Increase In Height Standard Deviation Score Research Articles

Growth Hormone Therapy: Comparison of Short- and Long-Term Outcomes between Children with Growth Hormone Deficiency and Small for Gestational Age

Introduction: Direct comparisons of both short-term and long-term auxological outcomes of growth hormone therapy (GHT) between growth hormone deficiency (GHD) and small for gestational age (SGA) are scarce. Methods: One hundred three patients with GHD and 53 patients with SGA treated at our tertiary center were investigated. Short-term and long-term outcomes were compared between these groups using multivariable linear regression models with adjustment for age, sex, and height at therapy start, also allowing for sex-specific group comparisons. Results: Mean delta height standard deviation scores (SDS) after 1 year of treatment were significantly higher in GHD (0.90, CI: 0.82–0.99) compared to SGA (0.67, CI: 0.54–0.79) (p = 0.003) with no sex difference. As expected, the mean increase in height SDS at final height (FH) was significantly higher in GHD (2.21, CI: 2.00–2.42) compared to SGA (1.05, CI: 0.75–1.35) (p < 0.001), leading to a target height corrected FH of −0.39 SDS (CI: −0.62 to −0.15) in GHD and −1.22 SDS (CI: −1.57 to −0.87) in SGA (p < 0.001). Girls with GHD had a better long-term outcome, as did boys with SGA when compared to the respective opposite sex. The cut-off of delta height of 0.5 SDS during the first year had a low sensitivity to detect long-term non-responders. We found a relation between short-term and long-term outcomes in GHD but not in SGA (adjusted R2 = 0.66 vs. 0.01). Conclusion: In contrast to GHD, we observed practically no relationship between 1st-year and long-term outcomes in SGA patients treated with GH.

FRI454 The Effect Of Growth Hormone Treatment According To Karyotype Classification In Turner Syndrome Patients

Abstract Disclosure: J. Choi: None. J. Yu: None. H. Kim: None. OBJECTIVES Short stature is the main characteristics for Turner syndrome (TS) patients, and growth hormone (GH) therapy has been used as an essential treatment for developing final adult height. However, there are only a few studies on the difference responsiveness to GH therapy according to the karyotype of Turner syndrome in Korea. The aim of this study was to analyze the effect of different types of TS karyotype abnormality on the response of GH therapy. METHODS The clinical parameters of 194 TS patients registered in the LG Growth Study, who received rhGH therapy (Eutropin inj.,LG Chem Ltd.,Korea) between February 2001 and October 2021, were retrospectively reviewed. Data for four group of subjects were obtained as follow: Monosomy X (n=56); Mosaicism without X structural abnormality (n=41); Mosaicism with X structural abnormality (n=71); X Structural abnormality (n=26). Parameters of biochemical characteristics and growth responses were compared during 3-year GH treatment. RESULTS The baseline height standard deviation score (SDS) was -2.85±0.86 in total TS patients. The growth velocity (cm/year) in the second year was higher in the Mosaicism without X structural abnormality compared to the monosomy X patients. However, the change of Hight SDS over three years was not statistically different between karyotypes. The growth rate was the highest in the first year, and it showed a decreasing trend over time. There was an increase in Height SDS due to growth hormone treatment for three years. The variables affecting the 0-3rd Δ height SDS were not found in the regression analysis CONCLUSIONS Our results indicate that there are no difference in response to three years of growth hormone therapy according to karyotype of TS. It was found that the initial height SDS was the lowest in monosomy compared to the others group. Further studies should be performed on other factors influencing the efficacy of the therapy. Presentation Date: Friday, June 16, 2023

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.

Pubertal Timing and Growth Dynamics in Children With Severe Primary IGF-1 Deficiency: Results From the European Increlex® Growth Forum Database Registry.

BackgroundPuberty is delayed in untreated children and adolescents with severe primary IGF-1 deficiency (SPIGFD); to date, it has not been reported whether recombinant human insulin-like growth factor-1 mecasermin (rhIGF-1) treatment affects this. Pubertal growth outcomes were extracted from the European Increlex® Growth Forum Database (Eu-IGFD) Registry (NCT00903110).MethodsThe Eu-IGFD Registry includes children and adolescents aged 2 to 18 years with growth failure associated with SPIGFD who are treated with rhIGF-1. Reported outcomes include: age at last registration of Tanner stage 1 and first registration of Tanner stage 2-5 (T2-T5; based on breast development for girls and genital development for boys, respectively); maximum height velocity during each Tanner stage; and pubertal peak height velocity (PPHV). Data cut-off was 13 May 2019.ResultsThis analysis included 213 patients (132 boys and 81 girls). Mean (SD) age at last registration of T1 and first registration of T5 was 13.0 (2.0) and 16.3 (1.6) years, respectively, in boys and 11.6 (1.8) and 14.7 (1.5) years, respectively, in girls. Among patients reaching the end of puberty (25 boys and 11 girls), mean (SD) height SDS increased from -3.7 (1.4) at baseline in the Eu-IGFD Registry to -2.6 (1.4) at T5 in boys and from -3.1 (1.1) to -2.3 (1.5) in girls. Maximum height velocity was observed during T2 in girls and T3 in boys. Median (range) PPHV was 8.0 (0.3–13.0) cm/year in boys and 6.8 (1.3–9.6) cm/year in girls and occurred most frequently during T2. Overall, the adverse events seen in this analysis were in line with the known safety profile of rhIGF-1.ConclusionChildren and adolescents treated with rhIGF-1 for SPIGFD with growth failure experienced an increase in height SDS in prepubertal years compared with baseline. Despite 1.5 years delay in pubertal start and a delayed and slightly lower PPHV, height SDS gain during puberty was maintained.

Acceleration in BMI gain following COVID-19 restrictions. A longitudinal study with 7- to 10-year-old primary school children.

SummaryBackgroundThe ramifications of COVID‐19 restrictions might accelerate the already rising proportion of children with overweight or obesity.ObjectivesTo assess the association between COVID‐19 restrictions and changes in body mass index (BMI) and the proportion of children with overweight or obesity.MethodsCohort study with baseline measurements in September 2019 (prior to COVID‐19 restrictions) and follow‐up in June 2020, September 2020, and March 2021 at 12 primary schools in Austria. The height and weight of 738 children aged 7 to 10 years were measured and age‐ and sex‐specific national and international standardized values were calculated. Changes over time were analysed by analysis of variance.ResultsMean BMIIOTF standard deviation scores (SDS) increased by 0.24 (95% CI, 0.21–0.28) between September 2019 and March 2021. The proportion of children with overweight or obesity increased from 20.7% to 26.2% during this period (p < 0.001) using national reference values—EQUI BMIAUT—comparable results were observed. Simultaneously, the heightAUT SDS increased by 0.06 (95% CI, 0.05–0.08) with a larger increase in girls (+0.11; p < 0.001) than in boys (+0.03; p = 0.19).ConclusionsCOVID‐19 restrictions were associated with accelerated increases in mean BMI and the proportion of children with overweight or obesity. The increase in height SDS in girls calls for further investigations.

Changes, limitations, and prospects of adult height in GH treatment for Japanese GHD patients.

For the treatment of pituitary dwarfism (called pituitary short stature in 1987 and renamed as growth hormone deficiency [GHD] in 1993), pituitary-derived human growth hormone (phGH) was approved in 1975, and recombinant hGH (rhGH) was approved in 1988. Adult height in patients with isolated GH deficiency (IGHD) improved by 2000. However, this improvement was mainly due to the increase in height SDS at treatment initiation. Although the mean adult height in patients with idiopathic GHD has been reported to be approximately -1.0 SD or higher in Europe and the United States, the mean adult height of patients with idiopathic GHD in Japan has not improved as much as that in Europe and the United States after 2000. The possible reasons were: low therapeutic doses than those in Europe and the United States; changes in background factors, such as reduction in severe GHD; differences in response to GH between Caucasians and Japanese; and, no increase in height at puberty onset because delayed puberty was normalized by GH treatment. In the future, long-acting GH is expected to improve adult height in GHD patients in Japan.

Floating-Harbor Syndrome Treated With Recombinant Human Growth Hormone: A Case Report and Literature Review.

Introduction: We aimed to summarize the clinical characteristics of Floating-Harbor syndrome (FHS) and the effect of recombinant human growth hormone (rhGH) to increase height.Methods: The clinical manifestations, gene sequencing results, treatment, and regression of one child with FHS were reported at the Department of Pediatrics, General Hospital of Tianjin Medical University, in July 2020. PubMed was searched using the keyword “Floating-Harbor Syndrome” up to March 2021 to obtain clinical information on children with FHS for review.Results: The child, who was a male aged 6 years and 9 months, presented to the clinic with main complaints of delayed language development since childhood and a short stature for 4 years. The child's short stature, peculiar facial features, delayed language development, and delayed bone development were considered alongside genetic testing and Sanger sequencing to verify the results. A heterozygous mutation (c.7401delC; p.Ile2468Phefs*7) was identified in exon 34 of the SRCAP gene, which was a frameshift mutation, and Sanger verification showed that neither parent had this mutation. The child was administered subcutaneous injection of rhGH (0.13 U/kg/day) and was followed up regularly. At the time of writing, the child had been treated for 6 months and was 7 years and 3 months old with a height of 106.3 cm (−3.69 SDS), which was a height increase of 6.3 cm. The patient did not complain of discomfort during treatment and presented normal laboratory tests results. Twenty-two children with FHS treated with rhGH were included in the literature review, and most of these patients demonstrated an increase in height SDS without adverse effects.Conclusion: Short stature, delayed skeletal maturation, impaired language expression, intellectual deficits, and peculiar facial features are the main clinical features of FHS. rhGH can be used as a treatment to increase height in patients with FHS, but its effectiveness and safety still need to be monitored in larger sample sizes over longer periods of time.

Natural history of facial and skeletal features from neonatal period to adulthood in a 3M syndrome cohort with biallelic CUL7 or OBSL1 variants

3M syndrome is characterized by severe pre- and post-natal growth restriction, typical face, slender tubular bones, tall vertebral bodies, prominent heels and normal intelligence. It is caused by biallelic variants of CUL7, OBSL1 and, more rarely, CCDC8. The aim of this study is to evaluate facial and skeletal findings in 3M patients from neonatal period to adulthood. A total of 19 patients with a median age of diagnosis of 9.2 months were included in this study and were followed for two to 20 years. CUL7 and OBSL1 variants were found in 57.9% and 42.1% of patients, respectively, five of which are novel. Most of patients had triangular face, frontal bossing, short fleshy nose, full fleshy lower lip, transverse groove of rib cage, hyperlordosis and prominent heels. Three new early-diagnostic signs were observed in infants; two were infraorbital swelling of the lower lid and facial infantile hemangioma, both of which became less pronounced with aging. The third was the central tubercle of the upper lip that became more prominent with in time. While slender long bones did not change with aging, the tall vertebral bodies became more prominent radiologically. The mean birth length in patients was −4.3 SDS. Eight patients reached a mean final height of −4.9 SDS. Despite described growth hormone (GH) insensitivity in 3M syndrome, 12 patients either with GH deficiency or with normal GH levels were treated with GH; seven patients responded with an increase in height SDS. This study not only provided early diagnostic signs of the syndrome, but also presented important follow-up findings.

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome

Objective:To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey.Methods:The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated.Results:The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged.Conclusion:The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.

Impact of Growth Hormone Therapy on Adult Height in Patients with PTPN11 Mutations Related to Noonan Syndrome

Objectives: The aim of this study was to evaluate the response to recombinant human growth hormone (rhGH) treatment in patients with Noonan syndrome (NS). Materials and Methods: Forty-two patients (35 PTPN11+) were treated with rhGH, and 17 were followed-up until adult height. The outcomes were changes in growth velocity (GV) and height standard deviation scores (SDS) for normal (height-CDC SDS) and Noonan standards (height-NS SDS). Results: The pretreatment chronological age was 10.3 ± 3.5 years. Height-CDC SDS and height-NS SDS were –3.1 ± 0.7 and –0.5 ± 0.6, respectively. PTPN11+ patients had a better growth response than PTPN11– patients. GV SDS increased from –1.2 ± 1.8 to 3.1 ± 2.8 after the first year of therapy in PTPN11+ patients, and from –1.9 ± 2.6 to –0.1 ± 2.6 in PTPN11– patients. The gain in height-CDC SDS during the first year was higher in PTPN11+ than PTPN11– (0.6 ± 0.4 vs. 0.1 ± 0.2, p = 0.008). Similarly, the gain was observed in height-NS SDS (0.6 ± 0.3 vs. 0.2 ± 0.2, respectively, p < 0.001). Among the patients that reached adult height (n = 17), AH-CDC SDS and AH-NS SDS were –2.1 ± 0.7 and 0.7 ± 0.8, respectively. The total increase in height SDS was 1.3 ± 0.7 and 1.5 ± 0.6 for normal and NS standards, respectively. Conclusions: This study supports the advantage of rhGH therapy on adult height in PTPN11+ patients. In comparison, PTPN11– patients showed a poor response to rhGH. However, this PTPN11– group was small, preventing an adequate comparison among different genotypes and no guarantee of response to therapy in genes besides PTPN11.

Efficacy and safety of recombinant human growth hormone in treating Chinese children with idiopathic short stature

ObjectiveThis study aims to investigate the efficacy and safety of recombinant human growth hormone (rhGH) in the treatment of idiopathic short stature (ISS). MethodsThe data of 200 ISS children, who were treated with rhGH from January 2008 to December 2016, were collected and retrospectively analyzed. The data of height, bone age(BA), chronological age(CA), fasting blood glucose, fasting insulin, thyroid function and IGF-1 were collected, and annual growth velocity (GV), height standard deviation score (HtSDS) and related factors that affect GV were statistically analyzed. Results(1) GV and HtSDS changes: As the time of treatment increased, the GV decreased year by year. The GV in the second year was significantly lower than that in the first year (P < .0001), and the GV in the fourth year was significantly lower than that in the third year (P < .05). HtSDS gradually increased from the first year to the third year, and became significantly higher than that in the year before the treatment (P < .01). The difference in the increase in HtSDS between the fourth year and third year was not statistically significant (P > .05). (2) The influence factors of GV included age at initial treatment, IGF-1SDS during treatment and GV in the year before treatment. (3) The most common side effects during treatment included transient hyperglycemia and temporary hyperinsulinemia, and these returned to normal after the treatment was stopped. Some patients presented with accelerated bone age growth after two years of treatment (annual growth of bone age △BA was >2 years), compared with children without accelerated bone age growth, and the difference between BA and CA (BA-CA) was significantly reduced at the beginning of the treatment (P < .01). ConclusionrhGH has a good growth promoting effect on ISS children. A variety of factors may affect the GV, and related adverse reactions should be monitored during the treatment.

Phenotypic spectrum and responses to recombinant human IGF1 (rhIGF1) therapy in patients with homozygous intronic pseudoexon growth hormone receptor mutation.

Patients with homozygous intronic pseudoexon GH receptor (GHR) mutations (6Ψ) have growth hormone insensitivity (GHI) (growth failure, IGF1 deficiency and normal/elevated serum GH). We report 9 patients in addition to previously described 11 GHR 6Ψ patients and their responses to rhIGF1 therapy. 20 patients (12 males, 11 families, mean age 4.0 ± 2.2 years) were diagnosed genetically in our centre. Phenotypic data and responses to rhIGF1 treatment were provided by referring clinicians. Continuous parametric variables were compared using Student t-test or ANOVA. 10/20 (50%) had typical facial features of GHI, 19/20 (95%) from consanguineous families and 18/20 (90%) of Pakistani origin. At diagnosis, mean height SDS: -4.1 ± 0.95, IGF1 SDS: -2.8 ± 1.4; IGFBP3 SDS: -3.0 ± 2.1 and mean basal and peak GH levels: 11.9 µg/L and 32.9 µg/L, respectively. 1/12 who had IGF1 generation test, responded (IGF1: 132-255 ng/mL). 15/20 (75%; 11M) received rhIGF1 (mean dose: 114 µg/kg twice daily, mean duration: 5.3 ± 2.5 years). Mean baseline height velocity of 4.7 ± 1.1 cm/year increased to 7.4 ± 1.8 cm/year (P = 0.001) during year 1 of therapy. Year 3 mean height SDS (-3.2 ± 1.0) was higher than pre-treatment height SDS (-4.3 ± 0.8) (P = 0.03). Mean cumulative increase in height SDS after year 5 was 1.4 ± 0.9. Difference between target height (TH) SDS and adult or latest height SDS was less than that of TH SDS and pre-treatment height SDS (2.1 ± 1.2 vs 3.0 ± 0.8; P = 0.02). In addition to phenotypic heterogeneity in the cohort, there was mismatch between clinical and biochemical features in individual patients with 6Ψ GHR mutations. rhIGF1 treatment improved height outcomes.

The Effect of Clonidine Therapy on Height and Growth Velocity in Constitutional Growth and Puberty Delay

Background: Constitutional delay of growth and puberty (CDGP) is the most common cause of short stature. This variant of normal growth can be associated with psychological stress in some affected individuals. Objectives: We aimed to assess the effects of clonidine on short-term growth rate in children and adolescents with constitutional growth delay. Patients and Methods: In this prospective, randomized clinical trial study, 48 prepubertal constitutionally short boys (6 -12 years old) with height standard deviation scores (HSDS) less than -2, bone age delay 2.1 ± 0.2 years, GH concentration > 10 μg/L after provocation and growth rates < 5 cm/year were included. Subjects were randomly assigned to group A (n = 24) who received clonidine 0.1 mg/m2 or group B (n = 24) who received placebo before sleep for 6 months. Height, weight and growth velocity were measured in 6th and 12th months. Results: Mean age and height in two groups were similar at baseline. Mean growth velocity in group A was 2.9 ± 0.91 and 3.1 ± 0.98 cm/6 month at baseline and 6th months, respectively and in group B was 2.9 ± 0.94 and 2.4 ± 0.47 cm/6 month at baseline and 6th months, respectively (P = 0.01). Mean HSDS in group A was -2.79 ± 0.65 and 2.39 ± 0.39 at baseline and 6th months, respectively and in group B was 2.69±0.73 and 2.39 ± 0.48 at baseline and 6th months, respectively. Conclusions: Although a slightly increase in HSDS was observed in treated group, but difference was not significant compared with control subjects. So, clonidine therapy could not improve height standard deviation score and growth velocity of children and adolescents with CDGP.

A 2-year multicentre, open-label, randomized, controlled study of growth hormone (Genotropin®) treatment in very young children born small for gestational age: Early Growth and Neurodevelopment (EGN) Study.

In Europe, growth hormone (GH) treatment for children born small for gestational age (SGA) can only be initiated after 4 years of age. However, younger age at treatment initiation is a predictor of favourable response. To assess the effect of GH treatment on early growth and cognitive functioning in very young (<30 months), short-stature children born SGA. A 2-year, randomized controlled, multicentre study (NCT00627523; EGN study), in which patients received either GH treatment or no treatment for 24 months. Children aged 19-29 months diagnosed as SGA at birth, and for whom sufficient early growth data were available, were eligible. Patients were randomized (1:1) to GH treatment (Genotropin®, Pfizer Inc.) at a dose of 0·035 mg/kg/day by subcutaneous injection, or no treatment. The primary objective was to assess the change from baseline in height standard deviation score (SDS) after 24 months of GH treatment. Change from baseline in height SDS was significantly greater in the GH treatment vs control group at both month 12 (1·03 vs 0·14) and month 24 (1·63 vs 0·43; both P < 0·001). Growth velocity SDS was significantly higher in the GH treatment vs control group at 12 months (P < 0·001), but not at 24 months. There was no significant difference in mental or psychomotor development indices between the two groups. GH treatment for 24 months in very young short-stature children born SGA resulted in a significant increase in height SDS compared with no treatment.

Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy: longitudinal analysis of growth-hormone-naïve patients enrolled in the NordiNet® International Outcome Study and the ANSWER Program.

BackgroundTurner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS) or the American Norditropin Studies: Web-Enabled Research (ANSWER) Program, which collect information on GH therapy in clinical practice.MethodsRepeated-measures regression analysis was performed on change in height standard deviation score (HSDS) and target-height-corrected HSDS, based on national normal references and treatment-naïve disease-specific references. Models were adjusted for baseline age and HSDS, and average GH dose. The study population was paediatric patients with TS and NS in the NordiNet® IOS and ANSWER Program. Longitudinal growth responses over 4 years were evaluated.ResultsIn 30 NS patients (24 males; baseline age 8.39 ± 3.45 years) and 294 TS patients (7.81 ± 3.22 years), 4-year adjusted ΔHSDS were +1.14 ± 0.13 and +1.03 ± 0.04, respectively (national references). Based on untreated, disease-specific references, 4-year adjusted ΔHSDS for NS and TS were +1.48 ± 0.10 and +1.79 ± 0.04. The analyses showed a significant increase in HSDS over time for both NS and TS (P < 0.0001). ΔHSDS in NS was higher with younger baseline age; ΔHSDS in TS was higher for patients with younger baseline age and higher GH dose.ConclusionsNS and TS patients responded well and similarly over 4 years of GH treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13633-015-0015-1) contains supplementary material, which is available to authorized users.

Quality of life of young adults after a growth hormone therapy with childhood onset

Little is known about the health-related quality of life of young adults with childhood onset idiopathic growth hormone deficiency or neurosecretory dysfunction of growth hormone secretion, who have been treated with recombinant human growth hormone (GH). Patients were diagnosed and treated with human growth hormone at the University Children´s Hospital in Erlangen (n=85). The data of both groups were merged for analysis, because no difference between idiopathic growth hormone deficiency and neurosecretory dysfunction of growth hormone secretion in auxological. Data were found. Health-related quality of life was cross- sectionally assessed after the end of growth hormone therapy with the Short Form-36 Health Survey and the Nottingham Health Profiles for which population based norm data are available. At the time of the survey, the patients (53 m, 32 f) were 23.5 ± 4.6 years old. At start of GH therapy, age was 10.5 ± 2.8 and at the end 16.3 ± 1,4 years. At start, height SDS was -3.20 ± 1.06. GH dose was 0,026 ± 0,012 mg/kg/d (daily s. c.-injections). The increase in height SDS after the end of GH therapy was 1.69 ± 1.22. Compared to the reference population, patients reported significantly lower scores on the scales energy level, vitality, social functioning, indicating a greater social isolation, a stronger emotional reaction, an increased loss of mobility and a worse psychological state. Young adults report specific impairments after completion of GH therapy.

Longitudinal growth on an everolimus- versus an MMF-based steroid-free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case-control study on longitudinal growth over 2 years in steroid-free pediatric renal transplant recipients. Fourteen patients on a steroid-free maintenance immunosuppressive regimen consisting of low-dose everolimus (EVR) in conjunction with low-dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid-free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch-up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid-free pediatric patients on low-dose EVR and CsA is not different to that of a matched steroid-free control group on an immunosuppressive regimen with standard-dose CNI and MMF. Hence, low-dose EVR does not appear to negatively impact short-term growth in pediatric renal transplant recipients.

Long-Term Growth Hormone Therapy is Associated With a Dose-Dependent Increase in Height SDS and Insulin-Like Growth Factor-I SDS in Short Japanese Children Born Small for Gestational Age

In children with short stature born small for gestational age (SGA), growth hormone (GH) treatment is associated with an acceleration of growth allowing most to achieve an adult height adequate for their target height. The pathophysiology of growth failure may arise from anomalies in the GH–IGF axis, including deficits in GH/IGF-I concentrations and/or GH/IGF-I sensitivity.

Efficacy of IGF‐based growth hormone (GH) dosing in nonGH‐deficient (nonGHD) short stature children with low IGF‐I is not related to basal IGF‐I levels

Weight-based GH dosing is the standard for treating children with short stature. The current study validates the usefulness of IGF-based GH dosing for GH therapy in nonGH-deficient (nonGHD) children and its relationship with pretreatment serum IGF-I concentration. In this twelve-month, open-label, randomized controlled study, 151 nonGHD (based on GH-stimulation tests), prepubertal children with short stature and IGF-I levels ≤ 33rd percentile [-0.44 standard deviation score (SDS)] were randomly assigned to receive GH (dose based on IGF-I titration algorithm; n = 114) or to observation (n = 37). GH dose (initially 40 μg/kg/d) was adjusted every 3 months to achieve an IGF-I SDS in the upper normal range (66-99 th percentile). In treated children, mean height SDS (HSDS) increased from -2.5 at baseline to -1.7 at 12 months and mean IGF-I SDS increased from -1.7 to 0.1. These parameters remained unchanged in untreated children. There was no relationship between change in HSDS (ΔHSDS) and degree of IGF-I deficiency at baseline. No safety problems were observed. Both groups had a similar advance in bone age. At the end of study, ΔHSDS in treated children showed a positive correlation with IGF-I SDS, but not with GH dose [mean 59 μg/kg/d (range 29-92)], basal IGF-I SDS or 1-month IGF parameters. In nonGHD subjects with short stature and serum IGF-I concentrations within and below the lower third of normal, adjusting GH dose to achieve an IGF-I level in the upper normal range resulted in a significant increase in HSDS, regardless of basal IGF-I levels.

Effect of 4 years of growth hormone therapy in children with Noonan syndrome in the American Norditropin Studies: Web-Enabled Research (ANSWER) Program® registry

BackgroundNoonan syndrome (NS) is a genetic disorder characterized by phenotypic features, including facial dysmorphology, cardiovascular anomalies, and short stature. Growth hormone (GH) has been approved by the United States Food and Drug Administration for short stature in children with NS. The objective of this analysis was to assess the height standard deviation score (HSDS) and change in HSDS (ΔHSDS) for up to 4 years (Y4) of GH therapy in children with NS.MethodsThe American Norditropin Studies: Web-Enabled Research (ANSWER) Program®, a US-based registry, collects long-term efficacy and safety information on patients treated with Norditropin® (somatropin rDNA origin, Novo Nordisk A/S) at the discretion of participating physicians. A total of 120 children (90 boys, 30 girls) with NS, naïve to previous GH treatment, were included in this analysis.ResultsThe mean (SD) baseline age of subjects (n = 120) was 9.2 (3.8) years. Mean (SD) HSDS increased from –2.65 (0.73) at baseline to –1.32 (1.11) at Y4 (n = 17). Subjects showed continued increase in HSDS from baseline to Y4 without significant differences between genders at Y1 or Y2. The mean (SD) GH dose was 47 (11) mcg/kg/day at baseline and 59 (16) mcg/kg/day at Y4. There was a negative correlation between baseline age and ΔHSDS at Y1 (R = –0.3156; P = 0.0055) and Y2 (R = –0.3394; P = 0.017). ΔHSDS at Y1 was significantly correlated with ΔHSDS at Y2 (n = 37; R = 0.8527, P < 0.0001) and Y3 (n = 20; R = 0.5145; P = 0.0203), but not Y4 (n = 12; R = 0.4066, P = 0.1896).ConclusionsGH treatment-naïve patients with NS showed continued increases in HSDS during 4 years of treatment with GH with no significant differences between genders up to 2 years. Baseline age was negatively correlated with ΔHSDS at Y1 and Y2. Whether long-term therapy in NS results in continued increase in HSDS to adult height remains to be investigated.Trial registrationClinicalTrials.gov NCT01009905