Final Height Standard Deviation Score Research Articles

The Manifestations and Complications of X-linked Hypophosphatemia in Saudi Arabia: A Retrospective Study

Background: X-linked hypophosphatemia (XLH) is a genetic disease of phosphate metabolism in which inactivating mutations of the phosphate regulating endopeptidase homolog, X-linked (PHEX) gene lead to local and systemic effects. In our pediatric clinics, XLH was observed to be associated with multiple complications despite conventional treatment. There is a need for novel treatment modalities to prevent disease progression and aid in the resolution of symptoms. Methods: This retrospective cross-sectional study aimed to understand the manifestations and complications of XLH in patients followed up at the endocrinology clinics in King Faisal Specialist Hospital and Research Center in Saudi Arabia. The study was conducted by reviewing the medical files of all XLH patients at the King Faisal Specialist Hospital and Research Center. Results: All the patients (N=24) who were included in this study had PHEX gene mutations. The mean age was 18.7 13.6 years and 68% were females. The mean height standard deviation score (HSDS) was ‑2.96 (-5.25 to -0.97) and 12 patients reached their final height (mean final HSDS, -3.28 [-1.39 to ‑5.39]). Skeletal deformities (mainly genu varum) were observed in 68% of the patients and 29% had craniosynostosis; 54% had undergone corrective osteotomy. Hyperparathyroidism was observed in 54% of the patients and 45% of the patients had nephrocalcinosis (grades 2/3). Conclusions: In our study, a majority of the XLH patients suffered from complications arising from the use of conventional therapy, thus indicating the need for novel treatment modalities for these patients. Additionally, no correlation between genotype and phenotype was found.

7548 Final adult height in children with idiopathic growth hormone deficiency after growth hormone treatment

Abstract Disclosure: H. Lee: None. S. An: None. M. Cho: None. H. Nam: None. Objective: The aim of this study was to assess the final adult height (FAH) achieved through recombinant human growth hormone (GH) treatment and the factors influencing FAH. Methods: We retrospectively reviewed the charts of all patients diagnosed with IGHD who were prepubertal when they began GH treatment since August 2007. FAH was determined in 41 patients (28 males and 13 females) by July 2023. Results: 41 patients started treatment at an average age of 9.1 years and continued for 6.5 years. The mean initial height was -2.6 standard deviation scores (SDS) and the mean FAH was -0.6 SDS. GH treatment was initiated at a significantly younger age in females than in males (7.2±1.9 vs 10.0±3.2; p=0.01). The mean FAH was 169.9±4.5cm for males and 156.1±3.2cm for females. Differences between initial height and final height SDS were not significant between males and females. The mean of FAH SDS was higher compared to their mid-parental height -1.0 SDS (p=0.017). In multiple regression analysis, FAH showed a positive correlation with initial height, duration of treatment, and growth rate in the first year of treatment, and a negative correlation with BMI SDS at the start of GH (r2=0.59; p=0.000). FAH SDS was positively related to initial height SDS and growth rate in the first year of treatment. (r2=0.3; p=0.001) Conclusions: The mean FAH SDS after GH treatment was significantly higher than the mean MPH SDS in IGHD patients. Moreover, the good response of GH treatment was associated with longer treatment duration, greater height at the start of treatment, better treatment response at 1 year, and lower initial BMI SDS. Presentation: 6/3/2024

Growth and Treatment in Congenital Adrenal Hyperplasia: An Observational Study from Diagnosis to Final Height

Introduction: Congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase deficiency results in inadequate cortisol and aldosterone synthesis and concomitant overproduction of adrenal androgens. Despite adequate replacement, impaired growth and overweight remain a clinical challenge. The main objective was to investigate the differences in growth, final height (FH), and body mass index (BMI) between different CYP21A2 genotype groups and glucocorticoid treatment strategies during the different phases of growth. Methods: This is a population-based observational cohort study from diagnosis to FH. A total of 86 subjects were diagnosed with CAH in Sweden during 1989–1994. Eighty subjects were followed until FH. There were no interventions apart from the clinical standard of care treatment for CAH. The main outcome measure was the corrected FH standard deviation score (cFH SDS) and its correlation with genotype, accumulated total glucocorticoid dose, and treatment strategy. In addition, BMI and growth trajectories during infancy, childhood, and adolescence were studied. Results: FH was shorter in patients with the more severe CYP21A2 genotypes. Treatment doses of glucocorticoid were within the international treatment recommendations (10–15 mg/m2). Patients with the null and I2 splice genotypes lost approximately 1 SD in FH, whereas patients with the milder genotypes (I172N, P30L, and V281L) were within 0.5 to 0 SDS from target height. cFH SDS was negatively affected by the use of prednisolone but did not correlate with overall glucocorticoid treatment dose calculated as hydrocortisone equivalents. BMI at 18 years was higher in patients treated with prednisolone but did not correlate with genotype. Conclusions: Corrected FH was more affected in patients with severe CYP21A2 genotypes. The addition of a low dose of prednisolone to the hydrocortisone treatment, despite an equivalent total dose of glucocorticoids, was associated with shorter FH and higher BMI in growing subjects with CAH.

A meta-analysis of combination therapy with gonadotrophin-releasing hormone agonist and growth hormone for children with idiopathic short stature and normal timed puberty.

The aim of this meta-analysis is to evaluate whether the combination therapy with gonadotrophin-releasing hormone agonist (GnRHa) and recombinant human growth hormone (rhGH) are effective in the treatment of children with idiopathic short stature (ISS) and normal timed puberty by interrogating data from clinical controlled trials. Literature retrieval, trail selection, data abstraction and quality assessment were completed independently by two authors. STATA software (version 14.1) was used for data analyses. This meta-analysis was conducted based on 8 (4 randomized and 4 non-randomized) controlled trials. A total of 245 ISS children with normal timed puberty were financially analyzed. Overall, combination therapy with GnRHa and rhGH can slightly increase final height by 3.70 and 3.43 cm compared with GH treatment alone and no treatment, final height standard deviation score (FHSDS) by 0.10 and 0.22, final height minus predicted adult height (FH-PAH) by 1.5 and 5.32 cm, final height minus predicted adult height (FH-TH) by 7.70 and 4.32 cm, respectively. Subgroup and meta-regression analyses revealed that study type, sample size, GnRHa duration, and percentage of boys were potential sources of between-trial heterogeneity. There was a low probability of publication bias for above comparisons, as indicated by Egger's tests. Our meta-analytical findings indicate that the combination therapy with GnRHa and rhGH can slightly increase the final height of ISS children with normal timed puberty, and the effect was not more obvious than GH alone. We do not recommend the combination therapy as a routine treatment for ISS. CRD42019133438.

Good glycemic control at puberty in boys with type 1 diabetes is important for final height.

Poor glycemic control in children with type 1 diabetes (T1D) may hinder sexual development and the associated growth spurt. This study aims to identify factors that may affect the timing of puberty, total pubertal growth (TPG), and final height (F-Ht) in boys with T1D. This was a retrospective longitudinal study of 68 boys diagnosed with T1D during 1996 to 2009, who were prepubertal at diagnosis and had completed puberty at the time of data collection. Data were accessed regarding anthropometric measurements, Tanner stage, and glycosylated hemoglobin (HbA1c) levels from diagnosis to F-Ht. F-Ht was compared to parental height and Israeli National Health Survey data. The mean F-Ht standard deviation score (F-Ht-SDS) was lower than the mean Ht-SDS at diagnosis (P< .006) but similar to the mean target height SDS (P= .3) and to values from the national survey (P= .12). Mean HbA1c levels in the year preceding pubertal onset were associated with the age at onset of puberty (R= 0.33, P= .009) and inversely with TPG (R= -0.3, P= .03). Mean HbA1c levels during puberty were inversely associated with TPG (R= -0.26, P= .035) and F-Ht (R= -0.28, P= .02). Boys who presented with diabetic ketoacidosis at diagnosis were shorter than those who did not throughout the follow-up. We found associations of age of pubertal onset, pubertal growth spurt, and F-Ht with target height and glycemic control before and during puberty. Targeted interventions to achieve optimal metabolic control during these time periods are needed for normal, timely puberty and for achieving optimal adult height within the genetic target height.

Longitudinal growth patterns and final height in childhood-onset systemic lupus erythematosus.

Patients with childhood-onset systemic lupus erythematosus (cSLE) are at risk of becoming short adults. To evaluate the growth patterns and risk factors of short final height, a retrospective study was conducted in 97 patients (87 females, 90%) with cSLE who grew from the time of diagnosis and reached their final height. The primary outcome was the final height. Participants were divided into participants with short final height (final height standard deviation score (HSDS) < - 2, n = 22, 23%) and participants with normal final height (final HSDS ≥ - 2, n = 75, 77%). At diagnosis, the mean age was 11.3 ± 2.4 years and HSDS was - 0.5 ± 1.3. The participants reached the final height of 1.51 ± 0.08 m (final HSDS - 1.3 ± 0.1) at mean age of 16.2 ± 2.3 years. The HSDS of participants with short final height steadily declined throughout the course of SLE (p = 0.02), and were significantly lower than participants with normal final height at any time point (p < 0.001). In participants with normal final height, HSDS significantly declined from baseline until 2 years after diagnosis (p = 0.01), and then became stable thereafter. The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.Conclusion: A substantial number of the participants with cSLE became short adults. Adequate nutrition and corticosteroid minimization should be emphasized in patients at high risk for short final height. What is known? • Growth failure is common in SLE due to many risk factors including chronic inflammation, malnutrition, and long-term use of corticosteroids. • In comparison to growth failure, final height is a better indicator of growth as the prevalence of growth failure is variable depending on definitions, patient age and pubertal status. What is new? • Nearly one fourth of children with SLE have short final height. • The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.

Final Height of Patients Who Underwent Bone Marrow Transplantation for Hematological Disorders During Childhood: A Study by the Working Party for Late Effects-EBMT

AbstractFew data are available on the long-term effect of bone marrow transplantation (BMT) on growth. This study examines those factors that play a role in the final height outcome of patients who underwent BMT during childhood. Data on 181 of 230 patients with aplastic anemia, leukemias, and lymphomas who had BMT before puberty (mean age, 9.8 ± 2.6 years) and who had reached their final height were analyzed. An overall decrease in final height standard deviation score (SDS) value was found compared with the height at BMT (P < 107) and with the genetic height (P < 107). Girls did better than boys, and the younger in age the person was at time of BMT, the greater the loss in height. Previous cranial irradiation + single-dose total body irradiation (TBI) caused the greatest negative effect on final height achievement (P < 104). Fractionation of TBI reduces this effect significantly and conditioning with busulfan and cyclophosphamide seems to eliminate it. The type of transplantation, graft-versus-host disease, growth hormone, or steroid treatment did not influence final height. Irradiation, male gender and young age at BMT were found to be major factors for long-term height loss. Nevertheless, the majority of patients (140/181) have reached adult height within the normal range of the general population.

Clinical benefits of sex steroids given as a priming prior to GH provocative test or as a growth-promoting therapy in peripubertal growth delays: Results of a retrospective study among ENDO-ERN centres.

Sex steroids, administered as a priming before GH stimulation tests (GHST) to differentiate between growth hormone deficiency (GHD) and constitutional delay of growth and puberty (CDGP) or as growth-promoting therapy using low-dose sex steroids (LDSS) in CDGP, are much debated. We aimed to compare auxological outcomes of CDGP or GHD children undergoing primed or unprimed GHST and to evaluate LDSS treatment in CDGP. Retrospective study among three paediatric University Hospitals in Italy and UK. 184 children (72 females) aged 12.4±2.08years underwent primed (/P+ ) or unprimed (/P- ) GHST and were followed up until final height (FH). CDGP patients were untreated (CDG P- ) or received LDSS (CDGP+ ). The cohort included 34 CDG P- /P+ , 12 CDGP+ /P+ , 51 GHD/P+ , 29 CDG P- /P- , 2 CDGP+ /P- and 56 GHD/P- . FH standard deviation score (SDS), Δ SDS FH-target height (TH) and degree of success (-1≤Δ SDS FH-SDS TH ≤ +1) were outcomes of interest. GHD/P+ had better FH-SDS (-0.87 vs -1.49; P=.023) and ΔSDS FH-TH (-0.35 vs -0.77; P=.002) than CDGP- /P+ . Overall, GHD/P+ showed the highest degree of success (90%, P=.006). Regardless of priming, both rhGH and LDSS improved degree of success compared to no treatment (89% and 86% vs 63%, P=.0009). GHD/P+ showed a trend towards a higher proportion of permanent GHD compared to GHD/P- (30.43% vs 15.09%; P=.067). In peripubertal children, priming before GHST improves diagnostic accuracy of GHST for idiopathic GHD. LDSS treatment improves auxological outcomes in CDGP.

Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: Eleven years of observation

It is held that enzyme replacement therapy (ERT) accelerates the growth rate in children with Gaucher disease, but its effect on final height has not been established with certainty. This study presents final heights of Gaucher patients followed up for 15 years.The study included 41 adults with non-neuronopathic Gaucher disease. The final height of the patients and age at puberty was compared to their mid-parental target height and to their siblings' heights.Mean final height standard deviation score (HSDS) in the patients was − 0.22, but none of the patients was abnormally short (HSDS of less than − 2.2). Mean age at menarche of the female patients (14.7 years) was significantly delayed compared to that of their mothers (P = 0.0005), and mean age at first shaving in the boys was 16 years.Our study showed that the mean final height of Gaucher patients fell below the mean of the 2000 CDC growth charts, but the patients were not of short stature (height less than the 3rd percentile). ERT treatment did not significantly impact the mean final HSDS. The onset of puberty, as indicated by the age at menarche, was delayed in girls with Gaucher disease.

Long-term follow-up of children with classic congenital adrenal hyperplasia: suggestions for age dependent treatment in childhood and puberty.

Background In congenital adrenal hyperplasia (CAH), achieving the balance between overtreatment and undertreatment remains challenging. Final height (FH) can serve as a long-term outcome measure. We aimed to identify age-dependent factors that influence FH in CAH patients, resulting in age-specific treatment goals. Methods We retrospectively evaluated longitudinal data of 39 pediatric CAH patients born between 1980 and 1997 from the Radboudumc CAH database. We analyzed height and bone age (BA) at diagnosis or 4 years of age, at the start of puberty and at FH. Height data were corrected for parental height and secular trend. Hydrocortisone (HC) use and salivary steroid concentrations were studied longitudinally throughout childhood and puberty. Results Median FH standard deviation scores (SDSs) corrected for target height SDSs (THSDSs) was -1.63. Median height SDS corrected for THSDS (HSDS-THSDS) decreased from diagnosis/age 4 years to FH in both salt wasting (SW) CAH and simple virilizing (SV) CAH, and in both male and female patients. However, when height was corrected for BA, no height loss occurred from diagnosis/age 4 years to FH in any of the subgroups, while a height gain was seen in SV males. In the combined model analyzing both HC dose and salivary steroid concentrations, in childhood the androstenedione (A) concentration was negatively associated with FH, while in puberty the HC dose was negatively associated with FH. Conclusions In CAH, loss of growth potential already occurs in early childhood. In prepubertal children, exposure to elevated androgens is associated with decreased FH. In puberty, the growth suppressing effects of HC outweigh the negative effects of elevated androgens. Therefore, we suggest different treatment approaches in prepubertal and pubertal patients.

The Gonadotropin-Releasing Hormone Analogue Therapy May Not Impact Final Height in Precocious Puberty of Girls With Onset of Puberty Aged 6 - 8 Years.

BackgroundThe effect on final height of gonadotropin-releasing hormone analogues (GnRHa) used in the treatment of precocious puberty is controversial. The aim of this study was to determine whether or not GnRHa therapy would make any contribution to final height in precocious puberty of girls with onset of pubertal characteristic development aged 6 - 8 years.MethodsAge at start of puberty, target height standard deviation score (SDS) presentation, follow-up height SDS, body mass index (BMI) SDS, bone age and predicted adult height of 34 female subjects who had reached their final height and with pubertal findings beginning at the ages of 6 - 8 were evaluated. These subjects were divided into two groups: treatment and non-treatment groups. The treatment group was further divided into two subgroups, receiving monthly or three-monthly depot GnRHa.ResultsAge at onset of puberty was 7.2 ± 0.9 years. Twenty-five cases were started on GnRHa and nine were followed-up without treatment. Fourteen cases received monthly 3.75 mg depot triptorelin acetate and 11 received three-monthly 11.25 mg depot. Mean age at start of treatment in the treatment group was 9.1 ± 1.2 years and mean bone age was 9.7 ± 2.3 years. Age at presentation in the non-treatment group was 8.4 ± 1.4 years and bone age was 10.3 ± 2.1 years. Target and final height SDS were similar in all the groups (P > 0.05). No difference was determined between the treatment groups in terms of initial height SDS, bone age, length of treatment, final height SDS or BMI SDS (P > 0.05).ConclusionsGnRHa therapy did not make a positive contribution to final height in precocious puberty of girls with onset of puberty aged 6 - 8 years.

Long-term Growth in Congenital Adrenal Hyperplasia.

To retrospectively assess growth of children with congenital adrenal hyperplasia (CAH) with special reference to puberty and to assess longitudinal growth and final height of subset of children with CAH. A retrospective analysis of 30 children (14 boys) with classic CAH (11 salt wasters, 19 simple virilisers) followed up for a mean duration of 9.9 ± 2.4 y (Study period December 2002 through December 2016) was performed. Height Z scores, target height Z scores, height velocities and laboratory parameters were analysed. Children were treated with hydrocortisone in a mean dose of 15.7 ± 3.3mg/m2/d. Mean 17-hydroxy progesterone in boys and girls were 10.8 ± 6.7ng/ml and 11.3 ± 9.3ng/ml respectively. Fifteen children (7 boys) developed central precocious puberty at mean age of 7.6 ± 1.8 y and 13 were treated with GnRH analogues for 3.5 y. Of all patients, 18 (10 girls, 8 boys) reached final height at a mean age of 14.2 ± 1.6 y. Mean final height achieved was 158.0 ± 8.5cm in boys [target height (TH) -165.5 ± 3.8cm] and in girls it was 149.9 ± 6.7cm [target height (TH) 154.7 ± 6.4cm]. Final height standard deviation scores (SDS) for boys and girls were - 2.06 ± 1.1 (TH-SDS -1.06 ± 0.5) and - 1.47 ± 1.1 (TH-SDS -0.56 ± 1.2) respectively and were not significantly different from target height Z scores (p > 0.05). Growth velocity was attenuated during pubertal years. Monitoring growth and puberty in children with CAH is critical for optimizing final height.

Improved final predicted height with the injection of leuprolide in children with earlier puberty: A retrospective cohort study.

The adult height of children with early onset puberty is limited by the premature maturation of hypothalamic-pituitary-gonadal axis. To evaluate the effects of gonadotropin-releasing hormone analog (GnRHa) treatment on the final height (FH) and bone maturation rate (BMR) in girls with early puberty (EP) or idiopathic central precocious puberty (ICPP), we examined data from girls who were diagnosed with EP or ICPP and underwent GnRHa (Leuplin Depot: 3.75 mg/month) at China Medical University Hospital, in Taiwan, between 2006 and 2015. Patients were observed until the achievement of FH and divided into an “EP group” (T-ep) and “ICPP group” (T-icpp) according to the age of onset of puberty. Eighty-seven patients were enrolled (T-ep, N = 44, puberty onset at 8–10 years; T-icpp, N = 43, puberty onset before 8 years). The demographic data of girls with EP or IPP was characterized. BMR, change in predicted final height (PFH) after GnRHa treatment, target height (TH) and FH were measured. After GnRHa treatment, the study groups (T-ep: 160.24±6.18 cm, T-icpp: 158.99±5.92 cm) both had higher PFH than at initiation (T-ep: 159.83±7.19 cm, T-icpp: 158.58±5.93 cm). There was deceleration of BMR in both groups (T-ep: 0.57±0.39; T-icpp: 0.97±0.97) and a significant difference between the groups (p = 0.027). The gap in FH standard deviation scores (SDS) and TH SDS had a significant difference in T-ep (p = 0.045) but not in T-icpp. Moreover, there was no difference in the gap of PFH SDS between the 1st and final treatment in both groups. We concluded that GnRHa decelerated BMR in girls with earlier puberty. Further prospective clinical studies are warranted.

Hydrocortisone Therapy and Growth Trajectory in Children with Classical Congenital Adrenal Hyperplasia

Poor linear growth is one of the main concerns in children with congenital adrenal hyperplasia (CAH). We aimed to analyze factors affecting growth trajectory in children with classical CAH. Clinical records of children followed from infancy up to the end of growth at two Italian tertiary referral hospitals were reviewed. Fifty-seven patients (31 males), treated with hydrocortisone and fludrocortisone only, were included. Clinical observations were divided into three groups: 0 to 2 years, 172 observations; from 2 years to puberty onset, 813 observations; after puberty onset, 527 observations. Height velocity, pubertal growth spurt, and final height were evaluated as outcomes. Final height standard deviation score (SDS) was lower than target height SDS (-0.74 ± 1.1 versus -0.31 ± 1.01; P<.001). Target-adjusted final height SDS was -0.44 ± 1.8 in males and -0.13 ± 1.1 in females (P = .001). Total pubertal growth was 21.9 ± 7.3 cm in males and 19.2 ± 8.2 cm in females (P = .19). Hydrocortisone dose increased and height-velocity SDS decreased during puberty. At multivariable analysis, height-velocity SDS was adversely affected by hydrocortisone dose (P = .038) and directly related to adrenocorticotropic hormone (ACTH) levels (P = .023). Target-adjusted final-height SDS was adversely affected by hydrocortisone dose (P<.001) and positively related to mineralocorticoid therapy (P = .001) and ACTH levels (P = .02). Total pubertal growth (cm) was positively related to ACTH levels (P = .01). Height outcome of CAH patients is now better than previously reported. During puberty, the lowest effective dose of hydrocortisone should be used to optimize pubertal growth spurt and final height. 17-OHP = 17-alpha-hydroxyprogesterone ACTH = adrenocorticotropic hormone BMI = body mass index CAH = congenital adrenal hyperplasia GH = growth hormone HPA = hypothalamus-pituitary-adrenal PRA = plasma renin activity SDS = standard deviation score SV = simple virilizing SW = salt-wasting.

Growth and final height of children with Gaucher disease: A 15-year follow-up at an Israeli Gaucher center

BackgroundIt is held that enzyme replacement therapy (ERT) accelerates the growth rate in children with Gaucher disease, but its effect on final height has not been established with certainty. This study presents final heights of Gaucher patients followed up for 15years. MethodsThe study included 41 adults with non-neuronopathic Gaucher disease. The final height of the patients and age at puberty was compared to their mid-parental target height and to their siblings' heights. ResultsMean final height standard deviation score (HSDS) in the patients was −0.22, but none of the patients was abnormally short (HSDS of less than −2.2). Mean age at menarche of the female patients (14.7years) was significantly delayed compared to that of their mothers (P=0.0005), and mean age at first shaving in the boys was 16years. ConclusionOur study showed that the mean final height of Gaucher patients fell below the mean of the 2000 CDC growth charts, but the patients were not of short stature (height less than the 3rd percentile). ERT treatment did not significantly impact the mean final HSDS. The onset of puberty, as indicated by the age at menarche, was delayed in girls with Gaucher disease.

Gonadotropin-Releasing Hormone Analogue Treatment in Females with Moderately Early Puberty: No Effect on Final Height

Objective: To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age.Methods: Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height.Results: Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold.Conclusion: We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty.

Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study.

PurposeWe examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment.MethodsWe studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients.ResultsThe diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6–3.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27–2.73) for patients with organic GHD (n = 18) and 1.19 (0.97–1.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 (−0.03 to 0.77, n = 13). Final height SDS was >−2 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD.ConclusionsData from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases.

Seguridad y efectividad del tratamiento con hormona de crecimiento: estudio GeNeSIS en España

IntroductionCountry-specific information on pediatric GH therapy is available from multi-national studies. MethodsA total of 1294 children in Spain enrolled in the observational Genetics and Neuroendocrinology of Short-stature International Study (GeNeSIS). Adverse events were assessed in all GH-treated patients (n=1267) and effectiveness in those with GH deficiency (GHD, 78%). ResultsMean age at time of entry to the study was 9.8 years. GH was initiated at a median (Q1-Q3) 0.22 (0.20−0.25) mg/kg/week and administered for 2.8 (1.6-4.4) years. For 262 patients with GHD and 4-year data, mean (95% CI) height velocity was 4.3 (4.1 - 4.6) cm/year at baseline, 9.0 (8.7 to 9.4) cm/year at 1-year, and 5.5 (5.2 to 5.8) cm/year at 4-years. Height standard deviation score (SDS) was —2.48 (—2.58 to —2.38) at baseline and -1.18 (—1.28 to —1.08) at 4 years. Final height SDS minus target height SDS (n=241) was −0.09 (−0.20 to 0.02). In 1143 GH-treated patients with ≥1 year follow-up, 93 (8.1%) reported treatment-emergent adverse events. Serious events were reported for 7 children, with 2 considered GH-related. ConclusionThese data confirm the benefit of GH replacement therapy on height gain for the patients in Spain. The safety profile was consistent with that already known for GH therapy.

Considerable variations in growth hormone policy and prescription in paediatric end-stage renal disease across European countries-a report from the ESPN/ERA-EDTA registry.

Growth retardation in paediatric end-stage renal disease (ESRD) has a serious impact on adult life. It is potentially treatable with recombinant growth hormone (rGH). In this study, we aimed to quantify the variation in rGH policies and actual provided care in these patients across Europe. Renal registry representatives of 38 European countries received a structured questionnaire on rGH policy. Cross-sectional data on height and actual use of rGH on children with ESRD aged <18 years were retrieved from the ESPN/ERA-EDTA Registry. In 21 (75%) of 28 responding countries, rGH is reimbursed for children with ESRD. The specific conditions for reimbursement (minimum age, maximum age and chronic kidney disease stage) vary considerably. Mean height standard deviation scores (SDS) at renal replacement therapy (RRT) [95% confidence interval (CI)] were significantly higher in countries where rGH was reimbursed -1.80 (-2.06; -1.53) compared with countries in which it was not reimbursed [-2.34 (-2.49;-2.18), P < 0.001]. Comparison of the mean height SDS at onset of RRT and final height SDS yielded similar results. Among the 13 countries for which both data on actual rGH use between 2007 and 2011 and data from the questionnaire were available, 30.1% of dialysis and 42.3% of transplanted patients had a short stature, while only 24.1 and 7.6% of those short children used rGH, respectively. Reimbursement of rGH associates with a less compromised final stature of ESRD children. In many countries with full rGH reimbursement, the actual rGH prescription in growth-retarded ESRD children is low and obviously more determined by the doctor's and patients' attitude towards rGH therapy than by financial hurdles.

Gonadotropin releasing hormone agonist treatment to increase final stature in children with precocious puberty: a meta-analysis.

In the setting of central precocious puberty (CPP), the motivation for hormonal intervention is to help the child to reach a taller adult stature than she would achieve otherwise. While gonadotropin-releasing hormone analogs (GnRHa) constitute an established treatment for improving adult stature in girls presenting with CPP up to age 6 (true precocious puberty), it is not yet clear whether or not the same is true in the setting of CPP presented in girls beyond age 6 (advance puberty). GnRHa may slow growth velocity, offsetting the anticipated improvement in final height that should have resulted from the increased time before growth plate fusion. Consequently, it's been suggested that growth hormone (GH) should be combined with GnRHa to improve the results.Few controlled prospective studies have been performed with GnRHa in children and many conclusions rely in part on collective expert opinion. Therefore, the literature was searched and relevant studies were selected using the search terms “gonadotropin releasing hormone agonist,” “precocious puberty/early puberty,” and “GnRH analogue.” After selected articles were screened for relevance, the process yielded 8 studies, the results of which were then pooled in a meta-analysis aimed at evaluating the effects of GnRHa therapy both with and without added GH in the setting of early puberty.A significant difference was elucidated in final height and predicted adult height comparing GnRHa and combined GnRHa/GH groups. However, no significant difference was elucidated in final height standard deviation scores (SDS) and initial height SDS when comparing GnRHa and control groups. At the same time, the final analysis revealed no significant difference in final height SDS and initial height SDS when GnRHa and combined GnRHa/GH groups were compared.The results suggest GnRHa therapy may have a positive effect on final adult height in girls with early puberty, while adding GH to the treatment may suggest more advantage. Interpretation of the results requires extreme caution, given the complexity of the outcome analysis. Final height gain may prove to be a more appropriate measure of treatment efficacy in any case.