Correspondence on "Sex steroid priming for growth hormone stimulation testing in children and adolescents with short stature: A systematic review".

Duncan et al. reviewed the response to growth hormone stimulation testing after priming in peripubertal children. The concern is that there is little research documenting the response to growth hormone treatment in patients with sex hormone primed growth hormone stimulation testing and those unprimed. The controversy about priming or not can be summarized as follows: if one wants to know if the production of growth hormone during puberty will be adequate in terms of peak growth hormone responses then stimulation with priming should be done.

Increase of jump performance during GH treatment in short children born SGA.

Background: Short children born small for gestational age (SGA) often have low muscle mass. Studies on maximal isometric grip-force (MIGF) observed lower muscle strength in these children. In contrast to MIGF, jumping is an everyday muscle activity for children. Our hypothesis was that GH treatment would cause an increase in jumping strength. So, we aimed to study jumping by mechanography in short SGA children before and during GH treatment. Methods: Monocentric prospective longitudinal study in a tertiary pediatric endocrinology center. We studied 50 prepubertal short children (23 females) born SGA (mean age 7.2 y, height -3.24 SDS) during GH treatment (mean dose 45 µg/kg/d). Main outcome measures were Peak jump force (PJF) and peak jump power (PJP) measured by Leonardo® ground reaction force plate at baseline and after 12 months of GH treatment. Mechanography data were compared to sex, age and height related references (SD-Score). Fitness was estimated as PJP/kg body weight by use of the Esslinger-Fitness-Index (EFI). Results: At start of GH treatment PJP/body weight was low at -1.52 SDS and increased significantly to -0.95 SDS during 12 months of treatment (p<0.001). PJF was low-normal compared to height dependent references and remained unchanged. PJP was normal compared to height dependent references and increased only slightly from -0.34 to -0.19 SDSHT. Conclusions: Jumping performance (EFI) measured by mechanography increased during one year of GH treatment in short children born SGA.

An increase in the developmental tempo affects the secular trend in height in male Austrian conscripts birth cohorts 1951-2002.

OBJECTIVES: Using population-based data on height in Austria from birth cohort 1951 to 2002, we aim to evaluate the secular trends in height and developmental tempo among Austrian young men. METHODS: Data were obtained from the Austrian conscription medical examination. We included 1 205 112 conscripts (18-<20 years) who were born between 1951 and 2002 and 853 645 conscripts (17-<19 years) who were born between 1961 and 2002. Height was measured during the medical examination and was used to evaluate the secular trends of mean height over time. Furthermore, the mean difference in height between conscripts of 17- and 18 years old were compared across birth cohorts. RESULTS: The mean height of conscripts aged 17 years increased by 2.2 cm (p < .0001) in between 1961 and 2002. The mean height of conscripts aged 18 years increased by 4.3 cm (p < .0001) between 1951 and 2002. However, the increase in mean height has slowed down since the 1970 s. The difference in mean height between 17 and 18 years old widened from about 0.1 cm in 1961 to 0.3 cm around 1970 and then steadily narrowed again to 0.1 cm at the end of the study period. CONCLUSIONS: The increasing trend in height slows at the end of the 20th century, the developmental tempo at the population level, however, continued to increase. The difference in mean height between 17 and 18 years old narrowed, which may indicate that young men reached their final height earlier.

Long-acting PEGylated growth hormone in children with idiopathic short stature.

Objective: To evaluate the safety and efficacy of weekly PEGylated-recombinant human growth hormone (PEG-rhGH) in children with idiopathic short stature (ISS) in China. Design and methods: This was a multicenter, phase II study in which all subjects were randomized 1:1:1 to weekly s.c. injections of PEG-rhGH 0.1 (low-dose (LD) group) or 0.2 mg/kg/week (high-dose (HD) group) or control for 52 weeks. The primary end point was change (Δ) in height s.d. score (HT-SDS) from baseline to week 52. Secondary end points were height velocity (HV), bone maturity, insulin-like growth factor-1 (IGF-1) SDS, and IGF-1/insulin-like growth factor-binding protein-3 (IGFBP-3) molar ratio. Results: A total of 360 children with ISS were recruited in the study (n = 120 in each group). At week 52, ΔHT-SDS was 0.56 ± 0.26, 0.98 ± 0.35, and 0.20 ± 0.26 in the LD, HD, and control groups, respectively (within-group P < 0.0001; intergroup P < 0.0001). Statistically significant values of ΔHV, IGF-1, IGF-1/IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P < 0.0001). There were clear dose-dependent responses for all auxological variables. PEG-rhGH was well tolerated throughout the treatment period with treatment-emergent adverse events (TEAEs) reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. The incidence of TEAEs was similar in all treatment groups despite the difference in doses. A total of 27 (8.7%) children experienced drug-related TEAEs. Conclusion: Fifty-two-week treatment with PEG-rhGH 0.1 or 0.2 mg/kg/week achieved significant improvement in HT-SDS and other growth-related variables, including HV, IGF-1 SDS, and IGF-1/IGFBP-3 ratio, in a dose-dependent manner. Both doses were well tolerated with similar safety profiles.

Preliminary results of two novel devices for epiphysiodesis in the reduction of excessive predicted final height in tall stature.

BACKGROUND: In the treatment of tall stature, the reduction of excessive predicted final height can either be achieved by hormonal treatment or surgically by temporary (tED) or permanent (pED) epiphysiodesis. The present study evaluates the preliminary results of two novel devices for tED and pED around the knee to reduce the predicted final height. MATERIALS AND METHODS: A retrospective analysis was performed to evaluate the clinical and radiographic outcome after bilateral epiphysiodesis for the treatment of tall stature. A cohort of 34 patients (16 girls, 18 boys) who underwent either tED or pED between 2015 and 2020 were eligible for analysis based on the electronic patient records and picture archiving and communication system of our orthopaedic teaching hospital. tED was conducted in 11 patients (32%) through bilateral implantation of four RigidTacks™ (Merete, Berlin, Germany) around the knee. Twenty-three patients (68%) received pED, performed with an EpiStop™ trephine (Eberle, Wurmberg, Germany). The mean overall follow-up time was 2.9 years. RESULTS: The mean age at surgery was 12.3 years in girls and 13.2 years in boys. Patients had a mean body height of 175.2 cm in girls and 184.7 cm in boys at surgery. The mean predicted final height was 191.4 cm in girls and 210.4 cm in boys. At the last follow-up, 26 patients (76.5%) had achieved skeletal maturity. The mean height of skeletally mature patients was 187.2 cm in girls and 198.5 cm in boys. A mean reduction of the predicted final height of 5.9 cm in girls and 8.7 cm in boys was achieved, corresponding to a reduction in remaining growth of 46% in girls and 38% in boys. Secondary frontal plane deformities of the knee were detected in 5/11 patients (45.5%) in the tED group and 1/23 treatments (4.3%) in the pED group. CONCLUSIONS: tED and pED have both proven to be efficient at achieving growth inhibition to reduce excessive predicted height. However, tED has been associated with an increased risk of secondary angular deformities of the knee. Furthermore, the risk of implant-related complications and the necessity of a subsequent surgical intervention for implant removal have led our study group to abandon tED when treating tall stature. Long-term results of both procedures are pending.

[What is the best method for estimating final height in patients with precocious puberty?] / ¿Cuál es el mejor método de estimación de talla final en pacientes con pubertad precoz?

Central precocious puberty is the premature activation of the hypothalamic-pituitary-gonadal axis, leading to an early epiphyseal fusion and, in many cases, heights below the genetic target. Therefore, a proper adult stature prediction is essential for the treatment decision. OBJECTIVE: To compare the concordance of final height using height prediction made by two validated methods versus the ge netic target height in girls who consulted due to central precocious puberty. PATIENTS AND METHOD: Retrospective, non-concurrent cohort study including 93 girls with central precocious puberty, who were not treated with LHRH analogs and had reached their final adult height. The data was obtained from the clinical records. To predict height, the Bayley-Pinneau method and the Roche-Wainer- Thissen method were applied, and the results were compared with the genetic target height. The concordance between the estimated final height and the final height obtained was evaluated using the Bland-Altman method. RESULTS: When comparing the final height obtained with that predicted by the Bayley-Pinneau method, there was a mean difference of 1.01 cm, and using the Rocke-Wainer- Thissen method, there was a difference of +0.96 cm. The calculation of the genetic target height showed a difference of +0.05 cm with respect to the final height. CONCLUSION: The prediction of height made by the Bayley-Pinneau and Roche-Wainer-Thissen methods was adequate and, contrary to expectations, it was similar to the calculation of the genetic target height that does not use the age of bone maturation. This also presented better concordance and less dispersion of the results with respect to the final height obtained.

The response to growth hormone treatment in a child with short stature, growth hormone deficiency and autosomal dominant cutis laxa type 3 - case report.

OBJECTIVES: The aetiology of short stature in cutis laxa (CL) syndromes is largely unknown. Herein, we report a case with autosomal dominant CL type 3 (ADCL3) with severe short stature and growth hormone (GH) deficiency. CASE PRESENTATION: A male patient with a genetically confirmed diagnosis of ADCL3 was referred for endocrinological evaluation of short stature at the age of 3.4 years. The examination revealed severe proportional short stature (-4.14 standard deviations (SD) score for height) in a patient born small for gestational age (birth weight 2080 g, -2.46 SD, birth length 41 cm, -4.22 SD). Assessment of GH reserve with two clonidine stimulation tests (0.15 mg/m2) with peak GH values of 8.07 ng/mL and 2.98 ng/mL, respectively, were indicative of GH deficiency. Also, the MRI examination revealed a small size pituitary. Thus, the treatment with somatropin was started. The height deficit significantly improved (from -4.14 SD to -1.48 SD) without side effects during the follow-up of 4.5 years. CONCLUSIONS: With this report, the GH deficiency as a possible cause of short stature in ADCL3 and the response to somatropin administration were reported for the first time in the literature.

The landscape of retesting in childhood-onset idiopathic growth hormone deficiency and its reversibility: a systematic review and meta-analysis.

Objective: Children diagnosed with idiopathic isolated growth hormone deficiency (IGHD) are frequently observed to no longer be GH-deficient at a later stage of growth as a result of 'GHD reversal'. Reevaluation of GH status by stimulation test is currently incorporated into management guidelines at attainment of final height (FH). Over the past three decades, numerous studies have evaluated reversal rates using different methodologies including crucial parameters like GHD aetiology, GH cut-off and retesting time point, with heterogeneous results. We aimed to systematically analyse the reversibility of childhood-onset IGHD dependent on retesting GH cut-offs and retesting time points. Methods: PubMed, Cochrane Library, TRIP database and NHS Evidence were searched for publications investigating the reversibility of IGHD from database initiation to 30 June 2020 following PRISMA recommendations. Study cohorts were pooled according to retesting GH cut-off and time point. Reversal rates were calculated using random-effects models. Results: Of the 29 studies initially identified, 25 provided sufficient detail for IGHD analysis, resulting in 2030 IGHD patient data. Reversal rates decreased significantly as the retesting GH cut-off increased (P = 0.0013). Pooled (95% CI) reversal rates were 80% (59-92%, n = 227), 73% (62-81%, n = 516) and 55% (41-68%, n = 1287) for cohorts using retesting GH cut-offs of 3-4 ng/mL, 5-6 ng/mL and 7.7-10 ng/mL, respectively. Individuals retested at FH (n = 674) showed a pooled reversal rate of 74% (64-82%) compared to 48% (25-71%) when retested before FH (n = 653). Conclusion: Provided evidence supports reevaluation of current IGHD management guidelines. The high reversal rates should instigate consideration of early retesting.

Timing of Puberty, Pubertal Growth, and Adult Height in Short Children Born Small for Gestational Age Treated With Growth Hormone.

CONTEXT: Growth hormone (GH) is used to treat short children born small for gestational age (SGA); however, the effects of treatment on pubertal timing and adult height are rarely studied. OBJECTIVE: To evaluate adult height and peak height velocity in short GH-treated SGA children. METHODS: Prospective longitudinal multicenter study. Participants were short children born SGA treated with GH therapy (n = 102). Adult height was reported in 47 children. A reference cohort of Danish children was used. Main outcome measures were adult height, peak height velocity, age at peak height, and pubertal onset. Pubertal onset was converted to SD score (SDS) using Danish reference data. RESULTS: Gain in height SDS from start of treatment until adult height was significant in both girls (0.94 [0.75; 1.53] SDS, P = .02) and boys (1.57 [1.13; 2.15] SDS, P < .001). No difference in adult height between GH dosage groups was observed. Peak height velocity was lower than a reference cohort for girls (6.5 [5.9; 7.6] cm/year vs 7.9 [7.4; 8.5] cm/year, P < .001) and boys (9.5 [8.4; 10.7] cm/year vs 10.1 [9.7; 10.7] cm/year, P = .002), but no difference in age at peak height velocity was seen. Puberty onset was earlier in SGA boys than a reference cohort (1.06 [-0.03; 1.96] SDS vs 0 SDS, P = .002) but not in girls (0.38 [-0.19; 1.05] SDS vs 0 SDS, P = .18). CONCLUSION: GH treatment improved adult height. Peak height velocity was reduced, but age at peak height velocity did not differ compared with the reference cohort. SGA boys had an earlier pubertal onset compared with the reference cohort.

Prediction of height using ulna length in African-Caribbean children.

Standing height is an essential anthropometric measurement in pediatrics. In children unable to stand upright, measurement of ulna to predict standing height is recommended, but height prediction equations based on the ulna have not been established in children of African ancestry. We hypothesized that such equations would result in lower predicted height compared to using equations derived from non-African children. We measured prospectively standing height and both ulna in 358 African-Caribbean children without bone deformity or muscle disease, referred to two pulmonary function test laboratories. Interobserver variability was low for standing height (n = 54) and ulna measurement (n = 51) (mean biases [95%CI]: -0.02 [-0.99; 0.95] and 0.05 [-0.91; 1.01] cm, respectively), as well as inter-ulna variability (n = 352; mean bias 0.03 95%CI [-0.66; 0.73] cm). We used the mean value of 247 bilateral ulna measurements to calculate prediction equations using a generalized linear model including age, sex, ulna length, and geographic origin group, the latter showing no influence on the model. In the validation population of 107 children, the median difference [inter-quartile range] between standing height and ulna-predicted height was -0.4 [-2.7; 1.0] cm. Of 260 reliable baseline spirometry, there was a strong concordance between bronchial obstruction diagnosis established using standing height or ulna-predicted height (kappa coefficient: 0.85 [0.77; 0.94]) with only 11 (4.3%) children misclassified. The ulna predicted height calculated from African-Caribbean prediction equations resulted in a smaller height than the height calculated using equations derived from non-African children.

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

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

Spatiotemporal clustering and correlates of childhood stunting in Ghana: Analysis of the fixed and nonlinear associative effects of socio-demographic and socio-ecological factors.

Childhood stunting remains a major public health issue in many low- and middle-income countries. In Ghana, the progress made is insufficient to reach the targets set by the 2025 World Health Assembly and the 2030 United Nations Sustainable Development Goals. Although studies have examined the socio-demographic determinants of childhood stunting, there has not been any systematic study to examine the spatial associative effects of the socio-demographic and socio-ecological factors at the district level, where health programmes are implemented and monitored. Bayesian geo-additive semiparametric regression technique was used to analyse five conservative rounds of Demographic and Health Surveys in Ghana, with socio-ecological covariates derived from the Demographic and Health Survey Program Geospatial Covariate datasets to examine the temporal trends in childhood stunting, the extent of geospatial clustering at the district level and their associative relationships with socio-demographic and socio-ecological factors. The findings show that childhood stunting in Ghana is not spatially randomly distributed but clustered. Clustering of high childhood stunting was observed amongst districts in the Upper West, Upper East, Northern, North East, Savannah, and Western North regions, whilst clustering of low childhood stunting was observed in districts in the Greater Accra, Volta, Bono and the Eastern regions. Whist socio-demographic factors were predominantly associated with clustering of districts with high childhood stunting, the socio-ecological factors were mainly associated with clustering of districts with low childhood stunting. The socio-ecological factors identified to have a nonlinear associative effect with childhood stunting were Insecticide Treated Net (ITN) coverage, nightlight composite, travel time to a main settlement and population density. The findings suggest that targeted interventions at the district level are essential to reducing childhood stunting in Ghana.

Body composition in preschool children with short stature: a case-control study.

BACKGROUND: Short stature is defined as height below 2 standard deviations of the population with the same age, gender. This study is aimed to assess the characteristics of body composition in preschool children with short stature. METHODS: Anthropometric measurements and body composition were assessed in 68 preschool children aged 3 to 6 years old with short stature and 68 normal controls matched on age and gender. Height, weight and body composition (total body water, protein, minerals, body fat mass, fat-free mass, soft lean mass, skeletal muscle mass, and bone mineral contents) in the two groups were measured and compared. RESULTS: The total body water, protein, minerals, body fat mass, fat-free mass, soft lean mass, skeletal muscle mass, and bone mineral contents were lower in preschool children with short stature than controls (P < 0.05). Body mass index and fat mass index did not differ between groups. Fat-free mass index was significantly lower in short stature group than controls (t = 2.17, P = 0.03). Linear regression analysis showed that there was a positive correlation between height and fat-free mass index [ß, 1.99 (0.59, 3.39), P = 0.01], a negative correlation between height and body fat percentage [ß, - 0.20 (- 0.38, - 0.01), P = 0.04]. The proportions of fat-free mass in the upper limbs were significantly lower (Right,t = - 2.78,Left t = - 2.76, P < 0.05, respectively) in short stature, although body fat distribution was not. CONCLUSIONS: The fat-free mass such as protein and bone minerals is lower in preschool children with short stature, suggesting the monitoring of fat-free mass for early identification and intervention.

Weight-for-Height, Body Fat, and Development in Children in the East Asia and Pacific Region.

Importance: Weight-for-height z score (WHZ) is a standard indicator of children's nutritional status even though it does not fully reflect body fat. Objective: To examine the combined association of WHZ and body fat with early development in the East Asia and Pacific region. Design, Setting, and Participants: Children from the East Asia-Pacific Early Child Development Scales validation study, with full data available regarding their nutritional status and outcomes, were included in this cross-sectional analysis. In brief, a multilevel stratified random sampling was used to select representative samples from each participating country in the study. WHZ and body fat were independently trichotomized using established references and were combined to form a 9-category exposure variable. Data collection was performed between 2012 and 2014, and the analyses were conducted in June 2021. Main Outcomes and Measures: The binary outcome variable of not being developmentally on track (hereafter referred to as poor development) was defined as a score less than the 25th percentile in the following domains: cognitive, language, socioemotional, motor development, and total development score. Poisson regression models were used to analyze the associations between the combined categories and poor development, adjusted for sociodemographic factors. Results: A total of 6815 children (mean [SD] age, 4.02 [0.8] years; 3434 girls [50.4%]) had full data available and were included in this study. Compared with children with normal weight and normal fat, those with wasting and low body fat had the highest likelihood of total poor development (prevalence ratio, 1.47; 95% CI, 1.28-1.70), followed by those with normal weight but low fat (prevalence ratio, 1.23; 95% CI, 1.11-1.36). Similar associations were found in language, cognitive, and socioemotional development, but not in motor development. Conclusions and Relevance: Poor development was more commonly found in children with low body fat independent of WHZ (wasted or normal weight). Early public health strategies may consider using a combination of WHZ and body fat as an indicator of poor development.

Postural control in adolescent boys and girls before the age of peak height velocity: Effects of task difficulty.

BACKGROUND: Adolescent children experience a critical developmental period marked by rapid biological changes. Research question To describe the longitudinal changes in postural control that occur in adolescent boys and girls before the age of peak height velocity (PHV). METHODS: Here, to address the gap of knowledge, we compared the postural control and activation strategies of the muscles that control the ankle joint in twenty-three boys (age 12.5 ± 0.29) and twenty-one girls (age 10.5 ± 0.32). They performed easy (two legs) and difficult (two legs-eyes closed; one leg) postural balance tasks at 18 and 9 months before PHV and at PHV. We quantified the center of pressure (COP) displacements in the anterior-posterior (AP) and mediolateral (ML) directions and electromyographic (EMG) activity of tibialis anterior (TA) and medial gastrocnemius (MG) muscles. RESULTS: Boys exhibited greater AP and ML COP displacement than girls only for the one leg task (difficult task). Although boys and girls had similar postural control 18 months prior to PHV, girls exhibited lesser COP displacement at 9 months before PHV, which related to greater TA-MG coactivation (R2 = 0.26; p < 0.01). In contrast, postural control was not different between boys and girls with an easy balance task (two legs) performed with eyes open and closed. Rather, we found that all children improved their COP displacement in the ML direction with maturity and both AP and ML COP was significantly lower with eyes open. CONCLUSION: These findings provide novel evidence that postural control is superior in early adolescent girls than boys 9 months prior to PHV, likely associated with an earlier maturation of muscle coordination.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

[The taller the longer? - Body height and life expectancy]. / Je größer, umso länger?

The importance of height for mortality and life expectancy is a matter of controversy. The data on this in different countries vary depending on ethnicity, socio-economic and other factors such as age at the time of the study. Current German data show a positive correlation in younger cohorts in men with hypertension. Vascular factors such as the length of the aorta and its elasticity or stiffness seem to play an important role. A recent Dutch study shows a negative correlation between height and life expectancy in older women. Gender-specific differences in hemodynamics depending on body size or aortic length play a decisive role alongside age at the time of the examination.

GH Responsiveness in Children With Noonan Syndrome Compared to Turner Syndrome.

Background: Despite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital heart defects. TS is an entity with decreased growth hormone (GH) responsiveness. Whether this is found in NS is debated. Methods: Data were retrieved from combined intervention studies including 25 children diagnosed with NS, 40 diagnosed with TS, and 45 control children (all prepubertal). NS-children and TS-girls were rhGH treated after investigation of the GH/IGFI-axis. GH was measured with poly- and monoclonal antibodies; 24hGH-profile pattern analysed by PULSAR. The NS-children were randomly assigned to Norditropin® 33 or 66 µg/kg/day, and TS-girls were consecutively treated with Genotropin® 33 or 66 µg/kg/day. Results: Higher PULSAR-estimates of 24h-profiles were found in both NS-children and TS-girls compared to controls: Polyclonal GHmax24h-profile (Mean ± SD) was higher in both groups (44 ± 23mU/L, p<0.01 in NS; 51 ± 47, p<0.001 in TS; compared to 30 ± 23 mU/L in controls) as was GH-baseline (1.4 ± 0.6 mU/L in NS; 2.4 ± 2.4 mU/L in TS, p<0.01 for both, compared to 1.1 ± 1.2 mU/L in controls). Pre-treatment IGFISDS was 2.2 lower in NS-children (-1.7 ± 1.3) compared to TS-girls (0.6 ± 1.8, p<0.0001). GHmax, IGFI/IGFBP3-ratioSDS, and chronological age at start of GH accounted for 59% of the variance in first-year growth response in NS. Conclusion: Both prepubertal NS-children and TS-girls had a high GH secretion, but low IGFI/IGFBP3 levels only in NS-children. Both groups presented a broad individual response. NS-children showed higher response in IGFI and growth, pointing to higher responsiveness to GH treatment than TS-girls.

GH Resistance Is a Component of Idiopathic Short Stature: Implications for rhGH Therapy.

Idiopathic short stature (ISS) is a term used to describe a selection of short children for whom no precise aetiology has been identified. Molecular investigations have made notable discoveries in children with ISS, thus removing them from this category. However, many, if not the majority of children referred with short stature, are designated ISS. Our interest in defects of GH action, i.e. GH resistance, has led to a study of children with mild GH resistance, who we believe can be mis-categorised as ISS leading to potential inappropriate management. Approval of ISS by the FDA for hGH therapy has resulted in many short children receiving this treatment. The results are extremely variable. It is therefore important to correctly assess and investigate all ISS subjects in order to identify those with mild but unequivocal GH resistance, as in cases of PAPP-A2 deficiency. The correct identification of GH resistance defects will direct therapy towards rhIGF-I rather than rhGH. This example illustrates the importance of recognition of GH resistance among the very large number patients referred with short stature who are labelled as 'ISS'.

The relationship between wasting and stunting in Cambodian children: Secondary analysis of longitudinal data of children below 24 months of age followed up until the age of 59 months.

The interrelationship between wasting and stunting has been poorly investigated. We assessed the association between two indicators of linear growth, height-for-age Z-score (HAZ) change and occurrence of accelerated linear growth, and selected indicators of wasting and wasting reversal in 5,172 Cambodian children aged less than 24 months at enrolment in the 'MyHealth' study. The specific objectives were to evaluate the relationship between temporal changes in wasting and 1) change in HAZ and 2) episodes of accelerated linear growth. At enrolment, the stunting and wasting prevalence were 22.2 (21.0;23.3) % and 9.1 (8.1;10.1) %, respectively, and reached 41.4 (39.3;43.6) %, and 12.4 (11.5;13.3) % respectively, two years later. Between 14-19% of stunted children were also wasted throughout the whole study period. For each centimetre increase in Mid-Upper Arm Circumference (MUAC) from the previous assessment, the HAZ increased by 0.162 (0.150; 0.174) Z-score. We also observed a delayed positive association between the weight for height Z score (WHZ) unit increase and HAZ change of +0.10 to +0.22 units consistent with a positive relationship between linear growth and an increase in WHZ occurring with a lag of approximately three months. A similar positive correlation was observed for the occurrence of an episode of accelerated linear growth. These results show that interventions to prevent and treat wasting can contribute to stunting reduction and call for integrated wasting and stunting programming.