Growth Hormone Therapy In Children Research Articles

Growth Hormone Therapy in a Child with Fetal Alcohol Syndrome: Personal Experience with Literature Review

Introduction: Fetal alcohol syndrome (FAS) is associated with a positive maternal history of drinking during pregnancy and the presence of characteristic dysmorphic features due to alcohol teratogenic effect. No evidence is yet available regarding the use of growth hormone (GH) for children with FAS for whom GH deficiency has not been confirmed. Case Presentation: We have highlighted an improvement in auxological parameters of a child with FAS and normal GH stimulation tests, using a GH dosage similar to that used in idiopathic GH deficit, without side effects. Conclusion: GH therapy in children with FAS may lead to an improvement in growth rate and an increase in final height, although, this condition is not included in the specific recommendations for use of GH. Prolonged follow-up and prospective studies are needed to evaluate long-term efficacy and monitor any possible onset of side effects.

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.

A Systematic Review of the Impact of Growth Hormone Therapy on Final Adult Height of Children with Idiopathic Short Stature

Abstract Introduction This review aims to systematically determine the effect of growth hormone (GH) therapy on adult height of children and adolescents with idiopathic short stature (ISS). Methods A systematic review was conducted to assess the effectiveness of GH therapy in children with ISS. Databases like ProQuest Central, journal @ Ovoid, EBSCOhost Medline Complete, Oxford University Press Journals, KB + JISC Collections Elsevier Science Direct Freedo, and BMJ, and cross-referencing of bibliographies were searched electronically. The randomized trials from 1989 to January 2023 were retrieved. Randomized trials with final adult height measurements and fit the inclusion criteria (height >2 standard deviation [SD] score below the mean with no comorbid conditions that would impair growth, peak growth hormone responses >10 μg/L, no previous history of GH therapy) were included in this review. The exclusion criteria are nonrandomized trials; trials include causes of short stature other than ISS, and studies include interventions other than GH and gonadotropin-releasing hormone analog (GnRH-a). A structured approach to the critical appraisal program by Oxford was used to analyze and extract the data. Results The study reviewed 14 eligible randomized trials, which recruited 2,206 assessable children for analysis. Seven trials compared different GH doses, four trials compared GH therapy with controls, and three trials compared a combination of GH and GnRH therapy with GH alone. Apart from one study, the overall dropout rate was not high. The high percentage of boys was a potential source of heterogeneity between trials. The change in height (HT)-SD score was 1.06 ± 0.30 and 0.18 ± 0.27 with treatment and control children, respectively, and the difference is statistically significant (p < 0.001). The overall mean height gain was 5 cm (0.84 SD score) more in treated children. The height velocity was found to be decreased significantly (p < 0.001) in the second and third years of treatment in the GH + GnRH-a treated group from 7 cm/year during the first year of treatment to 5.4 cm during the second year and 4.9 cm/year during the third year. They also found that using a higher dose of GH at 9 mg/m2/week leads to approximately 7 cm mean final height gain; however, lower dose regimens are less effective. Conclusion Although the magnitude of the effectiveness of GH therapy is, on average, less than that achieved in other conditions for which GH is licensed, GH therapy seems to be effective in children with idiopathic short stature, and it reduces the deficit in height as adults. Moreover, the effect seems to be dose-dependent, with better results at high GH doses, and the response variability is seen in different individuals. The use of combined GH with GnRH therapy needs to be balanced with their side effects.

Early psychomotor development and growth hormone therapy in children with Prader-Willi syndrome: a review.

Prader-Willi syndrome (PWS) is a rare genetic disorder caused by the loss of imprinted gene expression on the paternal chromosome 15q11-q13. PWS is characterized by varying degrees of early psychomotor developmental deficits, primarily in cognition, language, and motor development. This review summarizes the early mental cognitive development, language development, and motor development in patients with PWS, compares the correlation of genotype with phenotype, and provides an update regarding the effects and concerns related to potential main side effects of treatment with recombinant human growth hormone on early psycho-cognitive and motor function development along with the linear growth and body composition of children with PWS.Conclusion: Early psychomotor development is strongly correlated with the prognosis of patients with PWS; moreover, current studies support that the initiation of interventions at an early age can exert significant beneficial effects on enhancing the cognitive and linguistic development of patients with PWS and allow them to "catch up" with motor development. What is Known: • Prader-Willi syndrome is a rare genetic disorder characterized by multisystem damage, andchildren with Prader-Willi syndrome are typically characterized by early developmental delays, specifically in the areas of cognitive and motor development. •Recombinant human growth hormone therapy is the only medical treatment approved for Prader-Willi syndrome. What is New: •Extensive presentation of psycho-cognitive and motor development features and genotype-phenotype correlation in children with Prader-Willi syndrome. • The effects of growth hormone on early psychomotor development in children with Prader-Willi syndrome were thoroughly reviewed, including their short- and long-term outcomes and any associated adverse effects.

Growth hormone therapy for children with Duchenne muscular dystrophy and glucocorticoid induced short stature

ObjectiveTo evaluate the outcome of recombinant human Growth Hormone (rhGH) therapy in patients with Duchene Muscular Dystrophy (DMD) and glucocorticoid treatment with compromised growth. DesignFour DMD patients on Deflzacort 0.6–0.85 mg/kg/day or prednisolone 0.625 mg/kg/day recieved rhGH (0.24 mg/kg/week) for 6–18 months. Primary outcomes were Growth velocity and Height for age Z-scores (Height SD). ResultsGrowth velocity increased from 0 to 3.25 cm/year prior to GH therapy to 3.3–7.8 cm/year over a period of 6–18 months. The typical Height SD decline in DMD was reversed in two patients and blunted in one. No adverse events or deterioration in cardiac or respiratory parameters were associated with the rhGH treatment. ConclusionsrhGH appears to be safe and efficient in promoting growth of patients with glucocorticoid induced growth failure in DMD.

Real life long-term efficacy and safety of rhGH therapy in children with SHOX deficiency.

This Italian survey aims to evaluate real-life long-term efficacy and safety of rhGH therapy in children with short stature homeobox-containing gene deficiency disorders (SHOX-D) and to identify potential predictive factors influencing response to rhGH therapy. This is a national retrospective observational study collecting anamnestic, anthropometric, clinical, instrumental and therapeutic data in children and adolescents with a genetic confirmation of SHOX-D treated on rhGH. Data were collected at the beginning of rhGH therapy (T0), yearly during the first 4 years of rhGH therapy (T1, T2, T3, T4) and at near-final height (nFH) (T5), when available. 117 SHOX-D children started rhGH therapy (initial dose 0.23 ± 0.04 mg/kg/week) at a mean age of 8.67 ± 3.33years (74% prepubertal), 99 completed the 1st year of treatment, and 46 reached nFH. During rhGH therapy, growth velocity (GV) SDS and height (H) SDS improved significantly. Mean H SDS gain from T0 was +1.14±0.58 at T4 and +0.80 ± 0.98 at T5. Both patients carrying mutations involving intragenic SHOX region (group A) and ones with regulatory region defects (group B) experienced a similar beneficial therapeutic effect. The multiple regression analysis identified the age at the start of rhGH treatment (β -0.31, p = 0.030) and the GV during the first year of rhGH treatment (β 0.45, p = 0.008) as main independent predictor factors of height gain. During rhGH therapy, no adverse event of concern was reported. Our data confirm the efficacy and safety of rhGH therapy in SHOX-D children, regardless the wide variety of genotype.

Effect of Growth Hormone Therapy in Children with Isolated Growth Hormone Deficiency

The most frequent reason of short stature is Idiopathic short stature (ISS). If this condition is left untreated, the person's final height will be below the normal height range. Objective: To determine the efficacy of growth hormone treatment in short-stature children with isolated growth hormone deficiency. Methods: This was a retrospective cross-sectional study conducted in the department of Pediatric Endocrinology, Children Hospital, PIMS after approval from ethical review board. Epidemiological characteristics and response to therapies were noted and frequencies and Means were calculated. SPSS version 22 was used for statistical analysis. Results: Out of 87 study participants, there were 47 males and 40 female patients. The mean age was 10.04 + 1.89. The mean height and weight of study participants was 105.13 + 16.98cm and 21.55 + 7.63kg respectively. The mean isolated growth hormone value was noted as 5.40 + 1.43. The majority of the study participants were consanguineous i.e., 77%. Almost 48.3% study participants had growth hormone deficiency. The mean growth hormone velocity at 6th and 12th month was 6.52 + 2.08 and 7.89 + 2.54 respectively. In the end majority of the participants (82.8%) showed improvement. At 6th and 12th month both time points the results depicts a statistically significant difference among both groups (Improved Vs. Consistent) (p-value < 0.001). Conclusions: Recombinant growth hormone (GH) is an effective treatment for patients with GH deficiency to improve their growth. It was concluded that the children with ISS showed improvement after receiving GH therapy.

Association between uric acid and height during growth hormone therapy in children with idiopathic short stature.

Serum uric acid (UA) within appropriate levels is reported to be beneficial in patients with idiopathic short stature (ISS). This study aimed to evaluate the association between serum UA levels and height standard deviation scores (SDS) in patients with ISS during growth hormone (GH) therapy. A longitudinal study (LG Growth Study) of 182 children (mean age: 7.29±2.60 years) with ISS was performed. All participants were in the prepubertal stage and treated with GH, and the data within a treatment period of 30 months were analyzed. In the adjusted Pearson's correlation, UA was significantly correlated with height SDS after controlling for sex, age, and body mass index (BMI) SDS (r=0.22, p=0.007). In the adjusted multiple regression analyses, the height SDS was significantly associated with UA after controlling for sex, age, and BMI SDS (β=0.168, p=0.007). Within the 30-month treatment period, the UA levels significantly increased as the height SDS increased, and the mean UA levels at baseline and 30 months after treatment were 3.90±0.64 mg/dL and 4.71±0.77 mg/dL, respectively (p=0.007). In conclusion, UA is related to height SDS, and GH treatment leads to a significant increase in UA without hyperuricemia. Elevated UA is considered a favorable outcome of GH therapy, and further studies are needed to determine its role as a monitoring tool.

Metabolic and Cardiac Effects of Growth Hormone Therapy in Children with Turner Syndrome

Metabolic and Cardiac Effects of Growth Hormone Therapy in Children with Turner Syndrome

A Case Series Study on Growth Hormone Therapy in Children with Prader-Willi Syndrome in Portugal.

Prader-Willi syndrome is a multisystemic genetic disorder associated with shorter adult height. Nowadays, all paediatric Prader-Willi syndrome patients are considered for growth hormone treatment. We present the experience of this treatment at a Portuguese paediatric endocrinology unit and intend to emphasise the importance of creating a follow-up national network of these patients. Longitudinal, retrospective, analytical study of Prader-Willis syndrome patients using data between 1989 and 2021. Growth hormone therapy was offered to eligible patients. The analysis included all Prader-Willis syndrome patients, with a comparison between treated and untreated patients; a longitudinal analysis of patients receiving growth hormone therapy (baseline, 12 and 36 months of follow-up) was also carried out. The statistical analysis was carried out using STATA® v13.0. Out of 38 patients with Prader-William syndrome, 61% were male. The median age at diagnosis was four months and 61% received growth hormone therapy. The patients who reached adulthood, or 18 years old, had a median near-adult height, Z-score of -2.71, and their median body mass index indicated class 2 obesity, regardless of growth hormone therapy. Patients had a lower body mass index in the growth hormone group (35 vs 51 kg/m2, p < 0.042) near-adult height. This case series represents the first national study that included patients on growth hormone therapy after the National Health Service started supporting the treatment for Prader-Willi syndrome patients and supports its use, reinforcing the positive effects on growth and body mass index. Longer follow-up studies are needed to analyse the effect of growth hormone on patient metabolic profiling, body composition and cognitive level.

Adherence to Growth Hormone Therapy in Children with Primary Isolated Growth Hormone Deficiency

Background: Poor or non-adherence to growth hormone (GH) therapy is the most vital factor that could affect the growth potential of the individual. Aim: To assess the adherence and growth outcomes in growth hormone-deficient children treated with recombinant human growth hormone (r-hGH) via easypod™. Methods: The medical records of children with primary isolated GH deficiency and treated with r-hGH via easypod™ were retrospectively analyzed. The primary endpoint was to assess the mean rate of treatment adherence. Secondary endpoints were to study the changes in height, height standard deviation (SD) score, height velocity, and height velocity SD score after one-year of r-hGH treatment and the impact of adherence on the growth outcomes. Results: The mean age of the children included in this study was 10 years (age range: 8 to 11 years). Adherence to the r-hGH varied from 74-98% (mean 87%). Annular height velocity, the height SD score, and Insulin growth factor-1 level were 2 - 4 cm, -6.2 SD to -2.1 SD, and 22 to 218 ng/ml, respectively before initiation of the therapy, and reaches to 5 - 8 cm, -5.4 SD to -1.25 SD, and 85 to 545 ng/ml after one-year of r-hGH therapy. A good correlation between adherence and height was observed (r=0.85, p&lt;0.01). Conclusion: We found an acceptable adherence to r-hGH treatment among children with primary isolated GH deficiency. We also found a significant relationship between drug adherence and improved growth outcomes.

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

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

First Clinical Study on Long-Acting Growth Hormone Therapy in Children with Turner Sydrome.

Study on long-acting growth hormone (LAGH) therapy in Turner syndrome (TS) is a 2-year retrospective study including patients diagnosed with TS from 2018–2021. Patients were divided into four groups: Group 1 to 4 were low dose (0.1 mg/kg/ w), high-dose (0.2 mg/kg/w) LAGH, daily GH (0.38 mg/kg/w), and untreated control. The efficacy and safety data were analyzed. Seventy-five TS cases with the age 7.9±2.9 years and the bone age 6.8±2.8 years were recruited. In year 1: The change of height standard deviation score (ΔHtSDS) and height velocity (HV) in Group 2 were comparable to Group 3, both two groups were higher than Group 1. ΔHtSDS and HV in all GH treatment group were higher than untreated group. IGF1 increased in all treatment groups, only 4 cases had IGF1>3 SD. In year 2: ΔHtSDS and HV in Group 2 and 3 were comparable. Five cases had IGF1>3 SD. Correlation analysis for LAGH efficacy at year 1 indicated that baseline variables correlated with ΔHtSDS include: GH dose, CA (chronological age), and bone age (BA). The HV was positively correlated with baseline GH dose, HtSDS, IGF-1SDS and negatively correlated with baseline CA, BA, and BMI. No GH-related serious adverse effects were observed. The high-dose LAGH treatment in TS patients is effective and safe as daily GH for 2 years. The favorable prognosis factors include sufficient GH dose and early treatment. IGF1 monitoring and weight control are important.

Growth hormone (GH) deficiency and GH replacement therapy in patients previously treated for Cushing's disease.

Several complications associated with active Cushing's disease may persist even years after complete and successful therapeutic remission of hypercortisolism. Growth hormone deficiency (GHD) shares many clinical features seen in patients with Cushing's disease, and its presence after disease remission (GHD-CR) might negatively influence and potentially worsen the systemic complications caused by previous hypercortisolism. GHD-CR is more prevalent in women, and compared to other causes of GHD, patients are younger at the onset of the pituitary disease, at diagnosis of GHD-CR and at start of GH therapy; prevalence of pituitary macroadenomas and visual abnormalities are lower, while prevalence of diabetes, hypertension, low bone mass, fractures, and worst quality of life, are higher. Serum IGF-1 levels are not useful for the diagnosis of GHD-CR and the application of GH stimulating tests requires some special attention in addition to the general recommendations for detecting GHD from other etiologies. In patients with active hypercortisolism, GH secretion is completely suppressed, but it may spontaneously and progressively recover over the years following successful therapy, meaning that GH testing may be performed at an appropriate time after remission for the correct diagnosis. Moreover, if the patient presents concomitant adrenal insufficiency, GH testing should only be carried out under adequate cortisol replacement therapy. GH therapy in children with GHD-CR improves adult height in the majority of patients, while GH therapy in adults has been associated with improvements in body composition, lipid profile and quality of life, but also with worsening of glucose metabolism.

Compliance to Growth Hormone Therapy in Children and Adolescents with Growth Hormone Deficiency and Turner Syndrome and Impact on Height Velocity: A Prospective Study

Adherence to recombinant growth hormone (rGH) in children is necessary to ensure good treatment outcome. Reported non-compliance to rGH in children varied from 5-82% with little data involving Asian population. The objectives of this study are to evaluate the compliance of children and adolescents to rGH, effect of non-compliance on growth and factors affecting non-adherence. Methods: This is a prospective cohort study over 1-year aiming at all patients age less than 18 years old treated with rGH in our centre. Compliance was assessed from the number of returned medications and electronic record within device. Poor compliance was defined as utilised dose &lt;86% prescribed (equivalent to missing injection ≥1 per week). Result: Thirty-four patients were recruited including 20 (59%) patients with GH deficiency and 14 (41%) with Turner syndrome. Poor compliance was noted in 35% of patients. Poor compliance in GHD patients was significantly associated with an older age (mean 12.55 ± 3.33 vs 9.28 ± 3.20 years old, p=0.038) and longer duration of treatment (mean 5.41 ± 3.0 vs 2.93 ± 2.18 years, p=0.046). Frequent reasons for missing doses were forgetfulness and inadequate medications. Participants with poor compliance had significantly reduced height velocity (HV) and HV standard deviation score (SDS) compared to those with good compliance (p&lt;0.05). Conclusion: Poor compliance is more common in adolescents, those on longer duration of treatment and leads to significantly reduced height velocity. Regular monitoring throughout the course of rGH is important. Measures to improve compliance must address the underlying reasons.

Long-term effectiveness of growth hormone therapy in children born small for gestational age: An analysis of LG growth study data.

PurposeGrowth hormone (GH) treatment has been used to improve growth in short children who were born small for gestational age (SGA). The aim of this study was to investigate the long-term efficacy of GH treatment in these children.MethodsData from a multicenter observational clinical trial (ClinicalTrials.gov NCT01604395, LG growth study) were analyzed for growth outcome and prediction model in response to GH treatment. One hundred fifty-two children born SGA were included.ResultsThe mean age of patients born SGA was 7.13 ± 2.59 years. Height standard deviation score (SDS) in patients born SGA increased from -2.55 ± 0.49 before starting treatment to -1.13 ± 0.76 after 3 years of GH treatment. Of the 152 patients with SGA, 48 who remained prepubertal during treatment used model development. The equation describing the predicted height velocity during 1st year of GH treatment is as follows: the predictive height velocity (cm) = 10.95 + [1.12 x Height SDS at initial treatment (score)] + [0.03 x GH dose (ug/kg/day)] + [0.30 x TH SDS at initial treatment (score)] + [0.05 x age (year)] + [0.15 x Weight SDS at initial treatment (score)] ± 1.51 cm.ConclusionsGH treatment improved growth outcome in short children born SGA. We also developed a prediction model that is potentially useful in determining the optimal growth outcome for each child born SGA.Trial registrationClinicalTrials.gov Identifier: NCT01604395.

Management of Growth in Pediatric Chronic Renal Failure: A Narrative Review

Background: Growth impairment is a common problem in Chronic Kidney Disease (CKD) children. Approximately 40% of children with CKD have a reduced final height. Growth impairment affects school attendance, duration of hospitalization, adult height, and even risk of death. Objectives: Various studies have shown that patients with moderate to severe growth failure have higher mortality rates (three folds) than those with normal growth. This narrative review aimed to define the management of growth in pediatric chronic renal failure. Methods: This study was conducted through a literature search with the keywords of chronic renal failure, kidney transplant, Glomerular Filtration Rate (GFR) combined with growth, short stature, and growth hormone using PubMed, Scopus, Web of Sciences, Cochrane, and Embase databases. Results: Growth impairment in children with CKD occurs due to diverse etiologies, such as uremia, anemia, metabolic acidosis, etc. It becomes more prominent in GFR&lt;75 ml/min/1.73 m2. Growth hormone (GH) therapy seems to be a safe and effective therapeutic modality consequent to the correction of associated metabolic disturbances. Conclusions: This study indicated that pretransplant GH therapy in children with CKD and its temporary discontinuation at kidney transplantation up to one year after transplantation leads to improved growth velocity. Therefore, it seems that considering GH therapy in children with CKD is mandatory.

Recombinant growth hormone therapy in children with Turner Syndrome in Korea: a phase III Randomized Trial

BackgroundShort stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS.MethodsThis open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450–0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450–0.050 mg] /kg/day).ResultsThe change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (− 1.02) satisfied the non-inferiority margin (− 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups.ConclusionsThis study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future.Trial registrationThe study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013).

Recombinant growth hormone therapy for X-linked hypophosphatemia in children.

Conventional treatment of X-linked hypophosphatemia with oral phosphate and calcitriol can heal rickets, but it does not always raise serum phosphate concentrations significantly, nor does it always normalize linear growth. Some clinical trials suggest that combining recombinant human growth hormone therapy with conventional treatment improves growth velocity, phosphate retention, and bone mineral density, but some clinical trials suggest that it appears to aggravate the pre-existent disproportionate stature of such children. This is an updated version of a previously published review. To determine whether recombinant human growth hormone therapy for children with X-linked hypophosphatemia is associated with changes in longitudinal growth, mineral metabolism, endocrine function, renal function, bone mineral density, body proportions, and also with any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE and the reference lists of identified trials and other reviews. We also undertook some additional handsearching of relevant journals and conference proceedings. Date of the most recent search: 12 January 2021 SELECTION CRITERIA: All randomized controlled studies or quasi-randomized controlled studies comparing growth hormone (alone or combined with conventional treatment) with either placebo or conventional treatment alone in children with X-linked hypophosphatemia. Two authors independently assessed studies for risk of bias and extracted data from eligible studies. GRADE criteria were used to assess the certainty of the evidence for each outcome. We included two studies (20 participants) in the review. In one cross-over study, results showed that recombinant human growth hormone therapy may improve the height standard deviation (SDS) score (z score), but we are unsure whether the intervention was the reason behind a transient increase in serum phosphate and tubular maximum for phosphate reabsorption. In the second, parallel study, treatment may also have improved the height SDS from baseline in the rhGH group compared to the control group, although no significant difference was seen between groups after three years, MD 0.50 SDS (95 % CI -0.54 to 1.54) (low-certainty evidence). The treatment was possibly well-tolerated during both studies with only transient adverse effects seen in three participants (low-certainty evidence). We are uncertain whether growth hormone improves serum phosphate levels or change in TmP/GFR (very low-certainty evidence). The treatment may make little or no difference to alkaline phosphatase levels (low-certainty evidence). We do not have enough high-certainty evidence to recommend the use of recombinant human growth hormone therapy in children with X-linked hypophosphatemia.

Follow-Up Study of Growth Hormone Therapy in Children with Kabuki Syndrome: Two-Year Treatment Results

Introduction: Kabuki syndrome (KS) is a genetic disorder with characteristic facial dysmorphisms, short stature, hypertension, and obesity later in life. The aim of this study was to evaluate catch-up growth and cardiovascular markers before and during growth hormone (rhGH) treatment in KS children. Methods: This prospective study included 18 children whose KS was genetically established. Each KS subject received rhGH for a period of 2 years. Several measurements were performed before and during treatment: anthropometry, glucose metabolism, lipid profile, markers for endothelial function, and low-grade inflammation. Results: This study found an increase in delta height standard deviation score (SDS) for the whole group of 1.1 SDS after 2 years of rhGH treatment. Baseline metabolic profiles showed no cardiometabolic abnormalities in these children. Although 4 out of 18 children were obese, there were no signs of the metabolic syndrome. During rhGH treatment, serum low-density lipoprotein cholesterol concentrations decreased significantly (2.16–1.91 mmol/L, p = 0.04). Apolipoprotein B100 concentrations also showed a reduction after 24 months of treatment, but the other lipid and (apo)lipoprotein parameters did not change. While other endothelial function markers were stable, only vascular cell-adhesion molecule-1 concentrations increased (1,084–1,161 pg/mL, p < 0.01) during rhGH therapy. Furthermore, BMI and waist circumference improved during treatment. There were no signs of hypertension. Conclusions: At baseline and during rhGH therapy, there were no signs of the metabolic syndrome. This is the first study demonstrating that rhGH treatment in KS children is a safe and effective therapy and that it positively influences linear height without exerting adverse effects on a wide array of cardiovascular risk markers.