Duration Of Growth Hormone Therapy Research Articles

Adherence to Growth Hormone Treatment in Children During COVID-19 Pandemic

Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the COVID-19 pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. This was a multicenter survey study that was sent to pediatric endocrinologists in pandemic period (June 2021-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, and missed dose data and the causes in the recent year (after the onset of the pandemic) were queried. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% nonadherence). The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 mcg/kg, the annual growth rate was 1.15 SDS (min -2.74, max 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for nonadherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Nonadherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as nonadherence rate increased. During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

Evaluation of the response to growth hormone therapy when the decision of treatment was done based on the relation to the mid parental height

Introduction Midparental height (MPH) can be used as a crude prediction of the child’s adult height. Familial short stature (FSS) is a condition in which the final adult height achieved is less than the third percentile for the patient’s age, sex, and population. Nevertheless, it is consistent with parental height in the absence of nutritional, hormonal, acquired, genetic, and iatrogenic causes. The rationale for treating childhood short stature includes increasing height and alleviating psychosocial disability while maintaining favorable risk/benefit and cost/benefit ratios. Selection among management options may therefore depend on the degree to which each meets these goals. Inappropriately, ascribing a child’s extreme shortness to relatively short parents could thus result in delayed investigations or failure to appreciate the seriousness of a child’s situation.Aim The aim of this study is to evaluate the response to growth hormone (GH) therapy when the decision of treatment was made based on their relation to MPH whether FSS or much shorter than their MPH standard deviation score (SDS).Patients and methods This is a retrospective study; we studied the auxologic data of 21 children with FSS [height SDS (HtSDS) <−2, MPHSDS <−2 SD] and 14 children who were not short [HtSDS >−2, but ≥1 SD shorter than their MPHSDS who were treated with recombinant GH (somatropin/norditropin] 0.03–0.05 mg/kg/day daily for more than 1 year, and the dose was adjusted to keep the insulin-like growth factor-1 (IGF-1) level in the upper quartile of normal for age.Results In the FSS group, after an average of 3.27 years on GH treatment, the HtSDS increased by 0.92 SD, and IGF-1 SD increased by 2.87 SD. Difference between the HtSDS and MPHSDS improved significantly from −0.18 to 0.74 SD. In the other group, after GH therapy the HtSDS increased by 0.5 and IGFSDS increased by 3.24 SD. Difference between the HtSDS and MPHSDS improved significantly from −1.26 to −0.72 SD. However, the HtSDS was still more than 0.5 or more lower than the MPHSDS. In both groups, the HtSDS gain was positively correlated with the duration of GH therapy (r=0.52, P=0.01) and negatively correlated with the age at the start of treatment (r=−0.34, P=0.01) and the pretreatment IGF-1 level (r=−0.37, P=0.04).Conclusion GH therapy improved HtSDS even to exceed MPHSDS in children with FSS. Children with normal stature while far below MPHSDS had their HtSDS improved with GH therapy while did not reach their MPHSDS. The duration and age at the start of GH therapy are important parameters for the favorable outcome. MPHSDS is an important parameter in GH therapy decision.

Factors influencing growth in children with growth hormone deficiency - a case-control study.

To assess the response of South Indian children with growth hormone deficiency (GHD) to growth hormone therapy, optimal duration of therapy for good catch up, and factors determining the response of our children to growth hormone therapy. We conducted acase control study at apaediatric endocrine unit of atertiary paediatric hospital. Children diagnosed with growth hormone deficiency were initiated on GH (cases) or followed up without GH therapy (controls). Detailed clinical, biochemical, radiological, and treatment parameters were recorded at baseline and follow-up. Data were analysed using IBM SPSS version 21. We enrolled 23 subjects in group I (cases who received GH) and group II (controls with untreated children), and both the groups were comparable at baseline. Group I (-4.12 ±1.7 to -2.81 ±1.52) had significant height increase on follow-up after GH therapy compared to group II (-3.55 ±1.7 to -3.51 ±1.52) (p>0.05). Growth velocity in group I (13.25 ±5.6 cm/year, SD score 4.55 ±5.42) was significantly higher compared to group II (3.4 ±1.8 cm/year, SD score -1.62 ±2.38). Duration of growth hormone therapy, presence of ectopic posterior pituitary, and BA: CA ratio independently impacted the growth velocity SD scores. Kaplan Meier analysis curve showed 15 months of GH therapy was needed to attain aheight within ±2 SD of the target height. Early diagnosis, pre-pubertal status, delayed bone age, and presence of ectopic posterior pituitary on MRI are determinants of abetter response. Growth hormone must be administered for at least 15 months for catch up height SDs within target height SD range.

Vitamin D3 and Dental Caries in Children with Growth Hormone Deficiency.

Vitamin D deficiency is a common risk factor for multifactorial diseases, and it seems to be associated with growth hormone deficiency (GHD). Vitamin D could prevent dental caries. The goal of this study was to identify whether there is an association between hormonal therapy with growth hormone (GH), vitamin D3 supplementation, vitamin D3 levels, and the occurrence of caries among children affected by GHD. The study group consisted of patients from the Department of Endocrinology and Diabetology of the University Paediatric Hospital at the Medical University of Lublin treated with recombinant human GH for pituitary GHD. It was conducted between October 2014 and June 2015. The study group included 121 children and adolescents aged 6 to 18 years, with 56 children from rural areas and 65 from urban areas. The study group was stratified by the area of residence. We found the statistically significant impact of vitamin D3 concentration on the average value of the DMFT (decayed, missed, and filled teeth) index and its component—DT (decayed teeth), which was noted in subjects from rural areas. Among patients from urban areas, we found a statistically significant correlation between duration of therapy and the DMFT index. An increase in duration of GH therapy by 10 months leads to a mean increase in DMFT index by 0.70. Based on multiple regression analysis, we developed the following model: value of DT = 3.10 − 0.73∗category of vitamin D3 concentration − 0.07∗duration of supplementation (in months). In this model, variables with a significant impact on the value of DT in the group of patients from rural areas include time of vitamin D3 supplementation and category of vitamin D3 concentration. Greater emphasis should be placed on promoting vitamin D3 as a potentially effective agent reducing the number of dental caries, especially among patients with GHD.

Growth hormone therapy in patients with Noonan syndrome.

Noonan syndrome (NS) is an autosomal dominant disorder that involves multiple organ systems, with short stature as the most common presentation (>70%). Possible mechanisms of short stature in NS include growth hormone (GH) deficiency, neurosecretory dysfunction, and GH resistance. Accordingly, GH therapy has been carried out for NS patients over the last three decades, and multiple studies have reported acceleration of growth velocity (GV) and increase of height standard deviation score (SDS) in both prepubertal and pubertal NS patients upon GH therapy. One year of GH therapy resulted in almost doubling of GV compared with baseline; afterwards, the increase in GV gradually decreased in the following years, showing that the effect of GH therapy wanes over time. After four years of GH therapy, ~70% of NS patients reached normal height considering their age and sex. Early initiation, long duration of GH therapy, and higher height SDS at the onset of puberty were associated with improved final height, whereas gender, dosage of GH, and the clinical severity did not show significant association with final height. Studies have reported no significant adverse events of GH therapy regarding progression of hypertrophic cardiomyopathy, alteration of metabolism, and tumor development. Therefore, GH therapy is effective for improving height and GV of NS patients; nevertheless, concerns on possible malignancy remains, which necessitates continuous monitoring of NS patients receiving GH therapy.

Impact of Age and Duration of Growth Hormone Therapy in Children with Turner Syndrome

Background/Aims: To assess height standard deviation scores (HSDS) in patients with Turner syndrome (TS) by age at treatment initiation and varying durations of treatment with growth hormone (GH). Methods: GH treatment-naïve patients with TS from the American Norditropin Studies: Web-enabled Research (ANSWER) Program® Registry were analyzed at baseline, 4 months, and annually. Results: Three hundred and eighty-two patients with TS had a baseline mean (±SD) HSDS of –2.6 ± 0.9. Patients received short-term (1 year), long-term (<3 years), and extended GH treatment (≧3 years, mean = 4.54 years), resulting in 40.2% (n = 99/246), 60.5% (n = 69/114), and 62.3% (n = 86/138) of the patients achieving HSDS >–2. Patients starting GH at a younger age experienced better growth response, regardless of treatment duration. Change in HSDS from baseline (ΔHSDS) at 4 months correlated positively with ΔHSDS at 1 and 3 years, and ΔHSDS at 1 year with ΔHSDS at 3 years (p values from 0.0017 to<0.0001). Conclusions: Height gains in patients with TS during short-term treatment were found to be highly predictive of longer-term results. Continuation of GH treatment (≧3 years) resulted in 62.3% of the patients achieving an HSDS within the normal population range, indicating the clinical importance of early initiation and continuation of GH treatment in patients with TS.

Effect of Growth Hormone Therapy on Adult Height of Children with Turner Syndrome

Short stature is a common manifestation of Turner syndrome. The purpose of this study was to evaluate the effect of growth hormone (GH) therapy alone on the adult height of children with Turner syndrome. From 1987 to 2006, 21 Turner syndrome patients who had been treated with GH for >2 years and had reached adult height were enrolled in the study. The dosage of GH was 0.33 mg/kg/week. Estrogen replacement therapy was prescribed at the age of 15.6+/-0.9 years, if indicated. The patients had been followed-up until they reached their adult height. During the same period, 28 Turner syndrome patients who were not treated with growth-promoting agents were enrolled for comparison. Mann-Whitney U test and Wilcoxon signed rank test were used for comparison. Twenty-one patients in the study group started GH therapy at the age of 11.5+/-1.8 years. The duration of GH therapy was 4.0+/-1.5 years. The growth rate before treatment was 3.8+/-0.7 cm/year, which increased to 7.1+/-1.4, 5.4+/-1.4 and 4.7+/-0.9 cm/year during the first 3 years of GH therapy, respectively. Patients who received GH reached an adult height of 150.0+/-5.1 cm, which was significantly higher than the 144.7+/-5.9 cm of the control group (p<0.05). The adult height of the study group was 6.3+/-3.3 cm taller than their projected adult height upon enrolment. No major adverse events were detected during GH therapy. GH alone is safe and effective for the promotion of growth in children with Turner syndrome in Taiwan.

Acute Hyperglycaemia Impairs Cognitive Function in Children with IDDM

The role of growth hormone (GH) in obesity is controversial. Childhood obesity is characterized by reduced GH secretion. Low, high and normal serum insulin-like growth factor-I (IGF-I) levels have been described in obese children in the face of low GH secretion. There is conflicting information on the interaction of GH and obesity upon components of the GH-IGF-I-insulin-like growth factor binding proteins (IGFBPs) system and its relationship to cardiovascular risk factors. This review highlights the role of GH modulating cardiovascular risk factors, including lipid levels, inflammatory markers, cardiac and endothelial function in children and adolescents with obesity and insulin resistance. The interplay between GH secretion, NO production, IGF-I, IGFBP-1, and IGFBP-3 levels, lipid profile, insulin sensitivity and the degree of visceral obesity necessitates further study. These metabolic parameters may be useful markers of premature atherosclerosis in children with obesity. Further studies should address the question of optimal dose and duration of GH therapy in non-GH deficient obese patients with metabolic disturbances at risk for premature atherosclerosis.

Pubertal Height Gain in Ullrich-Turner Syndrome

Short stature and ovarian failure are the main features in Ullrich-Turner syndrome (UTS). The aim of this retrospective analysis was to evaluate the influence of age at initiation of puberty on final height. Sixty-five girls were treated with growth hormone (GH) and had a final height of 150.6 +/- 5.7 cm; 12/65 entered puberty spontaneously. A non-GH treated group of 12 girls with UTS reached a final height of 147.3 +/- 6.6 cm. Subdividing the GH treated group (n = 53) based on the age at induction of puberty, before or after 13 years, there was no significant difference in final height. Final height was affected by the age at which GH treatment was initiated, height SDS at the beginning of puberty, and by the duration of GH therapy. Therefore, early treatment with GH for short stature in UTS should be attempted so that an age adequate initiation of puberty will be feasible.

Long-term results of growth hormone therapy in Turner syndrome.

Short stature is one of the main features of Turner syndrome. Today, most patients are treated with growth hormone (GH) to improve adult height. We have reviewed the literature reporting adult height in patients with Turner syndrome treated with GH alone or in combination with oxandrolone. The reported adult heights as well as the height gain over projected or predicted height are still preliminary and vary considerably among studies. There is some evidence that the age of onset of therapy, dose of GH, duration of GH therapy, target height, time of estrogen substitution, or concurrent treatment with oxandrolone affect adult height. The reported height gains over projected height range from -0.20 to +16.0 cm (median: 5.1 cm) in patients treated with GH and from +0.68 cm to +10.3 (median: 6.40 cm) in patients treated with GH and oxandrolone. Thus, the presently available data are extremely varied and need further detailed analysis after all ongoing clinical trials have published the final results of all patients included in the study.

Academic Outcomes Among Children and Adolescents Receiving Growth Hormone Therapy

In this study we assessed the prevalence of academic difficulties among children and adolescents (103 boys and 47 girls ages 6-18 years) presently receiving growth hormone (GH) therapy in a cross-sectional study. Psychoeducational functioning was assessed by parent report. Between 18% and 29% of the youths were performing poorly in at least one of four key academic subjects, and 26% had been classified as educationally "handicapped." Those with growth failure attributable to more medically involved conditions exhibited greater academic difficulty. Severity of short stature, duration of GH therapy, and growth-responsiveness to treatment were not significantly related to academic problems. The finding that academic difficulties are commonly observed among youths receiving GH therapy underscores the importance of developing a remediation plan as early as possible. Our study does not support the proposition that GH-mediated improvements in growth normalize academic achievement.

Predictors of Adult Height in Girls with Turner Syndrome Treated with Growth Hormone † 408

It is generally recognized that growth hormone (GH) therapy can improve the adult height of girls with Turner syndrome (TS). It has been difficult to quantify the ultimate effect of GH therapy on adult height and to examine the factors that might affect efficacy. Potential predictors of adult height include: age of initiation of GH therapy, frequency of GH injections, GH dose, age of initiation of estrogen therapy, height relative to age at initiation of GH therapy, bone age at initiation of GH therapy, parent heights, duration of GH therapy, and karyotype. In a clinical study in which 60 of 117 girls with TS began GH therapy before age 11 yrs, 30 of these girls were randomized to receive estrogen at age 12 and 30 at age 15. A comparison of treated girls with last measured height after age 13.5 yrs with untreated historical controls with heights obtained after 18 yrs showed a gain of 5.9 cm in the early estrogen group (n=26) and 8.3 cm in the late estrogen group (n=29)(ANCOVA p < 0.01 between groups). In a multiple regression analysis of adult height for girls with last height measured after age 16 yrs, the only significant predictor of adult height gain over expected adult height (based on the projection of childhood Turner-standardized height) was the number of years of GH therapy before initiation of estrogen therapy (n=29, p < 0.0001). The mean increase in adult height over expected was 2.1 cm for each year of GH therapy prior to estrogen therapy.

Lack of effect of growth hormone therapy on the count and density of melanocytic naevi in children.

An observation of accelerated growth of acquired melanocytic naevi (AMN) during treatment with human growth hormone (GH) raised concerns about the potential risk of melanoma in treated patients. An increased number of AMN, rather than growth rate, is associated with a higher risk for melanoma. It is unknown whether treatment with GH causes an increase in numbers of AMN. We evaluated the effect of GH treatment on the number of AMN in a cross-sectional study of 90 children with GH deficiency. AMN counts and densities in these children were compared with those found in a control group of 100 children. Factors potentially related to increased numbers of AMN, such as age, sex, skin colour, number of episodes of sunburn and duration of GH therapy were determined. Among the various factors, only the age and colour of unexposed skin area were predictive for the total number and density of AMN. No correlation was found between the AMN counts or density and the duration of GH therapy. There was no difference in AMN counts or density between the GH-deficient patient group and the control groups. We conclude that GH therapy in children is not associated with increased AMN count and density and is unlikely to potentiate the risk for melanoma in these children.

Skeletal dysplasias: response to growth hormone therapy.

This study was conducted to determine the response of children with skeletal dysplasia and short stature to growth hormone therapy and whether such therapy is appropriate in skeletal dysplasia. A retrospective analysis of the Australia-wide group of children with skeletal dysplasia registered on the Ozgrow database, using growth data at commencement and at 12 monthly intervals. Eighteen females and 35 males received growth hormone (GH) therapy for at least 12 months. Patients were aged 10.3 +/- 3.3 (mean +/- s.d.) years and had severe short stature with height standard deviation score (SDS) of -3.5 +/- 1.0 (mean +/- s.d.). Hypochondroplasia (N = 7), metaphyseal dysplasia (N = 5) and dyschondrosteosis (N = 5) were the most frequently represented specific skeletal dysplasia subgroups. These groups and the remaining heterogeneous group did not differ significantly at baseline or subsequent growth response. Duration of GH therapy was mean (range) 36 mo (12-60 mo). Sex, age or degree of short stature did not correlate with response to GH therapy. delta height SDS was 0.3 (mean) after 12 months of GH therapy, which corresponded to an increase in mean growth velocity from 4.3 cm/yr to 6.9 cm/yr. Mean GV declined after the first year, and by 36 months was only 1.1 cm/year above baseline, while delta height SDS was 0.8 The results suggest that growth hormone therapy is not generally effective for treatment of short stature in skeletal dysplasia.