Change In Standard Deviation Score Research Articles

Girls with idiopathic central precocious puberty did not display substatial changes in body mass index after treatment with gonadotropin-releasing hormone analogues.

To evaluate changes in body mass index (BMI) in girls during and after treatment for idiopathic central precocious puberty (iCPP). We studied 123 girls receiving gonadotropin-releasing hormone analogue (GnRHa)treatment for iCPP from 2009 to 2019. Pubertal and anthropometric measurements were monitored at routine clinical visits. BMI standard deviation scores (SDS) were estimated at baseline and followed in two stages from baseline to end of treatment (median 18.9 months) and from end of treatment to end of follow-up (median 18.2 months). The influence of baseline BMI SDS and the frequency and dose of treatment was evaluated using BMI trajectories and latent class mixed models. The median age at treatment initiation was 8.5 years. The median BMI SDS at baseline was 0.7, corresponding to a median BMI of 17.4 kg/m2 . Overall, no changes in BMI SDS were observed during treatment. According to baseline BMI subgroups, an increasing trend in BMI trajectories during treatment was observed for girls in the lowest BMI group. After treatment, most girls maintained stable BMI levels. Our retrospective study did not provide evidence that GnRHa treatment for iCPP had a significant impact on BMI trajectories in girls.

Imatinib treatment and longitudinal growth in pediatric patients with chronic myeloid leukemia: Influence of demographic, pharmacological, and genetic factors in the German CML-PAED cohort.

In children and adolescents, impaired growth due to tyrosine kinase inhibitor therapy remains an insufficiently studied adverse effect. This study examines demographic, pharmacological, and genetic factors associated with impaired longitudinal growth in a uniform pediatric cohort treated with imatinib. We analyzed 94 pediatric patients with chronic myeloid leukemia (CML) diagnosed in the chronic phase and treated with imatinib for >12 months who participated in the Germany-wide CML-PAEDII study between February 2006 and February 2021. During imatinib treatment, significant height reduction occurred, with medians of -0.35 standard deviation score (SDS) at 12 months and -0.76 SDS at 24 months. Cumulative height SDS change (Δheight SDS) showed a more pronounced effect in prepubertal patients during the first year but were similar between prepubertal and pubertal subgroups by the second year (-0.55 vs. -0.50). From months 12 to 18 on imatinib, only 18% patients achieved individually longitudinal growth adequate to the growth standard (Δheight SDS≥0). When patients were divided into two subgroups based on median Δheight SDS (classifier Δheight SDS > or ≤-0.37) after one year on imatinib therapy, cohort 1 (Δheight SDS extending -0.37) showed younger age at diagnosis, a higher proportion of prepubertal children, but also better treatment response and higher imatinib serum levels. Exploring the association of growth parameters with pharmacokinetically relevant single nucleotide polymorphisms, known for affecting imatinib response, showed no correlation. This retrospective study provides new insights into imatinib-related growth impairment. We emphasize the importance of optimizing treatment strategies for pediatric patients to realize their maximum growth potential.

Effects of early recombinant human growth hormone treatment in young Chinese children with Prader–Willi syndrome

BackgroundPrader–Willi syndrome (PWS) is a rare and multisystemic genetic disorder that is characterized by severe hypotonia, hyperphagia, short stature, and global developmental delay. Although early recombinant human growth hormone (rhGH) treatment has been proven to rescue some symptoms and bring additional benefits to PWS patients, studies in patients under 2 years old are scarce. Thus, this study aims to investigate the effectiveness and safety of rhGH treatment for young children.MethodsA total of 96 genetically confirmed Chinese PWS infants or toddlers (47 males) followed between 2013 and 2022 were retrospectively analyzed. Sixty-five infants (early treatment group) started rhGH treatment during their first year, and 31 toddlers (later treatment group) started at the age of 1–2 years. Auxological parameters, carbohydrate metabolism parameters, thyroid function, liver function, insulin-like growth factor-1 (IGF-1), and radiographs were acquired before the initiation of the treatment and every 3–6 months thereafter. Height/length, weight, and weight for height were expressed as standard deviation scores (SDSs) according to WHO child growth standards.ResultsThe mean SDS of length/height in the early treatment group was significantly higher than that in the later treatment group throughout the observation period (all P < 0.001). The change in the length SDS between the two groups at 1 year old and 4 years old was 1.50 (95% CI, 0.88–2.13) and 0.63 (95% CI, 0.16–1.10), respectively. Compared to the later treatment group, the weight SDS in the early treatment group increased by 0.94 (95% CI, 0.37–1.52) at 1 year old and 0.84 (95% CI, 0.28–1.39) at 2 years old. No statistical significance was found after 2.5 years of age. No significant differences were observed in IGF-1, incidence of liver dysfunction, hypothyroidism or spinal deformity between the two groups.ConclusionsrhGH treatment improved growth and body composition in infants and toddlers. Furthermore, an early start of rhGH treatment is expected to have more efficacy than the later treatment group without an increase in adverse effects.

RF26 | PMON334 Once-Weekly Somapacitan in Growth Hormone Deficiency: 4-Year Efficacy and Safety Results from REAL 3, a Randomised Controlled Phase 2 Trial

Abstract The current treatment for growth hormone deficiency (GHD) requires daily subcutaneous injections, which can be burdensome. Somapacitan is a long-acting growth hormone (GH) derivative in development for once-weekly use in children with GHD. REAL 3 (NCT02616562) is an ongoing, phase 2, multinational, randomised, open-label, controlled trial designed to investigate the efficacy and safety of somapacitan compared with daily GH (Norditropin®). Prepubertal children with GHD who were naïve to GH treatment received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/week (n=14) somapacitan, or daily GH 0.034 mg/kg/day (equivalent to 0.238 mg/kg/week; n=14) for 1 year. This was followed by a 2-year safety extension, in which all patients on somapacitan (n=45) received 0.16 mg/kg/week, while patients receiving daily GH remained on daily GH. In a further, ongoing 4-year long-term safety extension, patients treated with somapacitan remained on somapacitan (somapacitan/somapacitan, n=39) and all patients on daily GH switched to somapacitan 0.16 mg/kg/week (daily GH/somapacitan, n=11). Here, we present efficacy and safety results from the first year of the 4-year long-term safety extension. At year 4, the mean (SD) height velocity (HV) was 7.4 (1.6) cm/year for the somapacitan/somapacitan group and 6.6 (1.6) cm/year for the daily GH/somapacitan group, compared with 8.3 (1.7) and 7.6 (2.0) cm/year for the somapacitan/somapacitan and daily GH groups, respectively, at year 3. The mean (SD) HV standard deviation score (SDS) was 1.55 (1.70) for the somapacitan/somapacitan group and 0.88 (1.61) for the daily GH/somapacitan group, and the mean (SD) change in height SDS from baseline was 2.85 (1.25) and 2.28 (0.97), respectively. The mean (SD) insulin-like growth factor-I SDS at year 4 was 1.29 (1.23) and 0.94 (1.60) for the somapacitan/somapacitan and daily GH/somapacitan groups, respectively. During year 4, 20 patients (51.3%) experienced 84 adverse events (AEs) in the somapacitan/somapacitan group, and eight patients (72.7%) experienced 12 AEs in the daily GH/somapacitan group. The most common AE was nasopharyngitis, occurring in four patients (10.3%) in the somapacitan/somapacitan group and one patient (9.1%) in the daily GH/somapacitan group; all other AEs occurred in &amp;lt;10% of patients in either group. Most AEs were mild or moderate and unlikely related to GH treatment. One severe AE (surgery for elbow fracture) occurred in the somapacitan/somapacitan group. No serious AEs were reported in year 4. Since previously reported in year 3, one patient in the somapacitan/somapacitan group experienced five injection-site reactions; none occurred in the daily GH/somapacitan group. In conclusion, these year 4 data support the efficacy and safety results of somapacitan observed in the previous 3 years of the trial. In year 4, height-related outcomes were similar for patients who continued treatment with somapacitan and those who switched from daily GH to somapacitan. Somapacitan was well tolerated, and no safety signals were identified. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:44 p.m. - 12:49 p.m.

Changes in body mass index during treatment of childhood acute lymphoblastic leukemia with the Nordic ALL2008 protocol.

Children with acute lymphoblastic leukemia (ALL) have a tendency to gain weight during treatment. As overweight and obesity associate with health problems, prophylactic interventions are warranted. Therefore, it is important to identify the children most prone to gain weight. Patients aged 2.0-17.9 years at ALL diagnosis were identified from the NOPHO ALL2008 registry. Registry data was complemented with height and weight at the end of therapy from questionnaires. Body mass index (BMI) was classified according to international age- and sex-adjusted International Obesity Task Force BMI cut-offs. BMI values were transformed into standard deviation scores (SDS) to calculate the difference in BMISDS during treatment. Data on BMI change were available for 765 children. Overweight and obesity doubled during treatment: 9.7% were overweight and 2.1% obese at diagnosis and 21.8% and 5.4% at the end of therapy, respectively. The mean BMISDS change was +0.64. Younger (2.0-5.9 years) and healthy weight children were most prone to become overweight (mean change in BMI SDS +0.85 and +0.65, respectively). Younger children (2.0-5.9 years) with healthy weight at diagnosis were most prone to becoming overweight and therefore are an important group to target while considering interventions.

Short-term effect of growth hormone treatment in childhood leukemia survivors with growth hormone deficiency.

Survivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment. A total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population. Of the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment. GH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.

Growth and Nutritional Outcomes in Children Post-Haematopoietic Stem Cell Transplant without Exposure to Total Body Irradiation

AimsPoor growth in childhood cancer survivors who undergo haematopoietic stem cell transplant (HSCT) without exposure to radiation is reported anecdotally, although literature to support this is limited. The aims of this study were to assess the change in height standard deviation score (SDS) and the final adult height (FAH) in children who underwent chemotherapy-only conditioned HSCT and to identify predictors of poor growth. Materials and methodsWe conducted a retrospective hospital medical record review (1984–2010) of children (1–10 years) who underwent chemotherapy-only conditioned HSCT, noting anthropology measurements at cancer diagnosis, HSCT, 10 years old and FAH. ResultsThe median age at HSCT of the 53 patients was 4.5 years, 75% had a haematological malignancy and 25% a solid tumour. Half of the cohort underwent allogenic HSCT and most (89%) conditioned with busulphan. The mean change in height SDS from primary cancer diagnosis to FAH was –1.21 (±1.18 SD), equivalent to 7–8.5 cm loss, with a mean FAH of –0.91 SDS (±1.10 SD). The greatest height loss occurred between diagnosis and HSCT (–0.77 SDS, 95% confidence interval –1.42, –0.12, P = 0.01), with no catch-up growth seen by FAH. Patients with solid tumours had the greatest height loss. Overall body mass index SDS did not change significantly over time, or by cancer type. ConclusionsChemotherapy-only conditioned HSCT during childhood can impact FAH, with the greatest height loss occurring prior to HSCT and no catch-up growth after treatment finishes. Children transplanted for a solid tumour malignancy seem to be more at risk, possibly due to intensive treatment regimens, both pre-transplant and during conditioning.

A 4-hour Profile of 17-hydroxyprogesterone in Salt-wasting Congenital Adrenal Hyperplasia: Is the Serial Monitoring Strategy Worth the Effort?

Objective:Since there is no gold standard laboratory variable for adjustment of treatment in congenital adrenal hyperplasia (CAH), the aim was to assess the use of a 4-hour profile of serum 17-hydroxyprogesterone (17-OHP) to determine the most appropriate sample time and level of 17-OHP in predicting the metabolic control and evaluate the role of sex hormone-binding globulin (SHBG) in hyperandrogenemia.Methods:This study included children with salt-wasting CAH. Measurements for 17-OHP and cortisol were made from samples obtained before and 1, 2, and 4 hours after the morning dose of hydrocortisone. Patients were designated to have poor metabolic control when androstenedione levels according to age and sex-specific reference intervals were high and annual height standard deviation score (SDS) changes were ≥0.5.Results:The study cohort was 16 children (9 girls) with a median age of 7-years old. Premedication 17-OHP levels were strongly correlated with 17-OHP levels 1, 2, and 4 hours after the morning dose (rs=0.929, p<0.01; rs=0.943, p<0.01; rs=0.835, p<0.01, respectively). 17-OHP profiles (0, 1, 2, 4 hours) of poor (n=6) and good (n=10) metabolically controlled cases were similar. Among the patients with poor metabolic control, two cases had 17-OHP levels <2 ng/mL at all times. The remaining patients with poor metabolic control had median 17-OHP levels above 104 ng/mL, 82 ng/mL, 14 ng/mL, and 4 ng/mL, for baseline and 1, 2, and 4 hours, respectively. Differences between the poor and well-controlled group were androstenedione levels with respect to upper limit of normal [1.8 (1.5) and 0.5 (1.5) ng/mL, respectively p=0.03], annual change in height SDS [0.7 (0.2) and -0.03 (0.8) SDS, respectively, p=0.001], and daily hydrocortisone doses [7 (6) and 16 (8) mg/m2/day, respectively, p=0.02]. Androstenedione and SHBG levels were negatively correlated in the pubertal children (rs=-0.7, p=0.04).Conclusion:We conclude that: (i) a 4-hour 17-OHP profile is not useful in predicting hyperandrogenemia; (ii) suppressed levels of 17-OHP do not always indicate overtreatment; (iii) reference intervals of 17-OHP for different time periods might be of importance; (iv) low hydrocortisone doses should be avoided; and (v) SHBG could be used in pubertal children as an indicator of hyperandrogenemia.

P030 Impact of methotrexate on growth in children with Juvenile Idiopathic Arthritis

Abstract Background Juvenile idiopathic arthritis (JIA) is a heterogeneous group of chronic inflammatory disease which could be responsible for functional impairment and severe growth disturbance. Conventional disease-modifying antirheumatic drugs, such as methotrexate (MTX), may improve growth velocity especially by regulating systemic inflammation. The objective of this study was to evaluate the effect of MTX on growth parameters in pre-pubertal children with JIA and to determine the factors affecting the growth velocity. Methods We assessed height and changes in the height standard deviation score (SDS) at disease onset, at the onset of MTX and at the last follow-up visit in a cross-sectional study of JIA children. All patients were pre-pubertal when MTX began and were followed for at least 6 months afterward. We compared growth parameters (height, growth rate, weight and body mass index (BMI)) in responders and non-responders to MTX. The growth rate was defined as the number of millimeters of height acquired during 1 year. Associations between changes in the height SDS and discrete variables were evaluated using χ2 or Fisher’s exact tests. The significance level was set at 0.05. Results We enrolled 36 pre-pubertal children with JIA (34 boys and 12 girls) who had been treated with MTX orally. Median patient age was 6.2 years [4–13] at the onset of MTX and 8.4 years [6.1–14.9] at the latest follow-up. The median disease duration was 2.7 years [2.5–5.3]. Twenty-one patients (58.3%) had oligoarticular JIA, 2 patients (5.5%) had systemic JIA, 10 (27.7%) had polyarticular JIA and 3 (8.3%) had enthesitis-related arthritis. Nineteen children (52.7%) had received corticosteroids during an average period of 1.7 years [0.6–3] with a mean of 10 mg/day of prednisone or equivalent. The median duration of MTX at the latest follow-up was 3.1 years [0.62–5.5] with a mean MTX dose of 10 mg/m2/week [10–15]. Twenty-eight patients responded to MTX treatment and 8 did not. There were no significant differences between the responders and non-responders for age at treatment initiation, disease duration and mean MTX dose. At MTX onset, no significant differences between the two groups in terms of height (P = 0.52), growth rate (P = 0.08), weight (P = 0.74) and BMI (P = 0.9) were found. One year after MTX therapy, mean height (0.2 vs -1.1; P = 0.03), mean growth rate (0.5 vs –2.9 SDS; P = 0.01), mean weight (0.4 vs -2.3 SDS; P = 0.01) and mean BMI (0.6 vs -1.9; P = 0.04) were significantly higher in the responder group than in non responders, respectively. At the latest follow-up, this increase was significantly maintained for growth rate (P = 0.001) and height (P = 0.002) in the responder group. In the multivariate analysis, patients who required &amp;gt;10 mg/m2/week of MTX, systemic JIA and patients with reliance on steroids had a significantly lower growth velocity after the onset of MTX (P &amp;lt; 001, P = 0.02, P = 0.02 respectively). Conclusion In our study, the increase in growth parameters in pre-pubertal children with JIA was associated with a better control of the disease activity under MTX therapy.

Changes in height standard deviation scores during early life are affected by nutrition.

BackgroundLarge changes in height standard deviation score (SDS) have been reported from birth to 3 years of age. We analyzed how early these changes start and whether they are affected by nutrition.MethodsThe longitudinal growth of 1,849 children born between March 1 2007 and August 31 2007 or between March 1, 2009 and August 31 2009 with five records from birth to 3 years of age was analyzed.ResultsThe height SDS at birth was positively correlated with body mass index (BMI) SDS at birth (r = 0.224, P < 0.0001). The height SDS at birth decreased among children with a positive height SDS and increased among children with a negative height SDS. The changes occurred immediately after birth and became more modest as children aged. Regarding the change in the height SDS from birth to 3 years of age, 33.4% of children increased more than 0.5 SDs, 39.8% of children decreased more than 0.5 SDs, and 34.4% of children remained within ±0.5 SDs. The change in height SDS displayed a strong positive correlation with the change in weight during the four periods. From birth till 3 months, from 3 months till 6 months, from 6 months till 1.5 years, and from 1.5 years till 3 years.ConclusionsThe significant positive correlation between height SDS and BMI SDS suggests an effect of children’s nutrition status in utero. The height SDS change started immediately after birth and the change was largest from birth to 3 months. A positive correlation between changes in height SDS and weight suggest that growth during early childhood depends on nutritional status.

Effectiveness and Overall Safety of NutropinAq® for Growth Hormone Deficiency and Other Paediatric Growth Hormone Disorders: Completion of the International Cooperative Growth Study, NutropinAq® European Registry (iNCGS).

ObjectiveThe International Cooperative Growth Study, NutropinAq® European Registry (iNCGS) (NCT00455728) monitored long-term safety and effectiveness of recombinant human growth hormone (rhGH; NutropinAq® [somatropin]) in paediatric growth disorders.MethodsOpen-label, non-interventional, post-marketing surveillance study recruiting children with growth disorders. Endpoints included gain in height standard deviation score (SDS), adult height, and occurrence of adverse events (AEs).Results2792 patients were enrolled. 2082 patients (74.6%) had growth hormone deficiency (GHD), which was isolated idiopathic in 1825 patients (87.7%). Non-GHD diagnoses included Turner syndrome (TS) (n=199), chronic renal insufficiency (CRI) (n=10), other non-GHD (n=498), and missing data for three participants. Improvements from baseline height SDS occurred at all time points to Month 132, and in all subgroups by disease aetiology. At Month 12, mean (95% CI) change in height SDS by aetiology was: idiopathic GHD 0.63 (0.61;0.66), organic GHD 0.71 (0.62;0.80), TS 0.59 (0.53; 0.65), CRI 0.54 (-0.49;1.56), and other non-GHD 0.64 (0.59;0.69). Mean height ( ± SD) at the last visit among the 235 patients with adult or near-adult height recorded was 154.0 cm ( ± 8.0) for girls and 166.7 cm ( ± 8.0) for boys. The most frequent biological and clinical non-serious drug-related AEs were increased insulin-like growth factor concentrations (314 events) and injection site haematoma (99 events). Serious AEs related to rhGH according to investigators were reported (n=30); the most frequent were scoliosis (4 events), epiphysiolysis (3 events), and strabismus (2 events).ConclusionsThere was an improvement in mean height SDS in all aetiology subgroups after rhGH treatment. No new safety concerns were identified.

Once-Weekly Somapacitan Versus Daily Growth Hormone in Growth Hormone Deficiency: 2-Year Efficacy Results From REAL 3, a Randomized Phase 2 Trial

Abstract Current treatment for growth hormone (GH) deficiency (GHD) requires daily injections, which can be burdensome for the patients/caregivers. Once-weekly somapacitan is a long-acting GH derivative currently in phase 3 for use in children with GHD and phase 2 for short children born small for gestational age. A phase 2, multinational, randomized, open-label, controlled trial (NCT02616562) investigated the efficacy and safety of somapacitan in children compared with daily GH (Norditropin®). GH-treatment-naïve prepubertal children with GHD received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/week (n=14) subcutaneous (s.c.) somapacitan, or s.c. daily GH 0.034 mg/kg/day (0.24 mg/kg/week; n=14) for 52 weeks, followed by a 104-week safety extension. In the extension phase, all patients on somapacitan received 0.16 mg/kg/week; daily GH dose remained unaltered. The 52-week efficacy and safety results have been reported previously. We report here the efficacy results after 104 weeks of GH treatment. At week 104, mean (standard deviation [SD]) height velocity (HV) in the first year of the safety extension was: 10.6 (1.4), 10.0 (1.6) and 9.2 (1.7) cm/year for 0.04/0.16 mg/kg/week (n=13), 0.08/0.16 mg/kg/week (n=15) and 0.16/0.16 mg/kg/week (n=14) somapacitan, respectively, versus 9.0 (2.3) cm/year for daily GH (n=11). Mean (SD) change from baseline in HV standard deviation score (SDS) was 8.04 (2.52), 6.21 (2.90) and 6.40 (3.04) for somapacitan, respectively, versus 6.58 (3.15) for daily GH. Compared with week 52, mean HV and HV SDS at week 104 were increased in children in the somapacitan 0.04/0.16 mg/kg/week and 0.08/0.16 mg/kg/week treatment groups. Height SDS values improved during the second year of treatment with somapacitan and daily GH, with the greatest change from baseline in the somapacitan 0.16/0.16 mg/kg/week treatment group. The mean (SD) change in height SDS from baseline to week 104 was 1.73 (0.76), 1.87 (0.81) and 2.18 (1.18) for somapacitan, respectively, versus 1.72 (0.65) for daily GH. The observed mean (SD) change in insulin-like growth factor-I (IGF-I) SDS from baseline was similar between the somapacitan 0.08/0.16 and 0.16/0.16 mg/kg/week treatment groups (3.15 [1.17] and 3.21 [1.12], respectively), and slightly higher compared with IGF-I SDS in the 0.04/0.16 mg/kg/week group (2.99 [1.05]) and the daily GH group (3.06 [1.26]). Mean IGF-I SDS values remained below the upper limit (+2) of the normal range for all treatment groups throughout the 104-week trial duration. Somapacitan was well tolerated at all doses investigated, with no new safety or local tolerability issues identified during the 104 weeks of treatment. In conclusion, at week 104, height-based outcomes were similar between somapacitan 0.16/0.16 mg/kg/week and daily GH, with comparable mean change in IGF-I SDS. Furthermore, the key improvements observed in the first year were maintained in the second year of the study.

Pituitary Volume Is a Better Predictor of Growth During Growth Hormone Therapy Than the Growth Hormone Stimulation Test

Abstract Background: Patients with diminished GH secretion are candidates for GH therapy (GHT). The GH stimulation test (GHST) is considered the gold standard for the diagnosis of GH deficiency (GHD), yet the cutoff of 10 ng/mL has not been well validated statistically. Another proposed method to define GHD has been to measure patients’ pituitary volumes (PV), as the size of the gland may correlate with the amount of GH produced. Objective: This study seeks to ascertain whether the GHST or PV is a better predictor of response to GHT, and determine which method can better define true GHD. Patients and Methods: A database at a Pediatric Endocrinology center was queried for patients aged 6-18 yrs who underwent a GHST, MRI, and GHT between 1/2018 - 6/2019. Patients with relevant comorbidities, those with GHST peak ≥ 10.0 ng/mL, and patients that were non-adherent to their GHT were excluded. Clonidine and L-dopa were stimulants for the GHST. MRIs were acquired on a Philips 1.5 or 3.0 T scanner (1mm slices) and PV was calculated using the ellipsoid formula (LxWxH/2). 87 patients met these criteria for analysis. PV was converted to standard deviation scores (SDS) based on age and sex using the largest data set of pituitary volumes available in the literature. To account for sex-related growth rate differences by age, heights at the initial and subsequent time points were also converted to SDS based on age and sex using parameters provided by the National Center of Health Statistics. Response to treatment was defined as change in height SDS over the assessed time interval. The initial height was included as a covariate. R statistical software was utilized to analyze the correlation between response to GHT and GHST peak value, as well as response to GHT and PV. The relationship between GHST peak value and PV SDS was analyzed with a Spearman correlation. Results: The GHST peak was not a significant predictor of growth response to treatment in both the first or second intervals (r= -0.01, p= 0.207 and r= 0.00, p= 0.815 respectively). GHST peak and PV SDS were not correlated (r=0.08, 95% CI: -0.14, 0.28). Lower SDS of PV significantly predicted growth response to therapy in the first 1 to 8.7 months of treatment (n= 87, model r2=0.231, b=-0.05, SE=0.02, P=0.012). This association in the second interval between 7.8 and 17.4 months of treatment was neither as strong as the first interval nor was it statistically significant (n=62, model r2=0.145, b=-0.05, SE=0.03, P=0.127). Within-person growth velocity was greater in the first interval (mean = 0.37, SD = 0.17) than in the second interval (mean = 0.20, SD = 0.16). Conclusion: Our data indicates that PV can be a valuable tool in defining GHD and should be considered a criterion for determining eligibility for GHT. To our knowledge this is the first study to determine that PV is a better predictor of growth response to GHT than the GHST.

Factors influencing growth hormone therapy effect during the prepubertal period in small for gestational age children without catch-up growth

PurposeBecause small for gestational age (SGA) children who fail to experience catch-up growth have an increased risk of short stature in adulthood, growth hormone (GH) treatment is recommended for effective growth. In this study, we evaluated the effect of GH treatment during the prepubertal period and analyzed for correlation between GH treatment response and clinical factors in SGA children.MethodsA retrospective, single-center study was conducted from 2014 to 2020. A total of 34 prepubertal children of short stature up to 4 years of age and born as SGA were enrolled. We recorded clinical data including birth data, age, weight, height, bone age (BA), and insulin-like growth factor 1 (IGF-1) levels.ResultsThe mean gestational age and birth weight were 37.50±2.51 weeks and 2,200.00±546.79 g. At the start of GH treatment, the mean chronological age and BA were 5.54±1.73 years and 4.52±1.85 years, respectively. The height standard deviation score (SDS) (-2.47±0.45) and IGF-1 SDS (0.16±1.57) were calculated. Height velocity was 9.43±1.40 cm during the first GH treatment year and 7.63±1.16 cm during the second year (P<0.05). The treatment growth response was positively correlated with young age (P=0.047) and lower BA (P=0.049) at the start of treatment. In multiple regression analysis, IGF-1 SDS change had a significantly positive association with GH treatment response (P=0.045).ConclusionsGH treatment is effective for short stature SGA children who do not experience catch-up growth. Early initiation of GH treatment improved growth outcomes. As IGF-1 SDS is positively correlated with height SDS, IGF-1 monitoring is important during GH treatment of SGA prepubertal children.

Skeletal disproportion in girls with Turner syndrome and longitudinal change with growth‐promoting therapy

Short stature in Turner syndrome (TS) may be accompanied by skeletal disproportion. This retrospective study investigates growth and disproportion from early childhood to adult height. Data were collected from 59 girls prior to growth hormone (rhGH) treatment and in 30 girls followed up longitudinally. Standard deviation scores (SDS) for height (Ht), sitting height (SH) and sub-ischial leg length (LL) were compared and a disproportion score (SH SDS - LL SDS) calculated. In 59 girls, mean (SD) age 6.6 (2.1) years prior to rhGH treatment, LL SDS of -3.4 (1.1) was significantly lower than SH SDS of -1.2 (0.8) [p<.001]. In girls with Ht SDS < -2.0, disproportion score was > +2.0 in 27 (63%), cf eight (50%) with Ht SDS ≥ -2.0. For the longitudinal analysis, skeletal disproportion prior to rhGH was+2.4 (1.1) and+1.7 (1.0) on rhGH but prior to introduction of oestrogen [p<.001]. Disproportion at adult height was+1.1 (0.8), which was less marked than at the earlier time points [p<.001 for both comparisons]. Change in disproportion SDS over the first two years of rhGH predicted overall change in disproportion from baseline to adult height [R2 51.7%, p<.001]. TS is associated with skeletal disproportion, which is more severe in the shortest girls and present in only half of those with milder degrees of short stature. Growth-promoting therapy may improve disproportion during both the childhood and pubertal phases of growth. Change in disproportion status two years after starting rhGH helps predict disproportion at adult height.

Treatment and long-term follow-up of patients diagnosed with type 1 diabetes mellitus before age 5.

This study aimed to determine the effects of continuous subcutaneous insulin infusion (CSII) treatment on anthropometric measurements, mean HbA1c, and insulin dosage in patients diagnosed under 5 years of age and compare with multiple-dose injection therapy (MDI). Children with type 1 diabetes mellitus, diagnosed <5 years since 2000 and their 19-year follow-up were evaluated retrospectively. Weight, height, body mass index (BMI), blood pressure, and HbA1c values were recorded for each visit. Hundred and five patients (58.1% female, 41.9% male) were included in the study. Sixty-three (60 %) patients were treated by CSII and 42 (40%) by MDI. Mean age at diagnosis was 2.68±1.42 and 3.29±1.30 years respectively. Mean follow-up was 7.42±4.76 and 6.01±4.41 years respectively. For each group, weight standard deviation score (SDS) increased significantly in the first year after the diagnosis (p<0.001), and with the onset of puberty weight SDS decreased significantly (p<0.001). The trend of weight and BMI SDS changes over the years showed similar characteristics in both groups. During follow-up height SDS was similar in both groups except in Tanner stage 5. When puberty was completed, mean height SDS was 0.51±1.03 in CSII and-0.31±0.75 in the MDI group (p: 0.029). Mean HbA1c was significantly lower in the CSII group (7.62±0.82 and 8.17±1.22 respectively). Systolic and diastolic blood pressure change trends during the follow-up were also similar in both groups. CSII treatment had positive effects on metabolic control and height SDS in patients with early-onset diabetes without increasing BMI.

Effectiveness and safety of rhIGF1 therapy in patients with or without Laron syndrome.

ObjectiveThe European Increlex® Growth Forum Database Registry monitors the effectiveness and safety of recombinant human insulin-like growth factor-1 (rhIGF1; mecasermin, Increlex®) therapy in patients with severe primary IGF1 deficiency (SPIGFD). We present data from patients with and without a reported genetic diagnosis of Laron syndrome (LS).DesignOngoing, open-label, observational registry (NCT00903110).MethodsChildren and adolescents receiving rhIGF1 therapy from 10 European countries were enrolled in 2008–2017 (n = 242). The treatment-naïve/prepubertal (NPP) cohort (n = 138) was divided into subgroups based on reported genetic diagnosis of LS (n = 21) or non-LS (n = 117). Multivariate analysis of the NPP-non-LS subgroup was conducted to identify factors predictive of growth response (first-year-height standard deviation score (SDS) gain ≥ 0.3). Assessments included change in height and weight over 5 years and adverse events (AEs).ResultsHeight SDS gain from baseline was greater in the NPP-LS than the NPP-non-LS subgroup after 1 years’ treatment (P < 0.05). In the NPP-non-LS subgroup, 56% were responders; young age at baseline was a positive independent predictive factor (P < 0.001). NPP-non-LS-responders and the NPP-LS subgroup had a similar mean age (6.07 years vs 7.00 years) at baseline and height SDS gain in year 1 (0.64 vs 0.70), although NPP-non-LS-responders were taller (P < 0.001) at baseline. BMI SDS changes did not differ across subgroups. Treatment-emergent AEs were experienced by 65.3% of patients; hypoglycaemia was most common.ConclusionsIn most NPP children with SPIGFD, with or without LS, rhIGF1 therapy promotes linear growth. The safety profile was consistent with previous studies.

Evaluation of the Final Adult Height and Its Determinants in Patients with Growth Hormone Deficiency: A Single-centre Experience from the South-Eastern Region of Turkey

Objective:The aim was to determine the final adult height (FAH) achieved by recombinant human growth hormone (rhGH) treatment, the factors affecting FAH and the success of attaining the genetic potential.Methods:Data of 133 patients treated with rhGH therapy were reviewed retrospectively. Patients were grouped according to diagnosis, either isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD), and by sex, and pubertal status at the beginning of treatment.Results:The mean age of initiation of treatment was 12.3±2.18 years, and the mean duration of rhGH treatment was 3.65±1.5 years. The mean height standard deviation score (SDS) at diagnosis was -3.11±0.75 SD. All patients received a standardized GH dose of 0.033 mg/kg/day. Mean FAH-SDS was -1.8±0.77 and delta height-SDS (the change in height SDS between the beginning and end of treatment) was 1.28±0.94 SD. FAH-SDS was -1.79±0.86 SD in males; -1.82±0.64 in females (p=0.857); -1.94±0.71 at the beginning of treatment in pubertal patients and -1.68±0.81 in prepubertal patients (p=0.056); -1.84±0.89 in patients with IGHD and -0.47±0.2 in patients with MPHD (p˃0.05). In multiple regression analysis, First year delta height-SDS was the most predictive factor for both FAH-SDS and delta height-SDS.Conclusion:The majority of our patients achieved a final height compatible with their genetic potential as well as population standards when treated with rhGH even having started at a relatively late age. First year delta height-SDS was a predictive factor for FAH.

Effectiveness of growth hormone therapy in children with Noonan syndrome.

PurposeRecombinant human growth hormone (rhGH) has been used to improve growth in children with Noonan syndrome (NS). This study aimed to investigate the efficacy of rhGH therapy in Korean children with NS.MethodsSeventeen prepubertal children (10 boys, 7 girls) with NS who received rhGH therapy for at least 3 years between 2008 and 2017 were included. To compare the response, age- and sex-matched children with GH deficiency (GHD; n=31) were included. Height and growth velocity before and during treatment were analyzed.ResultsThe mean age of NS patients was 6.34±2.32 years. After treatment, the height standard deviation score (SDS) increased from -2.93±0.81 to -1.51±1.00 in patients with NS and from -2.45±0.42 to -1.09±0.47 in patients with GHD. There were no significant differences in growth velocity or change in height SDS between patients with NS and GHD. Growth velocity in the first year of treatment was higher in patients with PTPN11 mutations than those without PTPN11 mutations, but the change in height SDS was not significantly different between those 2 groups.ConclusionsrhGH therapy can increase linear growth in prepubertal children with NS. The growth response between patients with NS and patients with GHD was not significantly different. Furthermore, we observed that lower doses of growth hormone have a similar effect on height compared to previous studies in patients with NS. Our study indicates that rhGH treatment is useful for growth promotion.

OR33-01 Liraglutide for Weight Management in Pubertal Adolescents with Obesity: A Randomized Controlled Trial

Background: Pediatric obesity is a chronic disease with rising prevalence and limited treatment options; first-line intervention is lifestyle therapy, which is typically unsuccessful.1 Liraglutide (3.0 mg) as an adjunct to lifestyle therapy has provided weight loss and improved cardiometabolic risk factors in adults.2 Here we report the results of liraglutide 3.0 mg in adolescents with obesity who failed to respond to lifestyle therapy. Methods: A multinational, randomized, double-blind trial (NCT02918279) with a 12-wk run-in of lifestyle therapy, 4-8-wk dose escalation, 52-wk maintenance period and 26-wk follow-up off trial drug. Adolescents aged 12-<18 years with obesity, stable weight and suboptimal response to lifestyle therapy alone were randomized 1:1 to once-daily subcutaneous liraglutide 3.0 mg (or maximum tolerated dose) or placebo (PBO), both as an adjunct to lifestyle therapy. Randomization was stratified by pubertal and glycemic (normal vs prediabetes/type 2 diabetes) status. Primary endpoint was change in BMI standard deviation score (SDS)3 from wk 0 to 56. Results: Of 125 adolescents randomized to liraglutide 3.0 mg and 126 to PBO, 101 and 100 completed treatment at wk 56, respectively; 99 in each arm completed the trial at wk 82. 40.6% were male; mean age 14.5 years; mean BMI 35.6 kg/m2; mean BMI SDS 3.17. Liraglutide 3.0 mg was superior to PBO for change in BMI SDS at wk 56 (estimated treatment difference [ETD] -0.22; 95% CI -0.37, -0.08; p=0.0022). In the liraglutide 3.0 mg vs PBO arm, 43.25% vs 18.73% (p=0.0002) and 26.08% vs 8.11% (p=0.0006) of adolescents had ≥5% and ≥10% reduction in baseline BMI at wk 56, respectively. A significant difference in change in BMI was seen for liraglutide 3.0 mg vs PBO: ETD -4.64%; 95% CI -7.14, -2.14; p=0.0003. A significant reduction in waist circumference with liraglutide 3.0 mg was shown at wk 56 (p=0.0126). Greater weight regain/rebound in BMI SDS at wk 82 was seen for liraglutide 3.0 mg vs PBO after drug discontinuation (ETD 0.15; 95% CI 0.07, 0.23; p=0.0002). There were no significant differences in blood pressure, fasting lipids, fasting plasma glucose or HbA1c at wk 56. No unexpected safety concerns and no severe hypoglycemia were reported. During treatment (0–56 wks), more adolescents in the liraglutide 3.0 mg (64.8%) vs PBO arm (36.5%) reported gastrointestinal adverse events (AEs), and 3 vs 5 adolescents, respectively, reported serious AEs. Mental health questionnaire results were similar in both arms at wk 56. No effect on growth or pubertal development was found. Conclusions: This trial demonstrates clinically meaningful4 weight loss in adolescents with obesity treated with liraglutide 3.0 mg as an adjunct to lifestyle therapy. The safety profile was similar to that observed in adults.