auxology (height SDS, weight SDS, BMI SDS) or biochemistry (IGF-I SDS, IGFBP-3 SDS) between the GHD and non-GHD subjects. A random forest algorithm gave an AUC of 0.97 (95% CI 0.93 - 1.0) for the diagnosis of GHD. This study demonstrates highly accurate diagnosis of childhood GHD using a combination of GE data and random forest analysis.

Long-acting PEGylated growth hormone in children with idiopathic short stature: time to reconsider our diagnostic and treatment policy?

Idiopathic short stature (ISS) is a diagnosis of exclusion, and therefore each child with short stature or slow growth referred to a paediatrician deserves a full medical history and physical examination, as well as radiological and laboratory screening tests. In patients with an increased likelihood of a genetic cause, genetic testing is indicated. Idiopathic short stature is an approved indication for recombinant human growth hormone (rhGH) in the USA but not in most other parts of the world. In a recent article published in this journal, Luo et al reported on the 1-year's results of a multicentre randomized controlled trial (n = 360) on the efficacy and safety of two dosages of long-acting PEGylated rhGH (PEG-rhGH, Jintrolong®) (0.1 or 0.2 mg/kg body weight per week, respectively) in children with ISS compared with an untreated control group. The growth response to the higher dosage was similar to reported data on daily rhGH. In this commentary, we discuss whether the recent data on genetic causes of short stature in children who initially were labelled ISS, and data on the long-term safety of daily rhGH, may influence the balance between risks and benefits of rhGH treatment in children with ISS. We further discuss the pharmacokinetic and -dynamic profile of PEG-rhGH and its potential consequences for long-term safety.

Abstract 102

Treatment of short stature in children born small for gestational age (SGA) requires daily growth hormone (GH) injections that can be burdensome for patients and caregivers. Once-weekly somapacitan is a long-acting GH in phase 3 development for replacement therapy in children with GH deficiency. We report the 52-week results of the first phase 2, multinational, randomised, open-label, controlled, dose-finding trial (NCT03878446) investigating efficacy and safety of somapacitan as treatment for short stature in children born SGA compared with daily GH (Norditropin®, Novo Nordisk A/S). Sixty-two (62; 35.5% female) GH-treatment-naïve, prepubertal children received 0.16, 0.20 or 0.24 mg/kg/week subcutaneous (s.c.) somapacitan, or 0.035 or 0.067 mg/kg/day s.c. GH. All children were subsequently included in a long-term safety extension trial. At week 52, the observed mean height velocity (HV) was 8.5, 10.3 and 10.6 cm/year for 0.16 (n = 12), 0.20 (n = 13) and 0.24 mg/kg/week (n = 12) somapacitan, respectively, versus 9.4 and 11.2 cm/year for 0.035 (n = 11) and 0.067 mg/kg/day (n = 13) GH, respectively. The effect of the three somapacitan doses vs. GH on HV was not statistically significantly different. A similar pattern as seen for HV was observed for changes from baseline in height standard deviation score (SDS) and HV SDS. Dose-dependent increases in IGF-I SDS were observed with somapacitan and GH, and significant exposure-response relationships to HV were established for somapacitan. Among the somapacitan doses investigated, 0.24 mg/kg/week provided an IGF-I response most similar to that of 0.067 mg/kg/day GH. All somapacitan doses were well tolerated; no safety concerns were identified. Reported AEs were mild to moderate; most were evaluated as unlikely related to treatment by the investigator. The tolerability profile was favourable and consistent with that of GH. Low-titre non-neutralizing hGH anti-drug antibodies were detected in one child in the GH 0.067 mg/kg/day arm; none were detected in other treatment arms. One patient treated with somapacitan 0.20 mg/kg/week developed type 1 diabetes mellitus. This event was evaluated as not related to the treatment. Otherwise, there were no clinically relevant findings with respect to glucose metabolism. In conclusion, these data support that 0.24 mg/kg/week somapacitan appears most efficacious of the somapacitan doses investigated in short children born SGA after 52 weeks of treatment. Furthermore, the safety and tolerability profiles of this dose are similar to those of 0.067 mg/kg/day GH.

Osteometabolic profile and bone mass in the transition phase: ethnic differences in Brazilians treated with somatropin during childhood

ObjectiveThe main growth hormone action is to promote linear growth increasing protein synthesis stimulation and osteoblastic activity. Peak bone mass extends from adolescence to 30 years of age. Several factors may influence this acquisition and prevent fracture risk in adulthood, such as genetic potential, GH, ethnicity, and lifestyle factors. This study aims to compare bone mass and osteometabolic profile of white and Afro-descendant Brazilian adolescents in the transition phase, who were treated with human recombinant growth hormone in childhood. MethodsThe authors selected 38 adolescents from the Transition Outpatient Clinic of the University of São Paulo. Lumbar spine and total body bone mineral density (BMD) and bone mineral content (BMC), serum calcium, 25-OH-vitamin D and bone markers were analyzed at the rhGH withdrawal. ResultsThe mean age was 16.8 ± 1.6 years. There were 21 Afro-descendant and 17 whites. Thirty-four percent of the sample presented vitamin D insufficiency, 66% inadequate calcium intake and 44.7% physical inactivity. The Afro-descendants showed a lower lumbar spine and total body Z scores than those of the whites (p = 0.04 and p = 0.03, respectively), as well as their mean body weight (p = 0.03). There were no differences in the remaining osteometabolic parameters. ConclusionAs most adolescents had vitamin D insufficiency, low calcium intake, and physical inactivity, calcium, and cholecalciferol supplementation and lifestyle changes should be encouraged. The Brazilian Afro-descendant may be a vulnerable group for low bone mass, requiring special strategies to increase bone accrual and body weight. More studies are necessary to compare ethnic differences in this population.