Initial Height Standard Deviation Score Research Articles

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

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

Evaluation of the growth response to growth hormone therapy in short children with normal growth hormone secretion

Introduction The availability of biosynthetic growth hormone (GH) ensures that children who are deficient can have replacement therapy, but it has also created the opportunity to treat children who are short but do not have a deficiency. The target height of children with short stature who have normal GH secretion, idiopathic short stature (ISS), without treatment, fails to reach their midparental potential. GH therapy for these children has resulted in variable height outcomes. While some children reached or exceeded genetic target height, others did not have a favorable response.Aim The aim of this study was to report the outcome of the children with ISS who had initial height standard deviation score (HtSDS) (Z score) less than −2, with normal stimulated GH levels (>10 μg/l), after treatment with biosynthetic GH for at least 1 year.Patients and methods This retrospective study included 20 children with ISS, with initial HTSDS less than −2, normal stimulated GH levels (>10 μg/l), who were treated with rhGH (0.04 mg/kg/day) for at least 1 year. None had any other systemic or endocrine disorder. All had normal complete blood count, liver, and renal functions.Results Twenty children (15 males and five females) with ISS, aged between 4.3 and 13.8 years (mean=9.88±2.62 years), who had mean peak GH=15.58±6.95 μg, were studied. All received GH treatment (average GH dose was 0.04 mg/kg/day) for a mean duration=2.49±1.61 years. The mean midparental HtSDS (MPHSDS) was −1.23±0.57. Their bone age did not differ significantly compared with their chronological age (the mean difference=−0.13±0.67 years). The mean HSDS before treatment was −2.34±0.41 and after 1 year of GH treatment was −1.83±0.48. This gave a gain of an average of 0.5 SD. At the last visit (after a mean of 2.5 years), the HtSDS −1.57±0.55 SD with a gain of 0.77±0.14 SD versus before treatment. The difference between children HtSDS compared with their MPHSDS was −1.08 SD before treatment that was changed to −0.3 SD at the last visit. The increment in HSDS was positively correlated with the duration of rhGH therapy (r=0.82, P=0.01) and negatively correlated with age at the start of treatment (r=−0.54, P=0.01).Conclusion Growth hormone therapy that benefits short children with normal growth hormone secretion achieves near-normal HSDS and approaches MPHSDS.

Regular intake of cow’s milk with oral immunotherapy improves statures of children with milk allergies

BackgroundChildren who avoid cow’s milk (CM) because of food allergy may show disturbed growth. Calcium insufficiency, in particular, was reported among those who completely avoided dairy products. We retrospectively examined whether oral immunotherapy (OIT) affected the stature of patients who had completely avoided CM owing to their severe CM allergy. MethodsThe CM-OIT group included subjects who had completely avoided milk their entire lives and were administered OIT between 2009 and 2013. The complete milk avoidance (CM-Avoid) group included subjects who were diagnosed with a CM allergy using oral food challenges between 2013 and 2014 who subsequently avoided CM completely. By examining clinical records and questionnaires, we investigated patient height changes over time. We calculated age- and sex-stratified height standard deviation scores (HtSDS) and analyzed changes in HtSDS retrospectively. The observation period was 1–2 years. To exclude pubertal growth spurts, we set the age criteria as less than 11 years in boys and less than 9 years in girls. ResultsWe recruited 29 patients (19 boys) for the CM-OIT group and 20 (9 boys) for the CM-Avoid group. The patients’ median ages at the start of the observation period were 7.5 years (6.1–9.6) for boys and 6.8 years (5.8–7.8) for girls in the CM-OIT group, and 5.4 years (5.0–7.5) for boys and 5.7 years (5.0–7.1) for girls in the CM-Avoid group. The initial HtSDS in the CM-OIT group was −0.31 (median) and increased to −0.22 (median) after OIT (p = 0.016). In contrast, there was no significant change in HtSDS for the CM-Avoid group. ConclusionsPhysical growth of pediatric patients with severe CM allergies, who have avoided CM completely, could be improved by OIT for CM allergy.

Effect of thyroxine on initial catch-up growth in children with hypothyroidism

Background: Hypothyroidism is a common endocrinal cause of growth retardation in children. Following adequate treatment with thyroxine, growth resumes at an accelerated rate which is known as catch-up growth. There are few observational studies from India on the growth parameters following treatment with thyroxine in children with hypothyroidism.Methods: A retrospective study was done in children aged 2-10 years who were newly diagnosed cases of primary hypothyroidism [Total serum Thyroxine (T4) levels <5 µg/dl and serum Thyroid Stimulating Hormone (TSH) levels ˃15 µU/ml] and treated with oral thyroxine to attain euthyroid state. Height measured before starting treatment and at the time of follow up visits was noted, the Height Standard Deviation Scores (HSDS) were calculated. The effect of thyroxine on linear growth was studied.Results: There were 23 children who were diagnosed as having primary hypothyroidism of whom 16(69.6%) were females and 7(30.4%) were males. The mean age of the children studied was 7.3±2.3 years. The mean dose of thyroxine required to maintain euthyroid status was 4.6±2.2 µg/kg/day. Mean duration of follow up was 13.7±2.4 months. The initial HSDS was - 2.31±0.9 which improved to a final value of - 1.7±0.76 (ΔHSDS0.61, p value <0.0001). Mean height velocity was 8.1 cms/year.Conclusions: Following adequate thyroxine replacement therapy catch-up growth occurs and increased growth velocity leads to partial regain of height deficit in the first couple of years of treatment.

Disease Severity and Genotype Affect Physical Growth in Children With Familial Mediterranean Fever.

This study aims to analyze the growth parameters in children with familial Mediterranean fever (FMF) according to disease characteristics including genotype and disease severity by a recently validated tool in relatively more patients. This retrospective study included 126 patients with FMF (70 males, 56 females; mean age 7.3±3.6 years; range, 4.1 to 18 years). MEditerranean FeVer (MEFV) gene analysis was performed with a molecular diagnostics tool by using a next-generation sequencing platform. Disease severity was determined for the first visit by the validated tool in children, international severity scoring system for FMF. Growth parameters including weight and height were investigated after standard deviation (SD) scores were calculated by anthropometric references in Turkish children. Median follow-up duration was 74.7 months (range, 7.5 to 169 months). Ninety-three patients (73.8%) had at least one M694V mutation in MEFV gene. Six patients (4.8%) had severe disease, 58 (46%) had intermediate severity, and 62 (49.2%) had mild disease. Mean height SD score was significantly lower at last visit than before colchicine treatment. Initial and last height and weight SD scores were lower in patients with at least one M694V mutation than those without. However, the difference was statistically significant for only initial height SD score. We also found statistically significant lower initial height, final height, and weight SD scores in patients with intermediate severity-severe disease activity than mild disease. We advise physicians to score disease severity prospectively and pay attention to patients with intermediate severity-severe disease to avoid growth disturbances.

GnRHa/LHRHa are Effective Against Short Stature in Children with Normal Puberty: A Systematic Review and Meta-Analysis

Objectives: We aimed to test the hypothesis that gonadotrophin-releasing hormone agonists (GnRHa) or luteinizing hormone releasing hormone agonists (LHRHa) can increase height gain of short children with normal puberty via a comprehensive meta-analysis on clinical controlled trials. Methods: Literature search was conducted before March 25, 2019. Data extraction and quality assessment were independently completed by two authors. Effect-size estimates are expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI). Results: Five randomized controlled trials and 4 non-randomized controlled trials involving total 340 short children with normal puberty were eligible for analysis. Overall, GnRHa/LHRHa administration resulted in significant gains in height standard deviation score (SDS) (WMD: 0.60 and 0.77 relative to initial height SDS and predicted height SDS; 95% CI: 0.26 to 0.94 and 0.27 to 1.27; p =0.001 and 0.003, respectively) and height (WMD: 4.52 cm and 6.0 cm relative to initial height and predicted adult height; 95% CI: 2.83 to 6.21 and 4.48 to 7.52; p <0.001 and <0.001, respectively), with significant heterogeneity observed for two height SDS comparisons, and effect-size estimates were more obvious when combined with growth hormone. There was a low probability of publication bias for above comparisons, as indicated by Egger's tests. Subgroup and meta-regression analyses revealed that intervention interval, treatment regimen and percentage of boys were potential sources of between-trial heterogeneity. Conclusions: Our meta-analytical findings indicate that GnRHa/LHRHa are effective against short stature in children with normal puberty, especially in combination with growth hormone. Funding Statement: The authors state that they received no financial support for this work. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The authors conducted this meta-analysis of clinical controlled trials in accordance with the standards set forth by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement.

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

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

Is a Combination of a GnRH Agonist and Recombinant Growth Hormone an Effective Treatment to Increase the Final Adult Height of Girls with Precocious or Early Puberty?

The aim of treatment for idiopathic central precocious puberty (ICPP) is to increase final adult stature, for which gonadotropin-releasing hormone agonist (GnRHa) is the gold standard. Early puberty is frequently similar to ICPP, with pubertal onset only slightly advanced. Short stature may result from early pubertal onset. Some studies have suggested that recombinant human growth hormone (rhGH) should be combined with a GnRHa to improve adult height, while others have not. Here, the aim was to compare the efficacy of combined GnRHa and rhGH treatment with GnRHa or rhGH treatment alone, or no therapy, for the improvement of the final height of girls with ICPP or early puberty. Electronic databases of randomized and quasi-randomized controlled trials, in which the efficacy of GnRHa preparations was compared with that of rhGH for the treatment of children with precocious or early puberty, were searched and a meta-analysis conducted. Five studies of early puberty and four studies of ICPP were identified. There were no statistically significant differences between final adult height standard deviation score and initial height standard deviation score in the treatment of early puberty (GnRHa and rhGH versus rhGH alone or no treatment). The overall analysis of the data failed to indicate any benefit of combined therapy, while individual reports suggested that in specific instances combined therapy may be beneficial in preserving or reclaiming growth potential and improving adult height.

Initial catch-up growth in children with hypothyroidism on thyroxine replacement therapy

Background: There is a paucity of observational data from India on initial catch up growth in hypothyroid children started on thyroxine replacement therapy. Methods: We retrospectively studied 44 children and adolescents (32 girls) with a diagnosis of primary hypothyroidism i.e., (thyrotropin > 15 μIU/mL and thyroxine < 55ng/mL). All were started on treatment with oral thyroxine. The dose was adjusted to maintain thyrotropin between 0.5-5 μIU/mL. Height was measured at baseline and at each follow-up visit and height standard deviation scores (HtSDS) were calculated. We studied the therapeutic benefit of thyroxine replacement therapy on growth in the initial couple of years of treatment. Results: Dose of thyroxine required to restore euthyroidism was 4.1±2.5 μg/kg body weight. The dose fell from 9.7±2.4 μg/kg body weight in infants to 3.0±1.5 μg/kg body weight in adolescence (p<0.001). Likewise, the dose per unit body surface area also fell consistently from 207 ± 70.3 μg/m2 in infants to only 89.3±17.9 μg/m2 in adolescents (p<0.001). The initial HtSDS was -2.0±1.5 and this improved by 0.4 to final value of -1.6±1.3 (p < 0.001) after an average follow up of 14.1±2.5 months. The mean catch-up growth velocity, weighted for the duration of follow-up was 7.7 cm/year. Conclusions: The HtSDS deficit because of hypothyroidism is partially regained in the first few years after treatment.

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

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

Efficacy and Safety of Growth Hormone Treatment in Children with Hypochondroplasia: Comparison with an Historical Cohort

Background/Aims: Hypochondroplasia (HCH) is a skeletal dysplasia characterized by disproportionate short stature. The aims of the study are to evaluate efficacy and safety of recombinant human growth hormone (r-hGH) therapy in HCH children, when compared with a historical cohort of untreated HCH children. Methods: Nineteen HCH patients with an initial height standard deviation score (SDS) ≤-2 and a mean age of 9.3 ± 3.1 years were treated with a mean r-hGH dose of 0.053 mg/kg/day over 3 years. Growth charts were derived from the historical cohort (n = 40). Results: Height gain in the treated population was +0.62 ± 0.81 SDS greater than in the general population, and +1.39 ± 0.9 SDS greater than in the historical untreated HCH cohort (mean gain of 7.4 ± 6.6 cm gain). A negative correlation between height gain and age at treatment initiation was reported (p = 0.04). There was no significant difference in response between patients with fibroblast growth factor receptor 3 mutations and those without. No treatment-related serious adverse events were reported. Conclusions: r-hGH treatment is well tolerated and effective in improving growth in HCH patients, particularly when started early. The treatment effect varies greatly and must be evaluated for each patient during treatment to determine the value of continued therapy.

Adult height after growth hormone treatment in Japanese children with idiopathic growth hormone deficiency: analysis from the KIGS Japan database

To identify factors affecting adult height in Japanese patients with idiopathic growth hormone deficiency (GHD), who received growth hormone (GH) treatment during childhood. A retrospective pharmaco-epidemiological study of the effect of GH treatment on adult height standard deviation scores (SDS) was conducted in 374 Japanese patients with idiopathic GHD. During childhood, GH (0.146 +/- 0.023 mg/kg/week) was administered for a mean of 6.4 +/- 2.6 years. The mean adult height was 160.6 +/- 6.3 cm (-1.75 SD; n = 232) in boys and 146.9 +/- 7.3 cm (-2.20 SD; n = 158) in girls after GH therapy. The mean increases in height SDS in boys and girls with severe GHD were 2.13 SD and 1.66 SD, respectively (p < 0.05). These increases were greater than those observed in patients with moderate GHD and mild GHD. The mean adult height of male patients with GHD and gonadotropin deficiency (166.8 cm) was significantly higher (p < 0.05) than that of isolated GHD patients who were either receiving (159.1 cm) or not receiving (160.5 cm) gonadal suppression therapy. The mean adult heights of female patients were 149.6, 146.7, and 146.9 cm, respectively, and these values did not significantly differ. Linear multiple regression analyses of Japanese patients with severe GHD (n = 61) revealed three independent variables that influenced adult height: gonadotropin deficiency, initial height SDS and height velocity during the first year after the initiation of GH therapy.

The long-term follow-up of height in children with epilepsy

Purpose : To assess the height growth of children with epilepsy receiving antiepileptic drugs (AEDs) and the related factors. Methods : The subjects were 148 children diagnosed with epilepsy at Pusan National University Hospital between January 1996 and December 2003, who received AEDs for more than 3 y. We measured height at the initiation of AED medication and at the last visit during AED medication. We analyzed the mean height standard deviation score (SDS) according to several factors, including sex, age at initial medication, seizure type, underlying causes of epilepsy, seizure frequency before AED medication, seizure control, number of AEDs, height SDS before medication, and duration of medication. Results : In the total population, height SDS at initial therapy and last follow-up were -0.06±1.39 versus 0.10±1.12 (P= 0.09). Children with controlled seizures showed a significant increase in height SDS, from -0.12±1.39 to 0.10±1.09 (P= 0.04), and children on medication for less than 6 y showed a significant increase in height SDS, from -0.09±1.54 to 0.21±1.07 (P=0.03). Also, children with negative initial height SDS showed a significant increase in height SDS (P

Adult height in children with short stature and idiopathic delayed puberty after different management

By retrospectively collecting data from nine Italian centres of pediatric endocrinology, we assessed the different management and final outcome of children with short stature and idiopathic delayed puberty. Data were obtained in 77 patients (54 males, 23 females) diagnosed and followed-up in the various centres during the last 15 years. Inclusion criteria were short stature at initial observation and idiopathic delayed puberty diagnosed during follow-up. At first observation, age was 13.8 +/- 1.0 years and height standard deviation score (SDS) was -2.6 +/- 0.6 in males. In females age was 13.1 +/- 0.9 years and height SDS -2.6 +/- 0.4. Local diagnostic and therapeutic protocols included testing for growth-hormone deficiency (six centres) and treatment in case of deficiency or, in the remaining centres, testosterone or no treatment in males, and no treatment in females. At diagnosis, both in males and in females, the auxological features (height SDS, target height SDS and bone age delay) were similar in the patients treated with growth hormone, testosterone or not treated. Overall 32 patients received growth hormone (25 males, 7 females), 33 no treatment (17 males, 16 females) and 12 testosterone. There was no difference in the adult height of males and females in the different treatment groups. In males there were no differences between adult and target height SDSs (growth hormone-treated 0.31 +/- 0.79, untreated 0.10 +/- 0.82, testosterone-treated 0.05 +/- 0.95), between adult and initial height SDSs (growth hormone-treated 1.70 +/- 0.93, untreated 1.55 +/- 0.92, testosterone-treated 1.53 +/- 1.43) and percentage of subjects with adult height above target height. In females, there were no differences between adult and target height SDSs (growth hormone-treated -0.49 +/- 1.13; untreated 0.10 +/- 0.97) and between adult and initial height SDSs (growth hormone-treated 1.76 +/- 0.92; untreated 1.77 +/- 0.98), whereas a significantly higher percentage of patients remained below target height in the growth hormone-treated group (6/7, 85.7% vs 5/11, 31.3%) (P = 0.02). In conclusion, the diagnostic and therapeutic management of the patients with short stature and delayed puberty is different among Italian pediatric endocrinologists. Our data do not support the usefulness of growth-hormone therapy in improving adult height in subjects with short stature and delayed puberty, particularly in the female sex.

Final adult height in children with Prader–Willi syndrome with and without human growth hormone treatment

Short stature is characteristic of children with Prader-Willi syndrome (PWS). While previous studies have demonstrated acceleration of linear height velocity with growth hormone (GH) treatment, the long-term benefit on final adult height (AH) has not been reported. The objective of this study was to compare AH attained in PWS subjects with and without GH treatment. We reviewed the records of 21 children (aged 8.3 +/- 2.7 years) with PWS and confirmed GH deficiency that attained AH after receiving human GH treatment (0.25 +/- 0.06 mg/kg/week) for a period of 7.9 +/- 1.7 years. A group of 39 non-GH-treated adults with matched initial height standard deviation score (SDS) at age 6.8 +/- 1.3 years was used as control. In the GH-treated group the mean initial height and AH-SDS was -1.9 +/- 1.7 and -0.3 +/- 1.2 respectively (P < 0.0001), whereas the mean initial and AH-SDS in the control group was -1.9 +/- 1.3 and -3.1 +/- 1 respectively (P < 0.0001). Scoliosis was seen in 43% and 39% in the GH-treated and control group respectively. Premature adrenarche (PA) was noticed in 57% of GH-treated group. Six subjects in the control group but none of the GH-treated subjects developed type 2 diabetes mellitus. Our data show that administration of GH to children with PWS restores linear growth and final AH without significant adverse effects other than PA. Further studies will be necessary to determine related morbidity and mortality in individuals with PWS that reached final AH with or without GH treatment.

Comparison of growth in primary Fanconi syndrome and proximal renal tubular acidosis

To compare the difference between primary proximal renal tubular acidosis (PRTA) and Fanconi syndrome (FS), and to find out possible risk factors for growth retardation, we studied the long-term growth, clinical, laboratory, and radiological findings associated with the treatment of six children with primary FS and 15 children with PRTA. The ages of the children with FS were much older than those with PRTA at initial diagnosis (7.03+/-3.82 vs. 1.63+/-1.56 years). The height standard deviation score (SDS) at the start of treatment was significantly lower in FS than in PRTA. Catch-up growth was noted in PRTA at the end of follow-up (initial height SDS -2.13+/-1.10 vs. last height SDS -1.33+/-1.43, P=0.023 by paired t-test), whereas apparent linear growth impairment was found in FS in terms of overall growth velocity index (82.70+/-8.37%) and height SDS (initial -3.25+/-0.95 vs. last -3.15+/-0.31, P=0.791). There was also a higher rate of rickets occurrence in FS (3/6 vs. 0/15 in PRTA). Hypophosphatemia during the follow-up period was more frequent for FS than PRTA (69.2+/-26.1% vs. 7.0+/-25.8%, P<0.001), whereas metabolic acidosis (blood HCO(3)<20 mmol/l) was less efficiently corrected in PRTA (49.1+/-20.5% vs. 25.2+/-21.6% in FS, P=0.028). Moreover, the height Delta SDS correlated well with the mean serum P level during the treatment period in these patients (R=0.528, P=0.014 for all children; R=0.917, P=0.01 for FS patients). Our data suggest that metabolic acidosis may not be the sole factor causing growth impairment in FS. Correction of metabolic acidosis may indeed improve growth in PRTA but not in FS. This study indicates that factors other than metabolic acidosis, such as phosphate depletion and delayed diagnosis/treatment, should be considered to be important causes of growth retardation in FS.

Improved growth in young children with severe chronic renal insufficiency who use specified nutritional therapy.

Growth in children with chronic renal failure caused by polyuric, salt-wasting diseases may be hampered if ongoing sodium and water losses are not corrected. Twenty-four children were treated with polyuric chronic renal insufficiency (CRI; creatinine clearance <65 ml/min per 1.73 m(2)) with low-caloric-density, high-volume, sodium-supplemented feedings. Subsequent growth was compared with that of children in two control groups: a national historic population control from the US Renal Data System database (n = 42), and a literature control (n = 12). Members of the three groups were 81 to 96% white, and 58 to 70% were boys. Obstructive uropathy and dysplasia were the cause of CRI in 92% of the treatment group, 75% of the literature control group, and 30% of the population control group. Treatment effect was assessed in a multivariate, retrospective analysis of the height standard deviation score (SDS), simultaneously controlling for the severity of disease by renal replacement therapy, primary cause of CRI, and initial height SDS. The change in SDS (Delta SDS) for height by regression analysis at 1 yr was significantly greater by +1.37 in the treatment group versus the population control (P = 0.017). The 2-yr height Delta SDS by regression analysis adjusted for creatinine clearance was significantly greater by +1.83 in the treatment group versus the literature control (P = 0.003). Nutritional support with sodium and water supplementation can maintain or improve the growth of children with polyuric, salt-wasting CRI. This inexpensive intervention may delay the need for renal replacement therapy, growth hormone treatment, or both in many of these children and may be used in any clinical setting.

Final height after long-term growth hormone treatment in Turner syndrome

Objectives: To study final height after long-term growth hormone (GH) treatment in girls with Turner syndrome (TS). Patients: One hundred fifty three patients with TS, participating in five European trials, were included. They started GH treatment in 1987-1989 at an age of 10 years or older. Mean age at start of treatment ranged between 11.7 and 14.6 years among countries and mean bone age between 9.4 and 11.8 years. Fourteen girls were lost to follow-up, leaving 139 for analysis. Most girls have now attained final height (FH), defined as a linear growth velocity (GV) of 4 mm/yr or less, measured over at least 6 months (group 1, n = 56), or near-FH, defined as a GV of 5 to 9 mm/yr (group 2, n = 22). Sixty-one girls were still growing 10 mm/yr or more. Methods and main results: At the last measurement, mean (SD) height was 150.7 (4.9) cm in group 1 and 148.5 (5.1) cm in group 2. The differences between FH and projected final height based on extrapolation of the initial height-standard deviation score on Turner syndrome reference values, were 2.9 (3.8) and 3.0 (3.3) cm, respectively. The mean gain over the Bayley-Pinneau prediction of FH was 3.3 (3.9) cm in both groups. No significant differences between countries were found. The range of gains over projected height (-4.7 to 12.1 cm) was large, and 25% of gains were 5 cm or more. Gain over initial projection was strongly related to initial growth delay and to growth response during the first 2 years of treatment. A logistic regression model is presented that predicts gain of more than 5 cm with a positive predictive value of 62% and a negative predictive value of 84%. Conclusions: Long-term GH treatment in girls with TS, starting treatment at a relatively advanced age (>10 years) resulted in a modest mean gain in FH of 3 cm, with wide interindividual variation. (J P EDIATR 1995;127:729-35)

Final height and predicted height in boys with untreated constitutional growth delay

We report on 49 boys with constitutional growth delay (CGD) who were initially seen in our clinic at a mean chronological age of 13.3 years (range, 7.3-16.4) and a bone age of 11.1 years (range, 6.0-13.5). All were below the 5th height percentile for chronological age. A positive family history with delayed growth and puberty in one or both parents could be elicited in 75%. All 49 patients were re-examined at a mean age of 22.9 years (range, 20.4-31.2). Measured final height was 171.3 cm (range, 161.2-181.7), which was slightly, but significantly lower than mean target height of 173.0 cm. Final height expressed as standard deviation score (SDS) of a male adult population standard was -1.0 (range, -2.4 to 5), also significantly lower than initial height SDS related to bone age (SDSBA) of -0.5 (range, -1.6 to 2). If related to target height (Tanner), final height was found to correlate positively with the initial bone age deficit and the initial height SDSBA. Observed final height was also compared with the predicted adult height by the methods of Bayley-Pinneau (BP), Tanner-Whitehouse Mark II (TW II) and Roche-Wainer-Thissen. Regression equations between all three prediction methods and final height showed an excellent correlation (P < 0.0001). However, only by the BP method was predicted height very close to and no different from measured final height (paired t-test). Despite this, final height in 16 of 49 patients (32.6%) differed by more than 5.0 cm from BP predicted height.(ABSTRACT TRUNCATED AT 250 WORDS)

A MATHEMATICAL MODEL DESCRIBING CATCH-UP GROWTH IN CELIAC DISEASE

The phenomenon of catch-up growth (CUG) is well known, but still poorly understood. One of the best examples of CUG is the growth pattern after the institution of a glutenfree diet in children with celiac disease (CD). Treatment leads in almost all cases to complete catch-up growth within 2 years. Therefore, the pattern of CUG during adequate treatment of CD may be considered as a model for optimal catch-up growth in children treated with any form of therapy for any growth disturbance. In order to describe this pattern mathematically, we analysed growth data of 17 CD patients who showed growth retardation before therapy and completed CUG before the start of puberty. Two subgroups were formed on the basis of the initial height standard deviation score (HSDSI). Nonlinear regression analysis of the individual growth data expressed as HSDS (corrected for parental height SDS) was carried out using a monomolecular growth function. For each subgroup an equation was found from which the expected HSDS at any given moment(HSDSI) can be calculated:Graphical representation of these equations shows that group 1 undergoes a relatively quick CUG which stabilizes at −0.5 SDS after two years of therapy. Group 2 catches up at a lower rate and stabilizes one year later, but reaches a higher endpoint at +0.4 SDS. These equations provide the clinician with a reference instrument for assessing the efficacy of a growth promoting therapy.