rhGH Dose Research Articles

The role of IGF1 in determining body composition in children and adolescents with growth hormone deficiency and those with idiopathic short stature.

Treatment with recombinant human growth hormone (rhGH) increases insulin growth factor-1 (IGF1) levels, therefore, monitoring both IGF1 and growth constitutes an acceptable parameter of therapeutic safety and efficacy. We aimed to investigate the relationship between IGF1 level and body composition in children and adolescents undergoing rhGH therapy for growth hormone deficiency (GHD) and idiopathic short stature (ISS). This observational retrospective study included the bioimpedance analysis (BIA) reports (n = 305) of 135 pediatric patients (age 5-18 years), 64 with GHD and 71 with ISS, conducted as part of routine clinic visits. Sociodemographic and clinical data were extracted from medical records. Generalized estimating equations linear models were used to explore the contributing factors for body composition components of fat percentage (FATP), appendicular skeletal muscle mass (ASMM) z-score, and muscle-to-fat ratio (MFR) z-score while adjusting for cumulative doses of rhGH. Subjects with GHD exhibited higher body mass index z-scores (p < 0.001), higher FATP and truncal FATP scores, lower MFR z-score, and higher diastolic blood pressure percentiles than the ISS group (p = 0.010, p = 0.027, p = 0.050, and p = 0.050, respectively). Female sex (p < 0.001) and a GHD diagnosis (p < 0.001), were major contributors to higher FATP scores; female sex (p = 0.049) and ISS diagnosis (p = 0.005) were major contributors to higher MFR z-scores; and female sex (p < 0.001), older age (p < 0.001) and higher insulin-like growth factor 1 z-scores (p = 0.021) were major contributors to higher ASMM z-scores. Socioeconomic position and cumulative rhGH dose were not significant contributors to body composition parameters. Children with GHD, including those undergoing rhGH treatment, may be at risk for increased adiposity and associated metabolic implications. Sex- and age-adjusted IGF1 levels were related to muscle mass but not to adiposity. Hence, rhGH treatment aimed at increasing IGF1 levels may alleviate these effects by promoting muscle growth.

Recombinant human growth hormone promotes wound angiogenesis in burned mice through the ERK signaling pathway.

Burns are the most severe type of trauma, and the resulting ischemia and hypoxia damage can promote the dysfunction and even failure of tissues and organs throughout the body, endangering patients' life safety. Recombinant human growth hormone (rhGH) has the functions of promoting protein synthesis to reverse negative nitrogen balance, accelerating wound healing, and improving immune function, which is widely used in the treatment of burns. However, the exact mechanism and pathway of rhGH's action is not yet fully understood. In this study, we observed the wound repair effect of recombinant human growth hormone (rhGH) on burned mice and further analyzed the mechanism of action, which can provide more comprehensive reference opinions for clinical practice. First, by establishing a burn mouse model and and intervening with different doses of rhGH, we found that the wound healing capacity of mice was significantly enhanced and the inflammatory and oxidative stress responses were obviously alleviated, confirming the excellent promotion of wound repair and anti-inflammatory and antioxidant effects of rhGH. Subsequently, we found that the expression of p-ERK1/2/ERK1/2, EGF, TGF-β, and VEGF proteins was elevated in the traumatic tissues of mice after rhGH intervention, suggesting that the pathway of action of rhGH might be related to the activation of ERK pathway to promote the regeneration of traumatic capillaries.

Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study.

The effect of recombinant human growth hormone (rhGH) on sleep-disordered breathing (SDB) in Malaysian children with Prader-Willi syndrome (PWS) is under-investigated. We determined (1) the short- and long-term effects of rhGH and (2) factors associated with worsening SDB in children with PWS receiving rhGH. This retrospective study included children with PWS (with and without rhGH) who had undergone at least 1 polysomnography. Outcomes measured were the presence of SDB before and after starting rhGH and the progress of SDB with and without rhGH. Serial insulin-like growth factor 1 (IGF-1) measurements were recorded. One-hundred and thirteen polysomnograms were analyzed. The majority (92.3%) of initial polysomnograms showed SDB, with a median (interquartile range) apnea-hypopnea index of 5.0 (2.6, 16.3) events/h. The age for receiving rhGH was a median (IQR) of 1.9 (0.7, 3.4) years. One-third (36.8%) had worsening SDB after initiating rhGH, which was associated with higher IGF-1 levels post-rhGH (P = .007). After a median of 5 years of rhGH, 73.6% maintained or reduced their positive airway pressure settings. Without rhGH, 80% had increased their positive airway pressure settings. Worsening SDB while on rhGH was associated with higher body mass index, lower rhGH dose, higher IGF-1 levels, and non-15q deletion. The majority of Malaysian children with PWS had SDB. At initiation of rhGH, one-third of patients had worsening SDB, associated with increased IGF-1 levels. Stabilization of SDB was more frequently seen in those receiving long-term rhGH. Worsening SDB while on rhGH was associated with a higher body mass index, receiving a lower dose of rhGH, higher IGF-1 levels, and non-15q deletion. Tan YT, Azanan MS, Hng SY, etal. Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study. J Clin Sleep Med. 2024;20(8):1291-1299.

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.

Primary response in GHD children treatment as apredictor for long-term therapy effectiveness therapy effectiveness.

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

Does excessive body mass affect the rhGH therapy outcomes in GHD children?

For 35 years, recombinant human growth hormone (rhGH) has been successfully used worldwide to treat children with short stature related to growth hormone deficiency (GHD). Growth hormone therapy requires an individual approach to the patient due to varying responses to the treatment. Excessive body weight is one of the factors influencing the response. To evaluate the impact of excessive body mass on rhGH therapy effectiveness in GHD children. 165 short-statured children with isolated GHD (mean age 10.72 ±3.33 years), treated with rhGH for at least one year (mean follow-up 4.32 ±1.80 years), were separated into 3 groups based on their BMI standard deviation score (SDS). Bone age, height, weight, insulin-like growth factor 1 level, and rhGH dose were obtained up to 10 years with one-year intervals. The mean change in height SDS in the first year was 0.52 ±0.41 SD and 0.60 ±0.32 SD for normal and excessive body weight children, respectively. The mean height velocity, based on the height SDS measured over the consecutive 5 years, was 0.44±0.25 SD/year for the normal-weight group and 0.32 ±0.24 SD/year for the excessive body weight group (p<0.1). Excess body weight has asignificant impact on rhGH therapy outcomes. This correlates with the height increase in the first year of observation; however, long-term observation has shown that children diagnosed with overweight or obesity achieve significantly worse results compared to their normal-weight peers.

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.

Response to growth hormone therapy in ring chromosome 15: Review and evidence from a new case on possible beneficial effect in neurodevelopment

Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15. Subject and methodWe tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized. ResultsTwelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was −5.1(−5.9/−4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year). ConclusionGH seems to be effective for r(15) syndrome patients with short stature.

Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland

The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values &gt; 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p &lt; 0.001. After 24 months of treatment, the values were: 47 (33%) &gt; 97th percentile by local vs. 6 (4.2%) by population standards; p &lt; 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 &gt; 97th percentile according to the local reference ranges and five (13%) &gt; 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.

Growth response of syndromic versus non-syndromic children born small for gestational age (SGA) to growth hormone therapy: a Belgian study.

A substantial proportion of SGA patients present with a syndrome underlying their growth restriction. Most SGA cohorts comprise both syndromic and non-syndromic patients impeding delineation of the recombinant human growth hormone (rhGH) response. We present a detailed characterization of a SGA cohort and analyze rhGH response based on adult height (AH). Clinical and auxological data of SGA patients treated with rhGH, who had reached AH, were retrieved from BELGROW, a national database of all rhGH treated patients held by BESPEED (BElgian Society for PEdiatric Endocrinology and Diabetology). SGA patients were categorized in syndromic or non-syndromic patients. 272 patients were included, 42 classified as syndromic (most frequent diagnosis (n=6): fetal alcohol syndrome and Silver-Russell syndrome). Compared with non-syndromic patients, syndromic were younger [years (median (P10/P90)] 7.43 (4.3/12.37) vs 10.21 (5.43/14.03), p=0.0005), shorter (height SDS -3.39 (-5.6/-2.62) vs -3.07 (-3.74/-2.62), p=0.0253) and thinner (BMI -1.70 (-3.67/0.04) vs -1.14 (-2.47/0.27) SDS, p=0.0054) at start of rhGH treatment. First year rhGH response was comparable (delta height SDS +0.54 (0.24/0.94) vs +0.56 (0.26/0.92), p=0.94). Growth pattern differed with syndromic patients having a higher prepubertal (SDS +1.26 vs +0.83, p=0.0048), but a lower pubertal height gain compared to the non-syndromic group (SDS -0.28 vs 0.44, p=0.0001). Mean rhGH dose was higher in syndromic SGA patients (mg/kg body weight/day 0.047 (0.039/0.064) vs 0.043 (0.035/0.056), p=0.0042). AH SDS was lower in syndromic SGA patients (-2.59 (-4.99/-1.57) vs -2.32 (-3.3/-1.2), p=0.0107). The majority in both groups remained short (<-2 SDS: syndromic 71%, non-syndromic 63%). Total height gain was comparable in both groups (delta height SDS +0.76 (-0.70/1.48) vs +0.86 (-0.12/1.86), p=0.41). Compared to non-syndromic SGA patients, syndromic SGA patients were shorter when starting rhGH therapy, started rhGH therapy earlier, and received a higher dose of rhGH. At AH, syndromic SGA patients were shorter than non-syndromic ones, but their height gain under rhGH therapy was comparable.

An Observational Study on Response to Growth Hormone Therapy in Indian Patients of Short Stature with Special Emphasis on Biochemical Parameters and Bone Biomarkers.

There is a lack of Indian data on short stature treatment using recombinant human growth hormone (rhGH). We explored the effects of such treatment in eastern Indian patients, with emphasis on biochemical parameters and bone biomarkers in addition to basic anthropometry. Our descriptive study covered 50 short stature patients of varied aetiology attending endocrine outpatient department (OPD) of a tertiary care teaching hospital. Patients were followed up for 1 year after the index visit, and prospective data were reconciled with past medical records. A dose of rhGH used was 0.18-0.375 mg/kg as standard, starting dose mostly being 0.2 mg/kg. Dosing was adjusted if the physician judged the clinical outcome to be less favourable than expected. Anthropometric parameters (height, weight, body mass index (BMI) and skeletal age) were recorded clinically, and various biochemical parameters and bone biomarkers were estimated from blood. Among 50 subjects, 60% had idiopathic growth hormone (GH) deficiency and 26% had Turner's syndrome. The median age at treatment start was 10 years, and the median treatment duration was 25.5 months. The height increased more in the first year of therapy. In the last 6 months, the height velocity was approximately 0.5 cm/month. Although the weight increased significantly, the increment slowed down in the last 6 months. Both remained less than age- and gender-matched references throughout. The skeletal age was on average 2 years behind chronological age (CA)-being 8.7, 9.6 and 11.3 years, respectively, at therapy start, after one year and at study end. Fasting blood glucose (FBG), total cholesterol and calcium level changes were not statistically significant. Serum cortisol and phosphate showed a modest but statistically significant rise, while thyroid-stimulating hormone (TSH) level declined. Insulin-like growth factor 1 (IGF-1) increase was relatively pronounced. Among bone biomarkers, a decrease in CTx and an increase in vitamin D were significant. Dual-energy X-ray absorptiometry (DEXA) data indicated that bone mineral density was less than that of age-matched controls despite treatment. The therapy was well tolerated. rhGH treatment leads to significant improvement in anthropometry in Indian children comparable with Western data. Bone biomarker changes indicate decreased bone resorption and increased bone formation although bone mineral density still lags behind age-matched controls.

GH Responsiveness Is not Correlated to IGF1 P2 Promoter Methylation in Children With Turner Syndrome, GHD and SGA Short Stature.

BackgroundThe methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed.ObjectiveThis study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied.DesignThis was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples.ResultsBasal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment.ConclusionsThis study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted.

LGG-40. Growth hormone replacement in children on therapy with Vemurafenib for Low Grade Glioma

BRAF inhibitors (iBRAF) are a therapeutical option for pediatric Low-Grade-Gliomas (pLGG), but their chronic use may be needed to prevent tumor regrowth. Growth hormone (GH) replacement in children with GH deficiency (GHD) and on oncological treatment is under debate. We report on our experience of recombinant human GH (rhGH) replacement in two children (1 Female, 1 Male) which started Vemurafenib therapy, at 5 (F) and 9,25 (M) years of age, for recurrent/progressive chiasmatic-hypothalamic pLGG, with partial response (RANO criteria) and subsequent stable disease. A diagnosis of GHD was established at 9,2 (F) and 11,2 (M) years of age (GH peaks to stimulation tests <3mcg/L), 4,2 (F) and 1,9 (M) years after Vemurafenib start. Both patients were treated with GnRH analogues for precocious puberty. rhGH dose was titrated to 0.020 mg/kg/day during follow-up based on IGF-1 levels < +2 SDS. Height remained stable in both (F: -3,4SDS; M: 0SDS), with a mean growth velocity after 2 years around 6 cm/yr. BMI increased in the F (1,59 to 1,78 SDS) and decreased in the M (2,66 to 2,56 SDS); Dual-X-ray absorbiometry confirmed high fat mass at T0 (F:54,6%; M:48%) and at T24 (F:49,2%; M:48,1%). Lipid profile improved in both patients (F: Triglycerides 175 to 152 mg/dl, LDL 195 to 155 mg/dl; M: Triglycerides 138 to 118 mg/dl, LDL 147 to 147 mg/dl, at T0 and T24, respectively), while baseline blood glucose increased (F: 83 to 96 mg/dl; M 82 to 91 mg/dl). Residual tumor was stable in both patients. CONCLUSIONS: In 2 GHD patients due to pLGG and treated with Vemurafenib, two-years of low-dose rhGH showed beneficial effects on height stabilization and on lipid profile, and a different impact on body composition parameters; rhGH was safe and not associated with residual tumor growth.

Response to Treatment with Recombinant Human Growth Hormone (rhGH) of Short Stature Children Born Too Small for Gestational Age (SGA) in Selected Centres in Poland.

Short stature resulting from SGA is an obligatory indication for treatment with rhGH. The aim of the study was to assess the response to rhGH treatment in patients treated in the years 2016–2020 in six clinical centers in Poland. During the analysis, auxological data were collected, and anthropometrical parameters (Ht, SDS Ht, HV and ΔHV) were reassessed. Subgroups of patients with dysmorphic features (DYSM), fetal alcohol syndrome (FAS) and Silver-Russel syndrome (SRS) were selected. The study group consisted of 235 children (137 boys). The medium initial age was 9.08 years, and 190 patients were in the prepubertal stage. The poor response to treatment was defined as ΔHt SDS < 0.3 and/or ΔHV < 3 cm/year. Seventeen per cent of all patients after the first year and 44% after the second year met the ΔHt SDS < 0.3 criterion, and 56% during the first and 73% during the second year met the ΔHV < 3 cm/year criterion. Our data suggest that patients with SRS may show the best response to treatment, which was sustained throughout the follow-up period. The best response in all subgroups was observed during the first 12 months of therapy. Although the proportion of patients meeting the poor response criteria was high, only a few patients exceeded the 97th percentile for IGF-1 concentration during the first year of treatment. This might suggest that increasing the dose of rhGH in the second treatment year in order to sustain accelerated HV would be safe in these patients.

Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model.

We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. We enrolled 1051 patients. Pre-treatment height was -2.43 SDS, lower than parental height (THt) (-1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was -1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the patients were shorter than -2 SDS from THt. The rhGH dose at nFHt was 0.19 mg/kg/week, lower than at the start (p < 0.001). The polynomial regression showed that nFHt was affected by gender, THt, age at puberty, height at puberty, age at the end of treatment (F = 325.37, p < 0.0001, R2 87.2%). This large national study shows that GHD children can reach their THt. The rhGH/kg/day dose significantly decreased from the start to the end of the treatment. Our model suggests the importance of a timely diagnosis, possibly before puberty, the beneficial effect of long-term treatment with rhGH, and the key-role of THt. Our prediction model has a very acceptable error compared to the majority of other published studies.

Therapeutic potential of a combination of recombinant human growth hormone (r-hGH) and vitamin D in children with idiopathic short stature

Purpose: To study the effectiveness and clinical significance of recombinant human growth hormone (rhGH) in combination with vitamin D in the treatment of idiopathic short-stature children.Methods: A total of 90 idiopathic short-stature children admitted at Children Health Care Center of Shiyan Maternal and Child Health Care Hospital, Shiyan between March 2017 and March 2020 were assigned to three groups: A, B and C, based on dose of r-hGH given. Group A received r-hGH at a dose of 0.26 mg/kg/week, while groups B and C received r-hGH at doses of 0.35 and 0.42mg/kg/week, respectively. All the patients were given vitamin D along with the r-hGH doses administered. Height, growth rate, bone age, height standard deviation score, fasting blood glucose, thyroid function and treatment effectiveness were determined and compared among the three groups before treatment, and one year after treatment.Results: Significantly higher height standard deviation score, growth rate, bone age, and height were observed in the three groups of patients after one year of treatment than before treatment, with group A &lt; group B &lt; group C (p &lt; 0.05). Fasting blood glucose and thyroid function were not significantly different amongst the three groups after treatment (p &lt; 0.05). Group C showed the highest treatment effectiveness, followed by group B, and then group A (p &lt; 0.05).Conclusion: The use of a combination of r-hGH and vitamin D produces a favorable treatment effectiveness in idiopathic short-stature children. However, further clinical trials are required to validate this treatment strategy.

Association Between Recombinant Growth Hormone Therapy and All-Cause Mortality and Cancer Risk in Childhood: Systematic Review and Meta-Analysis.

ObjectivesThe safety of recombinant human growth hormone (rhGH) treatment in childhood and the role of rhGH therapy in promoting tumorigenesis and progression have been the subject of debate for decades. We aimed to systematically assess the relationship between rhGH therapy in children and adolescents and clinical outcomes, including all-cause mortality, cancer mortality, cancer incidence, and risk of the second neoplasm.MethodsLiterature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates are expressed as standardized mortality ratios (SMRs), standardized incidence ratio (SIR), and relative risk (RR) with a 95% CI.ResultsData from 24 articles, involving 254,776 persons, were meta-analyzed. Overall analyses revealed the association of rhGH therapy was not statistically significant with all-cause mortality (SMR = 1.28; 95% CI: 0.58–2.84; P = 0.547; I2 = 99.2%; Tau2 = 2.154) and cancer mortality (SMR = 2.59; 95% CI: 0.55–12.09; P = 0.228; I2 = 96.7%; Tau2 = 2.361) and also cancer incidence (SIR = 1.54; 95% CI: 0.68–3.47; P = 0.229; I2 = 97.5%; Tau2 = 2.287), yet statistical significance was observed for second neoplasm (RR = 1.77; 95% CI: 1.33–2.35; P = 0.001; I2 = 26.7%; Tau2 = 0.055). Differences in the geographic region, gender, treatment duration, mean rhGH dose, overall rhGH exposure dose, and initial disease accounted for heterogeneity in the subgroup analyses.ConclusionOur findings indicate that the rhGH therapy is not related to all-cause mortality and cancer mortality and cancer incidence, yet it seems to trigger a second tumor risk. Future prospective studies are needed to confirm our findings and answer the more challenging question regarding the optimal dose of rhGH therapy in children and adolescents.

A Real-World Study of Recombinant Human Growth Hormone in the Treatment of Idiopathic Short Stature and Growth Hormone Deficiency.

ObjectiveThis study aimed to evaluate the clinical efficacy of recombinant human growth hormone (rhGH) in the treatment of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) and to explore the related factors affecting treatment efficacy.MethodsThe current research reflects a real-world study. A total of 79 patients with ISS and 95 patients with GHD (both groups pre-puberty) who had been treated with rhGH for more than one year from January 2010 to September 2019 were included in this study. The patients were divided into two groups, ie, an ISS and a GHD group, respectively. The growth indexes, such as chronological age (CA), bone age (BA), height standard deviation score (HtSDS), insulin-like growth factor-1 (IGF-1) SDS, and body mass index were recorded and compared between the two groups before and after treatment. The treatment efficacy was evaluated according to changes in HtSDS before and after treatment, and the influencing factors of clinical efficacy were analyzed using a multivariate regression model.ResultsAt the start of treatment, the differences in CA, BA, height, weight, sexual development stage, HtSDS, mid-parental height SDS, and IGF-1 SDS between the two groups were not statistically significant (P > 0.05). However, the initial dose of rhGH in the GHD group was significantly lower than in the ISS group (P < 0.001). Following rhGH treatment, the differences in CA, BA, BA/CA ratio, and IGF-1 SDS measured at 6, 12, 18, and 24 months between the ISS and GHD groups were not statistically significant, while the difference in HtSDS measured at 6 months was statistically significant. With the extension of rhGH treatment time, the annual growth rate (GV) gradually decreased, and the difference between HtSDS and the baseline gradually increased; however, the differences between the ISS and GHD groups were not statistically significant. The most important factor affecting the treatment efficacy for patients with ISS was age at the start of treatment; the most important factors affecting the treatment efficacy for patients with GHD were age and IGF-1 SDS.ConclusionRecombinant human growth hormone treatment can significantly improve the height of patients with ISS and GHD. There was no significant difference in growth rate between patients with ISS and those with GHD at relatively high doses. The common factor affecting the treatment efficacy of the two groups was the age at the start of treatment. During treatment, monitored data indicated that rhGH treatment of GHD and ISS thyroid function showed a clinical phenomenon in the form of increased free triiodothyronine, rather than hypothyroidism, which was rarely reported in existing studies.

Yearly Height Gain Is Dependent on the Truly Received Dose of Growth Hormone and the Duration of Periods of Poor Adherence: Practical Lessons From the French Easypod™ Connect Multicenter Observational Study.

ObjectiveTo study the impact of the true mean daily dose and the true mean number of injections per week on the yearly height gain in short children treated with recombinant human growth hormone (rhGH).Design and Methods220 children from the French Easypod™ Connect Observational Study (ECOS) used the Easypod™ electronic device to record rhGH injections. The mean daily rhGH dose (the sum of the doses truly received divided by the number of days) and mean number of injections per week (the number of injections truly performed divided by the number of weeks) were calculated. Linear mixed models were used to study the impact of short (3-month) and long (1-year) variations in rhGH administration on the yearly height change [as a standard deviation score (SDS)], with time on treatment as a covariate. For each patient, several periods of 3 or 12 months were considered and designated as poorly adherence or fully adherence. We studied the impact of each of period on the height change.ResultsAt treatment initiation, the mean ± SD age was 9.8 ± 3.7 years (females: 47%, prepubertal: 86%) and the mean height was -2.28 ± 0.92 SDS. The mean treatment duration was 3.2 ± 1.1 years (685.2 patient years). 122 patients were GH-deficient, 79 were small for gestational age, and 19 had Turner syndrome. When treatment was computed over 12-month periods, receiving a mean daily dose <0.03 mg/kg.d was associated with a 20% lower mean yearly height gain SDS when<3 injections/week were received (vs.>5 injections/week), whereas maintaining a mean daily dose >0.03 mg/kg.d with<3 injections/week was not associated with a lower yearly height gain SDS (vs.>5 injections/week). For 3-month periods, changes in the daily rhGH dose or the number of injections per week over such short period did not influence the yearly height gain SDS.ConclusionThe 12-month treatment model showed that when poor adherence leads to a low true daily GH dose, the yearly height gain is low. The 3-month treatment model showed that poor adherence for short periods (<3 months) had no impact on the height SDS.

Effects of high-dose recombinant human growth hormone treatment on IGF-1 and IGFBP-3 levels in idiopathic dwarfism patients.

Objective:To investigate the effects of high-dose recombinant human growth hormone(rhGH) treatment on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in patients with idiopathic dwarfism.Methods:This study retrospectively investigated records of idiopathic dwarfism patients treated at Anhui Children’s Hospital or the Affiliated Hospital of Xuzhou Medical University between May 2019 and October 2020. The study identified 76 patients, which were divided based on rhGH treatment dosage into high- and low-dose groups.Results:The high-dose group showed a total efficacy of 95.3%, which was significantly higher than the 79.41% observed in the low-dose group (P<0.05). Moreover, height, weight, IGF-1 levels, and IGFBP-3 levels were all significantly elevated in the high-dose group compared to the low-dose group (P<0.05). No significant difference in adverse reaction incidence was observed between high- (9.5%) and low-dose (8.8%) groups (P>0.05).Conclusions:Higher doses of rhGH can provide improved curative effects in patients with idiopathic short stature, likely via elevated levels of IGF-1 and IGFBP-3.