Growth response to growth-hormone administration during the decelerating phase of the pubertal growth spurt in short normal children

In order to investigate the value of growth hormone (GH) treatment during late puberty, we studied the effect of human GH (hGH) administration (0.85 +/- 0.30 IU/kg/week; range: 0.44-1.28) on height velocity (HV) after the peak of the pubertal growth spurt in a group of 10 (4 girls and 6 boys) short normal children (GH peak after pharmacological stimulation: 15.5 +/- 2.3 ng/ml) with growth retardation (height: 2.6 +/- 0.3 SD) and puberty Tanner stage 4. A group of 10 untreated children, observed prior to the study, served as controls. The children were regularly measured during their pubertal growth spurt, and HV (cm/year) was calculated every 6 months. The pretreatment evaluation consisted of 2 consecutive 6-month periods characterized by a decrease in HV of at least 25%. In the group of selected children, hGH administration was then initiated and growth variables were evaluated after 6 and 12 months of therapy. Skeletal maturation was evaluated at the beginning as well as after 6 months and 12 months of hGH therapy. In the controls, HV (mean +/- SD) had decreased from 8.8 +/- 1.8 to 4.9 +/- 1.4 cm/year during the pretreatment period (in girls from 7.9 +/- 1.4 to 4.1 +/- 0.6 cm/year and in boys from 9.6 +/- 1.6 to 5.8 +/- 1.2 cm/year). During the following semester, HV was 3.3 +/- 0.8 cm/year (girls: 3.4 +/- 1.0 and boys: 3.2 +/- 0.2 cm/year).(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlates of objectively measured physical activity in obese children

The aim of this study was to identify potential correlates of objectively measured physical activity in a sample of obese children. A cross-sectional design was used to assess 137 5-9-year-old obese children (mean +/- s.d. age = 8.3 +/- 1.1 years; mean BMI z-score = 2.76 +/- 0.70; 58% girls) from two regional cities in New South Wales, Australia, before commencement in a treatment trial. Correlates examined included age, BMI z, parental BMI, perceived competence, health-related quality of life, daily minutes spent in small screen recreation (SSR), and fundamental motor skill (FMS) proficiency. Physical activity was assessed using accelerometers and values were calculated for % of monitored time spent in moderate- (MPA) and vigorous (VPA)-intensity physical activity and mean counts per minute (CPM). Analyses were conducted separately for boys and girls. Motor skill proficiency was significantly correlated with a number of physical activity variables for boys and girls. For boys, regression analysis revealed object-control proficiency predicted CPM (R(2) = 0.25) and age was a predictor of %MPA (R(2) = 0.56). Age and object-control skill proficiency were salient predictors of %VPA (R(2) = 0.34). For girls, age and daily minutes of SSR were the only significant predictors for CPM (R(2) = 0.13). Age was the sole predictor of %MPA (R(2) = 0.38) and %VPA (R(2) = 0.15). The targeting of FMSs at an early age should be tested in experimental studies as potential strategies to increase physical activity among obese children, particularly for boys. Interventions aimed at reducing sedentary behaviors among obese girls should also be considered.     

Causes of precocious puberty in children referred for evaluation in hospital conditions

INTRODUCTION: Symptoms of precocious puberty (PP) in children always arouse anxiety in their parents. Many children with PP are being hospitalized for the detailed diagnostic work-up. The aim of our study was to analyze the frequency of the variants of PP in children referred to our department. MATERIAL: Retrospective analysis of 119 children (103 girls and 16 boys) referred for hospitalization in the years 2003-2005 due to signs of precocious puberty was performed. RESULTS: Premature thelarche, benign variant of puberty, was diagnosed in 62 (53%) girls, in the mean age of 3.39 (+/- 2.33) years. Their mean height was within 0.7 +/- 1.1 SD. Premature pubarche was diagnosed 30 (25%) children--22 girls and 8 boys in the mean age was 7.24 (+/- 0.81) years. Their mean height was 1.3 +/- 1.0 SD and was significantly higher than normal (p < 0.0001). Premature menarche was diagnosed in 8 (7%) girls in the mean age 4.81 +/-2.26 years. Mean height in this group was normal for age (0.9+/-0.8 SD). PP was diagnosed in 19 (16%) children (11 girls and 8 boys) in the mean age 5.91 +/- 1.63 years. Mean height in this group was 1.6 +/- 0.7 SD, and was significantly higher than the mean for age (p<0.0005). GnRH-dependent type was present in 15 children, diagnosed as idiopathic in 9 girls and 1 boy. In 5 children (4 boys and 1 girl) pathology of central nervous system was found. In 4 children GnRH-independent precocious puberty was diagnosed--in 3 caused by congenital adrenal hyperplasia and in 1 boy by tumour of testis (leydigioma). CONCLUSIONS: Girls with precocious thelarche without growth acceleration present the benign variant of puberty and need clinical follow up only. Boys with clinical signs of precocious puberty should be carefully evaluated to rule out the organic cause.     

Final height in children with idiopathic growth hormone deficiency treated with recombinant human growth hormone: the Belgian experience

BACKGROUND: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. PATIENTS/METHODS: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5-0.7 IU/kg/week (0.17-0.23 mg/kg/week) from the mean +/- SD age of 11.9 +/- 3.1 years during 5.1 +/- 2.1 years. RESULTS: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was -0.7 +/- 1.1 SDS, being 170.4 +/- 7.2 cm in boys and 158.0 +/- 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 +/- 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 +/- 7.0 cm vs. 27.5 +/- 6.6 cm (p < 0.005); girls: 9.6 +/- 7.4 cm vs. 22.2 +/- 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. CONCLUSIONS: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5-0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.     

Sickle cell disease in the People's Republic of Angola. 1. Epidemiology and clinical aspects

In a period of 6 years 819 children affected with drepanocytosis (S. E.) were treated at the children's clinic in Luanda. At the time of diagnosis the age of the 457 boys amounted to 3.4 +/- 2.7 years and that of girls to 4.3 +/- 3.4 years. The age distribution shows that 40.2% of the patients were in their first 2 years of life. Conditions of crisis which affected 70% of the diseased children are typical of this disease. The family anemnesis demonstrated that 13.6% of all brothers and sisters covered were HbSS positive. 34.1% of them died at an age of 3.5 +/- 3.5 years (boys) or 2.4 +/- 2.3 years (girls) respectively. The physical development measured in the body mass shows that it is significantly diminished in comparison with healthy children of the same age. The characteristic symptom of this disease, splenomegaly, existed in 27.8% of the children with a mean age of 2.8 +/- 2.3 years. In one age group of 4.4 +/- 2.6 years it could even be identified in 11.3% of the cases.     

Adult height in congenital hypothyroidism: prognostic factors and the importance of compliance with treatment

OBJECTIVE: To study the growth, puberty and compliance of 66 hypothyroid children and to determine prognostic factors for adult height. PATIENTS: 66 children were included (12 boys, 54 girls). Aetiologies were 43 ectopic glands, 14 thyroid agenesis, 9 dyshormonogenesis. RESULTS: In girls the mean adult height was 164.7 +/- 6.5 cm for a target height (TH) of 162.8 +/- 5.4 cm. In boys the mean adult height was 178.2 +/- 6.4 cm for a TH of 175.7 +/- 4.7 cm. Puberty development was normal. Children who exceeded their TH had an earlier start of treatment versus children who failed to reach their TH: 24.8 +/- 13.5 vs. 42.0 +/- 47.3 days, p = 0.004. Delayed normalisation of TSH is a risk factor for bad compliance. Adequate correlations between treatment variables appeared only in children who exceeded their TH. CONCLUSIONS: TH, day of start of treatment and compliance with treatment are the main prognostic factors for adult height. Early detection of bad compliance is possible.     

Association of pharmacological tests and study of 24-hour growth hormone secretion in the investigation of growth retardation in children: analysis of 257 cases

Growth hormone (GH) secretion can presently be investigated by several methods: pharmacological provocative tests, study of 24-h GH secretion, measurement of somatomedin-C (Sm-C)/insulin-like growth factor (IGF) I, and the growth hormone-releasing hormone (GHRH) test. In order to compare the results obtained, these methods were used in 257 children with growth retardation (169 boys, 88 girls). Their height SD was -2.7 +/- 0.2, chronological age 11 3/12 +/- 1 6/12 years, and bone age 8 4/12 +/- 1 4/12 years. Mean growth velocity was 4.5 +/- 1.5 cm/year. One hundred and thirty-eight boys and 80 girls were prepubertal, and 31 boys and 8 girls were pubertal (B2 G2). All children underwent the study of 24-h GH secretion (n = 257) and pharmacological provocative tests (two tests, n = 213; one test n = 44). Sm-C/IGF I was measured in prepubertal children (n = 131), and a GHRH test was carried out (n = 153). In addition, the mean integrated concentration of growth hormone secretion (IC-GH) was assessed in a control group of 23 children and was found to be 5.4 +/- 1.2 ng/ml/min. The IC-GH in the group as a whole was 2.6 ng/ml/min. The mean maximum peak during pharmacological tests varied considerably according to the test used, ranging from 7.8 ng/ml for the arginine test to 17.1 ng/ml for the glucagon and betaxolol test. The maximum peak and the 24-h IC-GH were not significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)     

The frequency of X-linked mental retardation

600 mentally retarded children, 339 boys and 261 girls aged 5-9 years were examined. Boys to girls ratio (B:G) was found in the total group to be 1.3. Among 257 children with mental retardation of confirmed genetic origin B:G = 1.4, in 129 children with confirmed exogenous defects B:G = 1.04. The significant prevalence of boys over girls was characteristic of children with monogenic forms. The frequency of X-linked mental retardation in the total group, in all mentally retarded boys and in boys with genetic forms was 12.5 +/- 1.3%, 22.1 +/- 2.2% and 28.5 +/- 2.8%, respectively. The frequency of X-linked mental retardation was higher in boys with genetic forms of imbecility.     

Growth, bone maturation and height prediction after three years of therapy with the slow release GnRH-agonist Decapeptyl-Depot in children with central precocious puberty.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin- and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary-gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.     

Growth and pubertal development during and after treatment with a slow-release gonadotropin-releasing hormone agonist in central precocious puberty.

The auxological data of 25 patients (21 girls, 4 boys) with central precocious puberty (CPP), treated for 4 years with a slow-release gonadotropin-releasing hormone agonist [Decapeptyl-controlled release (D-CR) 3.75] every 4 weeks intramuscularly, and of 6 patients (3 girls, 3 boys), treated for 5 years, are presented. After 3 years of D-CR a stabilization of height velocity (HV) at about 4 cm/year was observed. Bone maturation (ratio of change in bone age to change in chronological age; delta BA/delta CA) slowed down to a mean delta BA/delta CA ratio of 0.5 +/- 0.2 (mean +/- SD) measured over 48 months. As a result, predicted adult height (PAH) improved from 156.3 +/- 7.4 to 162.2 +/- 6.8 cm in girls (p less than 0.001) and from 174.4 +/- 18.6 to 184.3 +/- 17.1 cm in boys after 4 years. In the 5th year an ongoing improvement of PAH was observed. 20 additional girls discontinued D-CR for at least 12 months after treatment with D-CR for 2 years or more. In 11 girls menses started after 10.6 +/- 3.1 months; 9 girls had no menarche after 12-16 months. HV increased in the first and second 6 months to a level of about 6.0 cm/year, decreased in the third 6 months after cessation to the level before discontinuing D-CR and decreased further afterwards. Bone maturation (delta BA/delta CA) increased progressively in the first 18 months after discontinuation, with a stabilization at about 1.3. PAH did not change in the first 12 months after discontinuation of D-CR, but showed a decrease afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimating height from arm span measurement in Malawian children

Arm span and standing height were measured in 289 boys and 337 girls aged 6-15 years who were free from physical deformities which can affect stature or arm span. The arm span exceeded height in all age groups of boys and in older girls. At the age of 7, 11 and 12 years girls were significantly taller than the boys and had longer arm span while at the age of 15 years, the trend was opposite. The mean difference between the two anthropometric parameters for boys was 5.45 +/- 4.21 cm (t = 3.556, p < 0.001) and for girls was 4.94 +/- 4.96 cm (t = 3.542, p < 0.001). Correlation coefficient between height and arm span measurements for Malawian boys was 0.983 and for girls was 0.986. Height, arm span and height-arm span difference increased with age of children while height to arm span ratio decreased. The gender difference in height-arm span differences was only significant at the age of 15 years. Multiple regression and cross validation were performed. Height of Malawian children of both sexes can be estimated from equation: Height (cm) = 15.756 + (0.168 x age) + (0.839 x arm span) (SEE = 0.760, R2 = 0.988).     

Age and gender differences in the physical activity patterns of urban schoolchildren in Korea and China

Physical activity in childhood is important as it may establish adult behavior. However, few studies on physical activity in children have been conducted, especially in Asian children.We performed anthropometric measurements of 159 school children in two grades (grade 5: 10-11 years old and grade 8: 13-14 years old) from urban areas of Korea (n=79) and China (n=80). The total daily energy expenditure (TEE) was estimated for 7 consecutive days using an accelerometer.The mean height, weight, and body mass index (BMI) for boys and girls in both countries exceeded the US national reference median (CDC, 2000). Physical activity levels (PALs) were significantly higher in the grade 5 group (10-11 years old) and in girls than in boys for both grades. No significant difference in PALs or daily step-counts (STPs) was observed between 'normal' and 'overweight' subgroups based on BMI, although negative correlations were found between weight, BMI, or %body fat vs. PAL or STP among Korean girls and Chinese boys (r=0.32-0.38, all p<0.05). Daily variation in physical activity was observed in Korean children. In the Koreans (boys and girls, both grades pooled), TEE and STP were significantly lower than the 7-day average on Sundays, whereas for the Chinese population, STP did not clearly differ between the weekends and the week averages.In summary, PALs were higher in the fifth grade boys and girls than in the eighth grade children; interestingly, girls tended to have higher PALs than boys. Daily variation in physical activity was observed in Korea; children were less active on Sundays.     

The capacity to increase GH secretion at puberty reflects the severity of GH deficiency.

This study evaluates the effect of the spontaneous pubertal increase in sex steroids on GH secretion in GH-deficient patients. Fifteen patients (10 boys, 5 girls) with idiopathic isolated GH deficiency diagnosed before puberty (GH peak < 8 micrograms/l after 2 arginine insulin stimulation tests) were reevaluated for their GH secretion using the same test after completion of their hGH therapy and puberty. Their ages at diagnosis and at the last evaluation were 8.2 +/- 0.7 (SE) (range 4.9-14.9) and 17.8 +/- 0.3 years (15-23), respectively. The data at diagnosis and at last evaluation showed that (1) the mean height increased from -4 +/- 0.3 to -2.5 +/- 0.3 SD (p < 0.01), (2) the mean GH peak increased from 4.4 +/- 0.3 (1.6-8) to 7.6 +/- 0.8 micrograms/l (2-13.2, p < 0.01); at the last evaluation, 8/15 patients had GH peak > 8 micrograms/l and (3) the mean plasma insulin-like growth factor I increased from 0.28 +/- 0.05 to 0.42 +/- 0.03 U/ml (n = 6, p < 0.05). The mean increase in the GH peak was 3.2 micrograms/l (-3 to 10.6). It was negatively correlated with the degree of growth retardation at diagnosis (r = -0.74, p < 0.005). We conclude that the increase in the GH peak at puberty in patients with GH deficiency reflects the severity of GH deficiency and that a corrective factor of the cutoff number is necessary for the diagnosis of GH deficiency in puberty.     

Dynamic changes of orexin A and leptin in obese children during body weight reduction

In this study, we describe changes of plasma levels of the hypothalamic neuropeptide orexin A in obese children during the reduction of body weight and its relationship to other biochemical and anthropometrical parameters. We measured orexin A fasting plasma levels by the RIA method in 58 obese children--33 girls and 25 boys; mean age 13.1+/-0.38 years (range 7-18.5) before and after 5 weeks of weight-reduction therapy. Leptin, IGF-1, and IGFBP-3 levels were measured in all the subjects and were compared to orexin A levels and anthropometrical data. Average weight in subjects before weight-reduction was 74.2+/-2.79 kg and after weight-loss 67.4+/-2.60 kg (p<0.0001). Orexin A levels before the therapy were 33.3+/-1.97 pg/ml and after the therapy 51.7+/-3.07 pg/ml (p<0.0001). Levels of orexin A were not significantly different between girls and boys (p=0.7842). We found negative correlation between orexin A and age (r = -0.5395; p<0.0001), body height (r = -0.4751; p=0.0002), body weight (r = -0.4030; p=0.0017) and BMI (r = -0.2607; p=0.0481). No correlation was found between orexin A and IGF-1, IGFBP-3 or leptin. Orexin A plasma levels increased during body weight loss, whereas the reverse was true for leptin levels. These findings support the hypothesis that orexin A may be involved in regulation of nutritional status in children.     

Dietary phytate × calcium/zinc millimolar ratios and zinc nutriture in some Ontario preschool children

Millimolar ratios of phytate/Zn, Ca x phytate/Zn, and Ca x phytate/Zn per 4.2 MJ were calculated from 3-d weighed-food records collected from 62 male (M) (mean age: 58 +/- 7 mo [mean +/- SD]) and 44 female (F) (mean age: 58 +/- 6 mo) preschool children from Southern Ontario. Food-composition values for phytate were based on laboratory analysis and the literature. No gender differences existed for median millimolar ratios of phytate/Zn (median: M, 5.3; F, 5.3), and Ca x phytate/Zn per 4.2 MJ (M, 68.1; F, 59.5), but median intakes of phytate (M, 399; F, 333 mg/d) and median millimolar ratios of Ca x phytate/Zn (median: M, 102.1; F, 72.3; p less than 0.01) were higher for boys than for girls. Of the children, only two (1M, 1F) and 22 (17 M, 5F) had millimolar ratios of phytate/Zn and Ca x phytate/Zn per 4.2 MJ, respectively, that were above critical values. Millimolar ratios of Ca x phytate/Zn (p = 0.06) and Ca x phytate/Zn per 4.2 MJ (p = 0.05) were higher in boys with hair zinc less than 1.07 mumol/g v greater than or equal to 1.07 mumol/g. Analysis of variance showed that height was influenced by an interaction between millimolar ratios of Ca x phytate/Zn per 4.2 MJ and sex (p = 0.0007), when age and midparent height were treated as covariates. Results suggest that dietary Ca x phytate/Zn millimolar ratios, when expressed per 4.2 MJ, influenced the zinc nutriture of these Southern Ontario boys.     

Diagnostic utility of a low-dose gonadotropin-releasing hormone test in the context of puberty disorders

OBJECTIVES: The 10-microg gonadotropin-releasing hormone (GnRH) test assesses pituitary gonadotroph responsiveness, whereas the 100-microg dose assesses maximal secretory capacity. Our aims were to establish normative data for the low-dose test in children and to evaluate the test in diagnosing common pubertal disorders. METHODS: We retrospectively classified 107 children who underwent 10-microg GnRH tests into normal prepubertal (20 boys, 10 girls), normal early pubertal (10 boys, 16 girls), constitutional delay of puberty (CDP, 13 prepubertal boys >12 years), hypogonadotropic hypogonadism (HH, 5 prepubertal boys >12 years), central precocious puberty (CPP, 19 girls) or premature thelarche/variant (13 girls). RESULTS: Peak LH response was higher in prepubertal boys >12 years compared with younger boys (p < 0.01) but showed no further change in early puberty. CDP boys had LH responses similar to prepubertal boys >12 years. HH boys showed an absent LH response which diagnosed HH with 100% sensitivity and 96% specificity. Thelarche girls had LH:FSH peak ratios lower than normal prepubertal (p = 0.001), pubertal (p < 0.05) or CPP (p = 0.001) girls. CONCLUSIONS: We have established normative values for the low-dose GnRH test in children. The test successfully differentiated HH from CDP in boys, and contributed to the differential diagnosis of CPP and premature thelarche in girls.     

Treatment of central precocious puberty with an LHRH agonist (Buserelin): effect on growth and bone maturation after three years of treatment

The LHRH analog Buserelin was used to treat 27 children (21 girls, 6 boys) with central precocious puberty. Nineteen patients had idiopathic precocious puberty and 8 had organic lesions (hamartoma, hydrocephalus or suprasellar arachnoid cyst). All patients received 20 or 30 micrograms/kg/day s.c. of Buserelin, and we obtained plasma E2 less than 20 pg/ml, vaginal maturation index less than 30 in girls or plasma testosterone less than 0.3 ng/ml in boys. The mean growth rate decreased from 9.3 +/- 0.5 to 4.6 +/- 1.3 cm/year after 3 years. The velocity of skeletal maturation decreased so that the final height prediction improved by a mean value of 1.6 SD. As the follow-up increases, this study confirms that LHRHa therapy is effective and potentially improves the final height of children presenting active and severe central precocious puberty.     

Maxillary volume growth in childhood

Nasomaxillary abnormalities in form, position, and development in children are often prominent features of craniosynostosis, and in particular, craniofacial dysostosis. While attempting to quantitatively assess the volumetric maxillary deficiency in these patients, it became apparent that there was no "normal" reference range for maxillary volumes throughout childhood that could be used for comparison. The aim of this study was to generate a model for measuring maxillary volume and subsequent changes throughout childhood. The technique of segmentation was applied to magnetic resonance images obtained in 55 healthy children (30 boys, 25 girls), aged 1 month to 184 months (15.33 years). Maxillary volumes were plotted against age for boys and girls to create a model for normal maxillary growth during the first 15 years of life. Maxillary volumes were larger in boys at all ages. However, the pattern of maxillary growth in boys and girls was similar and could be divided into three periods, each lasting approximately 5 years. During the first 5 years of life, there is a steady increase in maxillary volume, at the end of which the maxilla has reached 53 percent of the volume recorded at 15 years. There is an accelerated rate of growth between 5 and 11 years, which corresponds to the development and eruption of the permanent dentition. Thereafter, until the age of 15 years, the rate of growth of the maxilla plateaus. Maxillary volume in the first 12 months of life is, on average, 29 cm3 in boys and 25 cm3 in girls. By 15 years of age, it has increased to an average of 73.0 cm3 in boys and 59.4 cm3 in girls (an increase by a factor of 2.5 in boys and 2.4 in girls). The difference between the two sexes is statistically significant for the entire series (boys: mean maxillary volume = 56.55 cm3, SD = 24.61; girls: mean maxillary volume = 40.68, SD = 17.69, p = 0.009, one-way analysis of variance).     

Use of the low-dose corticotropin stimulation test for the monitoring of children with asthma treated with inhaled corticosteroids

OBJECTIVE: Subnormal hypothalamic-pituitary-adrenal (HPA) function and rare cases of adrenal crisis have been reported in asthmatic children treated with inhaled corticosteroids. We investigated subnormal HPA activity and followed up affected patients until recovery of normal HPA functions. STUDY DESIGN: 100 children with persistent asthma underwent low-dose corticotropin testing, with the administration of 1 microg of 1-24 ACTH intravenously. Treatments were beclomethasone dipropionate as a metered-dose inhaler, n = 14, budesonide as a dry-powder inhaler, n = 16, fluticasone propionate as a metered-dose inhaler n = 31 or a dry-powder inhaler n = 39. The mean commercially labelled dose was 520 +/- 29 microg/day (mean +/- SEM, range: 160-1,000) and the equipotent dose (which compares the efficiency of these drugs for treating asthma and their responsibility for systemic effects) was 890 +/- 55 microg/day (range: 200-2,000). RESULTS: The mean stimulated cortisol level +/- SEM (and range) of the patient was 482 +/- 12 (148-801), and that of 40 age-matched controls was 580 +/- 12.5 (439-726), (SD = 79). The result was subnormal (more than 2 SD below the mean of the controls) in28 of the 100 patients. One-four stepwise decreases of 10-100% in the daily equipotent doses received by the patients with abnormal low-dose corticotropin testing results led to normal results in subsequent low-dose corticotropin testing in 27 retested patients. The mean time interval between two tests was 5 months (range: 2-6 months) and the mean period required for normalization of the test was 13 months (range: 2-21). Only one case of asthma exacerbation and no adrenal crisis were observed over these periods. CONCLUSIONS: Decreasing daily equipotent doses led to recovery of normal HPA function without asthma exacerbation. Thus, a revision of the doses of inhaled corticosteroids used in asthmatic children with a progressive decrease to the consensus-recommended doses should decrease the systemic effects of inhaled corticosteroids, while minimizing the risk of asthma exacerbation.     

Insulin-like growth factor-1, leptin, body composition, and clinical status interactions in children with cystic fibrosis

BACKGROUND/AIMS: Children with cystic fibrosis (CF) are of increased risk of reduced fat body mass (FBM) and lean body mass (LBM). Serum concentrations of insulin-like growth factor-1 (IGF-1)and leptin could be markers of LBM and/or FBM depletion. To evaluate the relationships between disease activity, body composition, IGF-1 and leptin concentrations in CF children. METHODS: A cross-sectional study with 26 CF children aged 5.0-15.5 years and 33 healthy controls, mean age 9.4 years. Body composition was evaluated by dual-energy X-ray absorptiometry. Fasting blood samples were analyzed for leptin, IGF-1 and IGFBP-3. RESULTS: FBM standard deviation score (SDS; CF boys -0.02 +/- 0.88 vs. 0.78 +/- 0.65, p < 0.01; CF girls -0.37 +/- 1.15 vs. 0.70 +/- 0.97, p < 0.05), leptin concentration (CF boys 2.07 +/- 0.79 vs. 3.07 +/- 1.28 ng/ml, p < 0.05; CF girls 2.71 +/- 0.86 vs. 5.00 +/- 2.95 ng/ml, p < 0.05) and IGF-1SDS (CF boys -1.43 +/- 1.50 vs. -0.32 +/- 0.88, p < 0.05; CF girls -0.66 +/- 1.66 vs. 0.64 +/- 0.57, p < 0.01) were lower in CF children compared to controls. Shwachman score was the strongest predictor of lean body mass (R = 0.63). Leptin levels explain 60% of the variability in FBM. CONCLUSION: Serum concentrations of IGF-1 and leptin are decreased in children with CF and are associated with clinical conditions and body composition.