SD In Height Research Articles

Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis

BackgroundSirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients.MethodsThis pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded.ResultsSirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217).ConclusionsSirolimus’s long-term administration is not associated with adverse effects on children’s physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration.Trial registrationPediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

Sex-Specific Long-Term Height and Body Mass Index Trajectories of Children Diagnosed with Attention-Deficit/Hyperactivity Disorder and Treated with Stimulants

To evaluate the sex-specific effects of stimulants in children with attention-deficit/hyperactivity disorder (ADHD) on body mass index (BMI) z and height z trajectories. A retrospective cohort study using the database of Israel Clalit Health Services was performed. Participants included 5- to 18-year-old insured patients with documentation of at least 2 consecutive prescriptions of stimulant drugs for ADHD. Participants were further compared with sex- and age-matched insured control patients without ADHD. A total of 4561 (66% boys) participants with ADHD were included. Of these, 2151 (70% boys) had follow-up data for ≥2years of treatment. A decline of ≥1 SD in height and BMI z score was observed in 10.1% and 13.2% of the cohort, respectively. During ≥2years follow-up, boys had a greater decline in height z score (~0.2 SD) than girls (~0.06 SD). Boys' height z score continued to decline after 1 and≥2years, and girls' height z score declined after 1year, and then stabilized. The trajectory of BMI z score of boys and girls was similar, showing a greater decline after 1year, followed by an incline after ≥2years. Younger age at stimulants initiation, better adherence, longer treatment duration, and lower socioeconomic status were correlated with a greater impact on growth attenuation. The non-ADHD group (n=4561, 66% boys) had baseline height z score and BMI z score similar to those in children with ADHD before treatment initiation. Height z score and BMI z score were greater in children without ADHD compared with children with ADHD following 1year of treatment (P<.001). These findings highlight the importance of growth monitoring accompanied with dietary counseling in children with ADHD treated with stimulants.

Efficacy and safety of replacement treatment in isolated growth hormone deficiency

IntroductionGrowth in patients with isolated growth hormone (GH) deficiency is heterogeneous despite treatment due to the low specificity of diagnostic tests, making it necessary to define efficacy variables. AimsTo evaluate efficacy of hormone replacement therapy in children with isolated GH deficiency. MethodsObservational-ambispective study of patients treated in our department in the last 14 years for isolated GH deficiency. This was defined as a GH level less than 7.4mg/dL in response to 2 stimulation tests in patients with height<2SD and a decreased growth rate. ResultsThe study included a total of 97 patients, of whom 69% were boys. The large majority (89.58%) achieved final height. None of them had side effects. The median dose of GH used was 0.028mg/kg/day (0.03–0.025). There was a gain of 1.17 SD in final height. Around three-quarters (71.13%) of the patients were reassessed in adulthood, of whom 39.4% maintained the deficiency, and 79.31% achieved target range height. Target height, estimated height, and the total pubertal gain were positively correlated with final height, while the bone age/chronological age ratio and the initial insulin-like growth factor-1 showed a negative correlation. ConclusionsA majority of patients reached target size, although only a few of them maintained the deficiency in adulthood. Target size, estimated adult height, and pubertal variables are directly related to adult height, while bone age/chronological age and insulin-like growth factor-1 were inversely related, and these can be used as efficacy variables. No adverse effects were observed in the sample with the doses used for the treatment.

Challenges of Securing Growth Hormone Coverage for Idiopathic Short Stature: Review of the 7-Year Experience at one Institution

Despite U.S. Food & Drug Administration (FDA) approval of growth hormone (GH) for idiopathic short stature (ISS), many providers face challenges obtaining insurance coverage. We reviewed the insurance coverage experience for ISS at our hospital to identify factors predictive of approval or denial. We reviewed charts of patients who underwent GH stimulation testing from July 1, 2009, to April 30, 2017, to identify ISS patients (height <-2.25 SD, subnormal predicted adult height (PAH) and peak GH >10 ng/mL). Eighty-seven patients met ISS criteria, of whom 47 (29 male/18 female) had a GH request submitted to insurance. Mean age, height, and growth velocity were 8.6 ± 2.7 years, 2.83 ± 0.4 SD, and 4.4 ± 1.7 cm/year, respectively. Mean PAH based on bone age was -2.50 ± 0.9 SD, equaling 62 inches for males and 58 inches for females. Most had private managed care insurance (74%). Overall, 17/47 (36%) received treatment approval, 7 immediately and 10 more on appeal. There were no differences in age, height SD, growth rate, insurance type, or PAH between the 17 who were approved and the 30 denied. For 21 patients who were treated, a mean increase in 0.6 SD in height was seen after 1 year. At our institution, GH coverage requests for ISS included very short children mostly ages 6 to 11, with heights well below -2.25 SD and poor PAH. Only 36% were approved even after appeal. This highlights the challenge in our area to secure GH treatment for a FDA-approved indication. Collaboration between pediatric endocrinologists and insurers focusing on height SD and PAH, may improve cost-effective coverage to deserving short children who meet FDA guidelines for ISS treatment. FDA = Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; ISS = idiopathic short stature; PAH = predicted adult height.

Environmental harshness drives spatial heterogeneity in biotic resistance

Ecological communities often exhibit greater resistance to biological invasions when these communities consist of species that are not closely related. The effective size of this resistance, however, varies geographically. Here we investigate the drivers of this heterogeneity in the context of known contributions of native trees to the resistance of forests in the eastern United States of America to plant invasions. Using 42,626 spatially referenced forest community observations, we quantified spatial heterogeneity in relationships between evolutionary relatedness amongst native trees and both invasive plant species richness and cover. We then modelled the variability amongst the 91 ecological sections of our study area in the slopes of these relationships in response to three factors known to affect invasion and evolutionary relationships –environmental harshness (as estimated via tree height), relative tree density and environmental variability. Invasive species richness and cover declined in plots having less evolutionarily related native trees. The degree to which they did, however, varied considerably amongst ecological sections. This variability was explained by an ecological section’s mean maximum tree height and, to a lesser degree, SD in maximum tree height (R2GLMM= 0.47 to 0.63). In general, less evolutionarily related native tree communities better resisted overall plant invasions in less harsh forests and in forests where the degree of harshness was more homogenous. These findings can guide future investigations aimed at identifying the mechanisms by which evolutionary relatedness of native species affects exotic species invasions and the environmental conditions under which these effects are most pronounced.

Growth hormone treatment in children born small for gestational age: One center experience

Objective − The aim of this paper is to present our experience in growth hormone treatment in SGA children. Patients and methods − The study enrolled 35 patients (11.88}2.76 years old) who were followed up during the first two years of treatment with growth hormone (35 mcg/kg/day). Results − During the follow up period our patients showed significant growth catch up. They gained more than 1.5SD in height with a statistical significance of P<0.001. Also, there was a statistically significant improvement in their body mass index (BMI) (P=0.002), but not BMI SD. There was a significant effect of growth hormone treatment on their insulin resistance level. HbA1c also increased significantly, but stayed within the normal range. There were no changes in LDL, HDL and total cholesterol, or triglycerides. Systolic and diastolic blood pressure did not change during the treatment period. The thyroid function test showed no significant changes. Conclusion − Although the follow up period was too short and the number of children too small to demonstrate all the short and long term consequences of growth hormone (GH) treatment, the significant beneficial effect of GH treatment on the height of short SGA children was shown without any serious adverse effects. A significant effort should be made to improve early diagnosis of short stature in SGA children.

The 5th national survey on the physical growth and development of children in the nine cities of China: Anthropometric measurements of Chinese children under 7years in 2015.

To describe the physical growth of healthy children under 7years in China based on the latest national survey and provide more data for revising growth reference and monitoring the impact of social development on children's health and growth. In the cross-sectional survey, 161,774 healthy children under 7years were selected by multistage stratified cluster sampling method in nine cities of China. According to the geographical location, the nine cities were divided into northern, central and southern regions, and each city included urban and suburban areas. Anthropometric measurements were obtained on the spots and other related information was collected with questionnaires. There were slight urban-suburban difference and obvious regional difference in anthropometric measurements in China. Comparison with the 4th NSPGDC in 2005, measurements increased 0.1-1.1kg in weight, 0.5-1.8cm in height in urban areas (except children under 3years) and 0.1-2.5kg in weight, 0.2-3.8cm in height in suburban areas. The urban-suburban difference of those measurements became smaller than 10years ago, but their regional difference persistently exist. Chinese children were 0.36 SD in weight, 0.43 SD in height in urban areas and 0.30 SD in weight, 0.30 SD in height in suburban areas higher than WHO standards. Physical growth of children under 7years old was undergoing a slowly positive secular trend during the latest decade in more economically developed regions of China. Urban-suburban difference of those measurements became smaller, while their regional difference persistently exist. Chinese healthy children under 7years in nine cities was taller and heavier than WHO standards.

Nanostructures and Monolayers of Spheres Reduce Surface Reflections in Hyperiid Amphipods

Transparent zooplankton and nekton are often nearly invisible when viewed under ambient light in the pelagic zone [1-3]. However, in this environment, where the light field is directional (and thus likely to cause reflections), and under the bioluminescent searchlights of potential predators, animals may berevealed by reflections from their body surface [4-7]. We investigated the cuticle surfaces of seven species of hyperiids (Crustacea; Amphipoda) using scanning electron microscopy and found two undocumented features that may reduce reflectance. We found that the legs of Cystisoma spp. (n= 5) are covered with an ordered array of nanoprotuberances 200± 20nm SD in height that function optically as agradient refractive index material [6, 8, 9]. Additionally, we observed that Cystisoma and six other species of hyperiids are covered with a monolayer of homogenous spheres (diameters ranging from 52± 7nm SD on Cystisoma spp. to 320± 15nm SD on Phronima spp.). Optical modeling using effective medium theory and transfer matrix methods demonstrated that both the nanoprotuberances and the monolayers reduce reflectance by as much as 100-fold, depending on the wavelength and angle of the incident light and the thickness of the gradient layer. Even though we only consider surface reflectance and not internal light scattering, our study demonstrates that these nanoprotuberances and spheres can improve crypsis in a featureless habitat where the smallest reflection can render an animal vulnerable to visual predation.

Associations between Body Height and Drinking Status with Diabetes in a Rural, Non-Overweight, Elderly, Japanese Male Population: The Nagasaki Islands Study

Aim: A previous study of ours reported finding a positive association between height and hyperuricemia among non-overweight men (BMI<25kg/m 2 ). Although hyperuricemia is known to be also associated with diabetes, no published study has examined possible associations. Furthermore, while alcohol consumption is also reportedly associated with insulin resistance and risk of diabetes, there have been no reports on associations between height and diabetes which take drinking status into account. Objective: We conducted a cross-sectional study to investigate the associations between height and diabetes in relation to drinking status among 787 non-overweight men aged 60-89 years undergoing a general health check-up. Results: Of the study population consisting of 402 non-drinkers and 385 drinkers, 83 men (46 non-drinkers and 37 drinkers) were diagnosed with diabetes. Independent from classical cardiovascular risk factors, a significant positive association between height and diabetes was established for non-drinkers, whereas drinkers did not show any significant association. The cardiovascular risk factors-adjusted odds ratio (OR) and 95% confidence interval (CI) for diabetes for an increment of 1 SD in height (6.36cm) was 1.44 (CI: 1.03-2.02) for non-drinkers and 1.01 (CI: 0.67-1.53) for drinkers. Conclusions: We were able to establish a significant positive association between height and diabetes for non- overweight, elderly, Japanese, non-drinking men undergoing a health check-up. Since height indicates the influence of childhood social and physical condition childhood social and physical condition may contribute to the development of diabetes later in life.

Assessment of Psychosocial Status among Short-stature Children with and without Growth Hormone Therapy and Their Parents.

To evaluate the psychosocial status of short children with and without growth hormone therapy (GHT) and that of their parents, self-administered questionnaires were collected from patients and parents who regularly visit the outpatient clinics participating in the Child Health and Development Network. Completed questionnaires were received for one hundred and thirteen patients with GHT and 67 patients without GHT. According to the parents, both children with GHT and without GHT have no difficulty in their daily lives (89% vs. 95%) and are positive (56% vs. 65%), respectively. Ninety-eight percent of parents of children with GHT and 83% of parents of children without GHT had expected the current treatment strategy to be effective. Parents of children with GHT are more satisfied with the current therapy than those without GHT (79% vs. 50%), and feel less anxiety about the on-going therapy than (31% vs. 58%, respectively). Children treated with or without equally reported having no difficulty in their daily lives (90% vs. 93%), and being positive in their lives (81% vs. 75%, respectively) despite their short stature. Although less than one third of the patients have been bullied in their classroom (26% with GHT vs. 29% without GHT), younger and shorter children tend to be bullied more often. Short children undergoing GHT and their parents have anxiety regarding their height and expectations of the effect of GHT. It is important for doctors to inform their patients regarding realistic height expectations before starting GHT. Additionally, medical consultation is recommended for patients who remain below -2 SD in height despite GHT.

Assessment of Psychosocial Status among Short-stature Children with and without Growth Hormone Therapy and Their Parents

To evaluate the psychosocial status of short children with and without growth hormone therapy (GHT) and that of their parents, self-administered questionnaires were collected from patients and parents who regularly visit the outpatient clinics participating in the Child Health and Development Network. Completed questionnaires were received for one hundred and thirteen patients with GHT and 67 patients without GHT. According to the parents, both children with GHT and without GHT have no difficulty in their daily lives (89% vs. 95%) and are positive (56% vs. 65%), respectively. Ninety-eight percent of parents of children with GHT and 83% of parents of children without GHT had expected the current treatment strategy to be effective. Parents of children with GHT are more satisfied with the current therapy than those without GHT (79% vs. 50%), and feel less anxiety about the on-going therapy than (31% vs. 58%, respectively). Children treated with or without equally reported having no difficulty in their daily lives (90% vs. 93%), and being positive in their lives (81% vs. 75%, respectively) despite their short stature. Although less than one third of the patients have been bullied in their classroom (26% with GHT vs. 29% without GHT), younger and shorter children tend to be bullied more often. Short children undergoing GHT and their parents have anxiety regarding their height and expectations of the effect of GHT. It is important for doctors to inform their patients regarding realistic height expectations before starting GHT. Additionally, medical consultation is recommended for patients who remain below –2 SD in height despite GHT.

Adult Height and Risk of Coronary Heart Disease: Tehran Lipid and Glucose Study

BackgroundWe assessed the relationship between height and coronary heart disease (CHD) in an urban population of Tehran.Methods4110 participants of the Tehran Lipid and Glucose Study who were 40 years of age or older (1880 men and 2230 women; mean age, 55.1 and 53.0 years, respectively) and free of CHD at baseline were followed for a mean of 9.1 years. We used Cox proportional hazards regression to evaluate the risk of a first CHD event across height tertiles.ResultsFirst CHD events occurred in 239 men and 172 women. The estimated crude HR (95% CI) for CHD events associated with an increment of 1 SD in height was 0.96 (0.28–3.33) in men and 0.84 (0.72–0.97) in women. After adjustment for age, the associations were no longer present. Further adjustment for other confounders had little impact on the results: the HR (95% CI) associated with an increase of 1 SD in height was 1.02 (0.87–1.20) in men and 0.82 (0.66–1.02) in women.ConclusionsAfter adjustment for age, height was not associated with CHD incidence in men or women.

Delayed diagnoses of Turner’s syndrome: Proposed guidelines for change

Objective: To measure the delays in diagnosis of Turner’s syndrome (TS) and to propose strategies for earlier screening and diagnosis. Methods: The medical records of 81 girls with TS were reviewed for age at diagnosis, reason(s) for karyotype analysis, and clinical features including growth failure. Delay in diagnosis was calculated as equal to age at diagnosis for children born with lymphedema and/or 2 or more of the following dysmorphic features: webbed neck, nail dysplasia, high palate, and short fourth metacarpal. For all others, delay in diagnosis was calculated as the difference between the age at which height fell below the 5th percentile and the age at which the diagnosis of TS was made. Results: Lymphedema was the key to diagnosis in 97% of the girls diagnosed with TS in infancy, and short stature was the key to diagnosis for 82% of the girls diagnosed in childhood or adolescence. For girls diagnosed in childhood or adolescence, the delay in diagnosis averaged 7.7 ± 5.4 years. Many had dysmorphic features and/or a history of lymphedema at birth, and diagnosis was made an average of 5.3 years after patients had fallen below the 5th percentile for height. By the time of diagnosis, patients were very short, averaging –2.9 SD in height. Conclusions: The diagnosis of TS is often delayed. We recommend karyotype analysis for all girls with unexplained short stature, delayed puberty, webbed neck, lymphedema, or coarctation of the aorta. Furthermore, karyotype analysis should be strongly considered for those who remain above the 5th percentile for height but have 2 or more features of TS, including high palate, nail dysplasia, short fourth metacarpal, and strabismus. (J Pediatr 2000;137:455-9)

Impact of anatomic closure on somatic growth among small, asymptomatic children with secundum atrial septal defect

We retrospectively identified 92 children aged ≤9 years with isolated secundum atrial septal defect (ASD) with preoperative height or weight z score ≤1.0 (16th percentile), respectively. Children with additional cardiac malformations, chromosomal abnormalities, recognized syndromes, pulmonary hypertension, heart failure, prematurity (<34 weeks’ gestation), or use of cardiac medications were excluded from further analysis. After exclusion, 24 low-weight and 25 low-height children were compared with 48 and 50 age-, gender-, and size-matched normal controls, respectively. Univariate and multivariate analyses were performed separately for height and weight groups for achieving an end point of improvement in height or weight z score by +0.5 after repair. There were no significant preoperative demographic differences. After repair, 50% of low-weight patients improved +0.5 SD in weight within 2.6 years versus 5.6 years for controls (p = 0.02). Similarly, 50% of low-height patients improved +0.5 SD in height within 1.7 years versus 11.6 years for controls (p <0.001). Multivariate analysis also indicated a benefit of repair with relative risks of 2.35 (95% confidence interval 1.20 to 4.62; p = 0.01) and 5.11 (95% confidence interval 2.45 to 10.65; p <0.0001), respectively, for improving height or weight by +0.5 SD in patients with ASD relative to controls. Furthermore, children heavier at repair were less likely to improve in weight (relative risk 0.56 [0.34, 0.92] per 1.0 z [p = 0.02]). Likewise, children older at repair were less likely to improve in height (relative risk 0.77 [0.64, 0.92] per year of age [p = 0.003]). We conclude that undersized children with ASD exhibit improved growth after repair. Poor growth should be considered a relative indication for early ASD repair.

Growth during maintenance hemodialysis: Impact of enhanced nutrition and clearance

Growth of children during maintenance hemodialysis has been reported to be uniformly poor, with a mean annual loss of 0.4 to 0.8 SD in height. We adopted an intensive program of closely monitored energy and protein intake with dialysis urea clearances exceeding conventional recommendations. Twelve prepubertal or early pubertal children (aged 7 months to 14 years) were monitored for an average of 2.2 years (range 4 to 81 months) while receiving maintenance hemodialysis. These children received an average of 90.6% and 155.9% of their recommended energy and protein nutritional intake, respectively. With a prescribed urea clearance of 5 mL/kg/min, we achieved a mean single treatment urea clearance normalized for total body water of 2.00, a urea reduction ratio of 84.7%, and an average time of hemodialysis of 14.8 h/wk, all well beyond current guidelines. Over the course of dialysis treatment, the improvement in height SD score was+0.31 SD/y (+0.32 excluding the 2 children treated with recombinant human growth hormone). Normal growth was achieved without overt obesity and was associated with normal pubertal growth spurt. These findings suggest that the combination of increased dialysis and adequate nutrition can promote normal growth in children treated with long-term hemodialysis. (J Pediatr 1999;134:464-71)

Difference in height associated with a translation start site polymorphism in the vitamin D receptor gene.

The function of 1,25-dihydroxyvitamin D3 in bone development is to regulate the differentiation or proliferation of osteoblastic, osteoclastic, and chondrocytic lineage, affecting bone mineralization and linear bone growth. An A(T/C)G substitution exists in the first of the two putative translation initiation sites in exon 2 of the vitamin D receptor (VDR) gene. We studied the relationship between exon 2 polymorphism and height in 90 healthy Japanese female subjects aged 18-20 y, who had attained final height, in 159 healthy Japanese aged 13 y, and 24 children with constitutional short stature aged 6-10 y less than -1.5 SD in height, mostly with parents of normal height. Exon 2 polymorphism was analyzed by PCR-single strand conformation polymorphism, PCR-direct sequencing, and PCR-restriction fragment length polymorphism. The frequency of the exon 2 polymorphism was genotype CC (ACG/ACG), 0.37; genotype CT (ACG/ATG), 0.51; and genotype TT (ATG/ATG), 0.12 in 249 normal subjects. The mean height of female subjects aged 18-20 y with the genotype CT was 160.3 +/- 4.3 cm (mean +/- SD), whereas that with CC was 4.4 cm lower (p < 0.0001), and that with TT was 2.7 cm lower (p = 0.0302). At age 13 y, this trend was observed, and the mean height SD score of subjects with the genotype CT was taller than homozygotes (CC/CT; p = 0.0363 and CT/TT; p = 0.0208) in 159 subjects. Genotype CT in 24 children with constitutional short stature was less frequent than other genotypes (CC, 0.62; CT, 0.21; TT. 0.17) (chi 2 p value, 0.0171). In conclusion, the exon 2 polymorphism affecting the VDR mRNA and protein is one of the major determinants of adult height at least in female Japanese, which was noted at the age of 13 y examined in both sexes.

The relationship between anthropometric measurements and fractures in women

In a population-based, retrospective study involving post-menopausal women, we investigated the relation between fracture prevalence (risk) and present as well as previous body height and weight. A questionnaire was mailed to 46,353 postmenopausal women aged 50–80 years and there were 29,802 (64.3%) responses. Questions were asked about body height and weight and fractures after the age of 25 and at what year they had occurred. The fractures were grouped according to whether they had occurred within 5 years or 10 years prior to responding to the questionnaire. Main outcome was relative risk (RR) of having sustained a fracture of the hip, radius, or spine within 5 years or within 10 years prior to responding to the questionnaire. RRs for hip and spine fractures were negatively associated with current body mass index, current weight, and weight gain since the age of 25 years. Moreover, the RRs of these fractures were positively associated with current height, height at the age of 25, and height loss since the age of 25 years, with the exception of fracture of the spine and current height. RRs for radius fracture were negatively associated with current body mass index and height loss since the age of 25. Moreover, the RRs for radius fracture were positively associated with current weight and height, weight gain since the age of 25, and weight and height at the age of 25. Height at the age of 25 was a consistent risk factor for all fracture types. The RR of the highest quartile (greatest height) vs. the lowest was 2.5 for having a hip fracture during the past 5 years and 2.3 during the past 10 years, which corresponds to a RR of 1.4 for an increase in 1 SD (5.4 cm) in height at age 25. The RR for spine fracture increased about fivefold in women having sustained ≥3 cm height reduction compared with those who had maintained height. We conclude that tall women have a greater relative risk of experiencing fragility fractures. By using height, women at risk of a later fracture can be selected already at the age of 25 years for later follow-up. Height loss, being strongly associated with fragility fractures, indicates the presence of an already existing osteoporotic condition that should receive evaluation and treatment.

Response to growth hormone in children with chondrodysplasia

Theoretic concerns exist that children with chondrodysplasia will not grow in response to growth hormone (GH) therapy because of an inability of the abnormal growth cartilage to respond. Experience to date, however, suggests that there is an increase in growth velocity, especially during the first year of treatment, which may be beneficial. Growth has increased during the early phases of GH therapy in both patients with achondroplasia and patients with hypochondroplasia. Fourteen patients with achondroplasia in the National Cooperative Growth Study have been treated with an average dose of GH of 0.306 mg/kg per week for an average of 2.1 years and have gained an average of 0.3 SD in height. Twenty patients with hypochondroplasia in the National Cooperative Growth Study have been treated with an average dose of GH of 0.317 mg/kg per week for an average of 2.6 years and have gained an average of 0.7 SD in height. These data suggest that the abnormal growth cartilage in patients with chondrodysplasia responds to GH therapy. The effect on final height cannot be predicted with the currently available data. (J P EDIATR 1996;128:S14-7)

Diagnostic evaluation of short children with height 3 SD or more below the mean.

Most children who are more than 2 SD below the mean in height (less than third percentile) have no definable cause and are considered short-normal, but for children who are 3 SD below the mean (the lowest 0.13%), the prevalence of organic disease is known to be considerably greater. To better define the frequency of different diagnoses in this subgroup and to identify useful clinical findings, we reviewed the charts of all children referred for growth evaluation over a 10-year period who were > or = -3 SD in height, > 2 years old, and prepubertal. Of 60 patients (36 males and 24 females), 22% had constitutional growth delay (CGD), 23% had growth hormone deficiency (GHD), 13% had Turner syndrome, and 22% had various forms of primary growth failure (mostly associated with intrauterine growth retardation). Eight percent had very slow growth over a prolonged period but no definable cause, and 12% did not fall into any of the above groups. For differentiating GHD from CGD, a subnormal height velocity for age during a 4- to 12-month observation period, a low insulin-like growth factor-1/somatomedin C (IGF-1/Sm-C), and low total or free T4, with normal TSH, were all highly predictive of a diagnosis of GHD.

2 FACTORS CONTRIBUTING TO IMPAIRMENT OF GROWTH IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

In 88 ALL pat. (43 ♂ 45 ♀) studied retrospectively, mean chronological age(CA)at diagnosis was 6.0 yrs, mean SDS of height for CA(+0.40SD), height for bone age(BA)(+0.44 SD) and weight (-0.06SD). In 48 pat. now in puberty, mean height for CA has decreased to -0.73SD and mean height for BA is -1.71SD. In 8 pat.final height is -0.68SD when adult height predicted at diagnosis was +0.32SD. Growth impairment was determined by the following: 1)duration of chemotherapy: 5 yrs after diagnosis, mean height SDS for CA was reduced by -0.65 SD and by -1.01 SD respectively in patients treated for 2 and for 5 yrs. 2)Radiation doses: 5 yrs after diagnosis mean height SDS for CA was reduced by -0.34 SD and by -1.14 SD in those receiving 18 Gy and 24 Gy respectively 3) Lack of catch-up growth after therapy : between end of therapy and onset of puberty, height SDS for CA did not change (-0.06 SD). In 16/33 euthyroid pat. evaluated at least 2 yrs after irradiation GH response was blunted (<10 ng/ml) in 2 pharmacological tests. In 11/30 Sm-C was low for CA. No hGH treatment was given. 4)Early puberty in relation to age at diagnosis:in girls diagnosed before or after age 7, M2 started respectively at mean CA of 10.6 yrs (n=16) and 11.4(n=15), accounting for a difference of -0.4 SD in height for CA at puberty. 5) Reduction of pubertal growth spurt : compared to average normal girls, mean pubertal height gain was reduced by 3,8 cm. Pituitary-gonadal function(GnRH-test, n=30) was normal. Conclusion : In ALL pat. growth impairment has several components, differing by time of occurrence and mechanism.