Growth retardation in artistic compared with rhythmic elite female gymnasts

We studied 129 female rhythmic gymnasts (RG) and 142 female artistic gymnasts (AG) who participated in the 1999 Gymnastics World Championship for RG in Osaka, Japan, and the 1999 and 2001 Gymnastics World Championships for AG in Tianjin, China (n = 48), and Ghent, Belgium (n = 94), respectively. RG were taller than average, with a mean height SD score above the 50th percentile, whereas AG were relatively short, with a mean height SD score below the 50th percentile. Both RG and AG followed their respective reported target height SD score, which was above the 50th percentile for the RG and below the 50th percentile for the AG. The RG followed a growth pattern that was higher than their reported target height, whereas AG exhibited a negative growth pattern. RG and AG weighed less than the population mean, with the mean weight for age below the 50th percentile for both groups. RG were taller than AG (t = 17.15; P < 0.001), with a higher reported target height SD score (t = 6.44; P < 0.001), a greater Delta height-reported target height (t = 2.74; P < 0.001), and a lower mean body fat (t = -11.83; P < 0.001) and body mass index (t = -10.73; P < 0.001) than AG. AG started their training at an earlier age than RG (t = 4.13; P < 0.001). Using multiple regression analysis, actual height SD score was independently influenced positively by weight SD score for both RG (b = 0.421; t = 4.317; P < 0.001) and AG (b = 1.404; t = 16.514; P = <0.001), and by reported target height only for RG (b = 0.299; t = 3.139; P = 0.002), and negatively by body mass index only for AG (b = -0.80; t = -9.88; P < 0.001). In conclusion, in elite female AG, a deterioration of growth potential was observed, whereas in RG the genetic predisposition to growth was preserved.     

Growth and pubertal development in elite female rhythmic gymnasts

Optimal growth depends upon both environmental and genetic factors. Among environmental factors that could alter growth and sexual maturation are stress and intensive physical training. The influence of these factors has been documented in a variety of sports, but there is limited information on rhythmic gymnasts, who have entirely different training and performance requirements. The study was conducted during the 13th European Championships in Patras, Greece, and included 255 female rhythmic gymnasts, aged 11-23 yr. The study included measurement of height and weight, assessment of breast and pubic hair development, estimation of body fat and skeletal maturation, and registration of menarcheal age and parental height. Gymnasts were taller than average height for age, with mean height above and mean weight below the 50th percentile. Actual height SD score was positively correlated to weight SD score (P < 0.001), number of competitions (P = 0.01), and body mass index (BMI; P < 0.001). Predicted adult height SD score was positively correlated to weight SD score (P < 0.001) and negatively to body fat (P = 0.004). There was a delay in skeletal maturation of 1.3 yr (P < 0.001). Pubertal development was following bone age rather than chronological age. The mean age of menarche was significantly delayed from that of their mothers and sisters (P = 0.008 and P = 0.05, respectively), was positively correlated to the intensity of training and to the difference between chronological age and bone age (P < 0.001 and P = 0.002, respectively), and was negatively correlated to body fat (P < 0.001). In the elite female rhythmic gymnasts, psychological and somatic efforts have profound effects on growth and sexual development. Despite these aberrations, adult height is not expected to be affected.     

Height velocity and skeletal maturation in elite female rhythmic gymnasts.

Rhythmic gymnasts performing under conditions of high intensity are exposed to particularly high levels of psychological stress and intense physical training, factors that can contribute to the observed delay in skeletal maturation and pubertal development, and alter optimal growth. The study was conducted in the field, during the International, European, and World Rhythmic Sports Gymnastics Championships of the years 1997-2000, and included 104 elite female rhythmic gymnasts, aged 12-23 yr. The study included height and weight measurements, estimation of body fat and skeletal maturation, and registration of parental height. Height, weight, target height, and predicted adult height were expressed as the SD score of the mean height and weight for age, according to Tanner's standards. Gymnasts were taller and thinner than average for age, with height velocity SD score for each age group above the 50th percentile for all age groups (n = 140, mean = 1.9 +/- 2.5). Interestingly, although height velocity in normal girls comes to an end by the age of 15, in our examined rhythmic gymnasts it continues up to the age of 18. There was a delay of skeletal maturation of 1.8 yr (n = 72, r = 0.730, P < 0.001), compensated by an acceleration of height velocity toward the end of puberty. The final adult height was identical to the estimated predicted height at first evaluation, and significantly higher than the genetically determined target height (n = 35, r = 0.58, P < 0.001), denoting that genetic predisposition to final height is not only achieved, but even exceeded. Using multiple regression analysis, target height was the only independent parameter that has been proven to influence positively the height velocity SD score (b = 0.233, t = 2.215, P = 0.029), denoting that genetic predisposition remains the main driving force for the observed efficient catch up growth. In conclusion, the elite rhythmic gymnasts compensate for their loss of pubertal growth spurt by a late acceleration of linear growth. Despite the delay in skeletal maturation, genetic predisposition of growth is not only preserved, but even exceeded.     

Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3 +/- 2.1 yr old at the start of treatment and were treated with either deslorelin (4 microg/kg.d sc) or histrelin (4-10 microg/kg.d) for an average of 6.1 +/- 2.5 yr. Final height averaged 159.8 +/- 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 +/- 9.6 cm) but still significantly less than midparental height (MPH) (163.7 +/- 5.6). Final height averaged 171.1 +/- 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 +/- 14.2 cm) but still significantly less than MPH (178.3 +/- 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height SD score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.     

Final adult height and body mass index after cure of paediatric Cushing's disease

OBJECTIVE: Linear growth data after cure of paediatric Cushing's disease (CD) have been reported infrequently. We evaluated final adult height (FH) and body mass index (BMI) in a cohort of paediatric patients treated successfully for CD. PATIENTS AND METHODS: Fourteen patients (10 male, age range 6.4-16.6 years) fulfilled the diagnostic criteria for CD. All had had transsphenoidal surgery (TSS), combined with pituitary irradiation (RT) (45 Gy in 25 fractions) in six. All were cured (post-TSS cortisol < 50 nmol/l or mean cortisol post-RT < 150 nmol/l). Subjects analysed had bone ages at diagnosis of < 15 'years' (male) and < 13 'years' (female). RESULTS: At diagnosis, height SDS was [mean (range)]-2.5 (-4.2 to -0.8) and body mass index (BMI) SDS +2.7 (0.8-5.1). Following cure, 13 patients had GH deficiency (peak GH < 20 mU/l) and were treated with hGH (+ GnRH analogue in four). Height SDS at FH (n = 10) or latest assessment (n = 4) was -1.3 (-3.9-0.2) and increased compared to diagnosis (P < 0.01). The difference between final or latest height SDS and target height SDS was -1.2 (-3.3-0.5), that is less (P < 0.01) than the difference between the height SDS at diagnosis and target height SDS of -2.4 (-3.9 to -0.5). At final height or latest assessment, BMI SDS was +1.7 (0.4-6.2), being decreased compared to diagnosis (P < 0.05) but greater than the normal population (P < 0.01). CONCLUSION: Catch-up growth was demonstrated in paediatric patients cured from CD, with the majority achieving FH within target height range. Early diagnosis and treatment of GH deficiency is recommended to achieve optimal long-term growth. Excess adiposity remains a potential long-term complication.     

Body composition,IGF-I and IGFBP-3 concentrations as outcome measures in severely GH-deficient (GHD) patients after childhood GH treatment: a comparison with adult onset GHD patients

If GH therapy of children with GH deficiency (GHD) has been adequate, body composition should be comparable to that of patients who have undergone normal childhood development and become hypopituitary thereafter. To assess this, body composition was determined in 92 patients with childhood onset (CO) GHD, aged 18-30 yr, who had been treated to final height with GH for 8.98 +/- 4.30 yr and had stopped treatment 1.57 +/- 1.20 yr previously, but who remained GHD (assessed by a GH stimulation test and IGF-I values). These were compared with 35 age-matched GH-na?ve hypopituitary patients with adult onset (AO) GHD. Lean body mass, fat mass, and total bone mineral content were assessed by dual energy x-ray absorptiometry and corrected for actual height. CO patients were shorter (CO height, -1.18 +/- 1.16 SD score; AO height, -0.38 +/- 1.12 SD score; P < 0.001) and had lower body mass index (CO, 23.19 +/- 5.76 kg/m(2); AO, 28.9 +/- 6.27 kg/m(2); P < 0.001) than the AO group. Although there were gender differences, within genders CO patients had lower lean body mass, fat mass, and bone mineral content (P < 0.001 in all cases) compared with AO patients. Standard deviation scores for IGF-I (CO female, -9.2 +/- 3.1; AO female, -5.2 +/- 2.6; CO male, -6.4 +/- 2.7; AO male, -3.5 +/- 2.3; P < 0.001 within each gender) and IGFBP-3 (CO female, -3.5 +/- 2.5; AO female, -1.7 +/- 1.5; CO male, -2.8 +/- 2.0; AO male, -1.1 +/- 1.6; P < 0.001 within each gender) were significantly lower in the CO group. These results suggest that patients with CO GHD who were treated to final height suffer a significant maturational deficit despite GH replacement during childhood.     

Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma

We analyzed whether childhood craniopharyngioma predisposes to obesity and growth impairment. Height/length, body mass index (BMI), and hypothalamic involvement were evaluated in 90 patients at standardized ages and time points before, after, and at the time of diagnosis. Relevant decreases in height sd score (SDS) started at 10-12 months of age and persisted until diagnosis of childhood craniopharyngioma. Relevant increases in BMI SDS were detectable between 4 and 5 yr of age. Postoperative BMI SDS (yr 1-6) had a weak positive correlation with BMI SDS at the time of diagnosis. In linear regression analysis, hypothalamic tumor involvement (P < 0.001), ponderal index at birth (P = 0.014), and BMI SDS at age 6-7 months (P = 0.029) and at age 5 yr (P < 0.001) had relevant and independent impacts on the development of obesity. Patients with hypothalamic involvement (n = 48) presented lower ponderal index and BMI SDS at birth and higher BMI SDS at the time of diagnosis (P < 0.001) as well as during annual follow-up (P < 0.001) compared with patients without hypothalamic involvement (n = 42). From childhood (3.5-4 yr) to the time of diagnosis, growth rates were reduced for patients with hypothalamic tumor involvement. Patients without hypothalamic involvement presented reduced growth rates in early infancy (age 10-12 months) that persisted until diagnosis. We conclude that reduced growth rates occur quite early in history; BMI SDS increases occur later and are predictive of obesity. Hypothalamic involvement is the major risk factor for obesity in patients with childhood craniopharyngioma.     

Final height in pediatric patients after hyperfractionated total body irradiation and stem cell transplantation

Impaired linear growth has been shown to occur in individuals treated during childhood with single-dose and fractionated total body irradiation (TBI) before stem cell transplantation. Our objective was to describe the final heights attained and patient/treatment factors correlating with final height in a cohort of childhood cancer survivors treated with hyperfractionated TBI (total dose 1375 or 1500 cGy). Thirty individuals (18 men) were included in the study. The mean final height standard deviation score (s.d.s.) was -1.9 +/- 0.2, significantly lower than height s.d.s. at TBI (-0.2 +/- 0.2, P < 0.001). Final height s.d.s. was significantly correlated with age at diagnosis, age at TBI and target height (P = 0.04, P < 0.001, P < 0.001, respectively). Treatment with growth hormone (GH) (n = 7) maintained mean height s.d.s. at -2.0 from the onset of GH therapy until attainment of final height. The mean final sitting height s.d.s. was -2.2 +/- 0.2 (n = 16), significantly shorter than mean final standing height s.d.s. (P < 0.01). In conclusion, treatment with hyperfractionated TBI is associated with a reduction in standing height and an even greater reduction in sitting height. Final height after hyperfractionated TBI was similar to that reported after fractionated TBI.     

Ghrelin concentrations in healthy children and adolescents

OBJECTIVE: In addition to its regulation by GH releasing hormone (GHRH) and somatostatin, release of GH from the pituitary is modulated by a third factor, ghrelin, which is expressed in high concentration in the stomach and is present in the circulation. Ghrelin has also been shown to cause weight gain by increasing food intake and decreasing fat utilization. Ghrelin is a potential candidate hormone to influence nutrient intake and growth. Its role through normal childhood and adolescence has not been fully defined. DESIGN: Cross-sectional study in 121 healthy children (65 male, 56 female) aged 5-18 years, in whom height, weight, body mass index (BMI), pubertal status and measurements of IGF-I, IGFBP-3, IGFBP-1 and leptin were available. METHODS: Serum ghrelin concentrations have been measured in radioimmunoassay (RIA; Phoenix, AZ, USA) that detects active and inactive human ghrelin. Relationships between ghrelin and anthropometric data and growth factors were assessed by correlation and regression analyses. RESULTS: Ghrelin was detected in all samples, with a median concentration of 162 pg/ml, range 60-493 pg/ml. Prepubertal children had higher ghrelin concentrations than those in puberty [218 pg/ml (n = 42) and 157 pg/ml (n = 79), P < 0.001], with significant negative correlations between ghrelin and age (rs = -0.39, P < 0.001) and pubertal stage (rs = -0.42, P < 0.001). The decrease in ghrelin with advancing pubertal stage/age was more marked in boys than girls. In the whole group, ghrelin was negatively correlated to BMI SD (rs = -0.24, P = 0.006) and to weight SD (rs = -0.24, P = 0.008) but not height sds. Ghrelin was also negatively correlated to IGF-I (rs = -0.48, P < 0.001), IGFBP-3 (rs = -0.32, P < 0.001) and leptin (rs = -0.22, P = 0.02) but not IGF-II. It was positively related to IGFBP-1 (rs = +0.46, P < 0.001). In stepwise multiple regression, 30% of the variability in ghrelin through childhood could be accounted for by log IGF-I (24%) and log IGFBP-1 (6%). CONCLUSIONS: The fall in ghrelin over childhood and with puberty does not suggest that it is a direct growth-promoting hormone. However in view of the negative relationship with IGF-I and the positive relationship with IGFBP-1, this fall in ghrelin could facilitate growth acceleration over puberty.     

Frequency of osteopenia in adolescents with early-onset juvenile idiopathic arthritis: a long-term outcome study of one hundred five patients

OBJECTIVE: To determine the frequency of low bone mineral content (BMC) and low bone mineral density (BMD) as long-term complications in adolescents with early-onset juvenile idiopathic arthritis (JIA), and to identify disease variables, patient characteristics, and biochemical bone markers related to low bone mass. METHODS: One hundred five (87%) of 121 adolescent patients with early-onset JIA (ages 13-19 years, 80 girls and 25 boys, mean age at onset of JIA 2.8 years), from a cohort first admitted to the hospital between 1980 and 1985, were assessed after a mean disease duration of 14.2 years. BMC and BMD of the total body, the lumbar spine at L2-L4, and the femoral neck were measured by dual-energy x-ray absorptiometry. Age- and sex-specific reference values from a pooled, healthy reference population were used to calculate Z scores. Low bone mass was defined as a Z score less than -1 SD. RESULTS: Among the 103 adolescent JIA patients who underwent total-body imaging, 41% had low total-body BMC and 34% had low total-body BMD. Compared with adolescent JIA patients who had normal total-body BMC, those with low BMC had lower mean weight (P < 0.001), height (P < 0.001), lean mass (P < 0.001), and remission rates (P = 0.016), had longer duration of active disease (P = 0.013), had higher numbers of active and mobility-restricted joints (P < 0.001 and P = 0.001, respectively), had more disability (P = 0.011), had higher frequencies of joint erosions (P < 0.001), and had higher erythrocyte sedimentation rates (P = 0.033). In multiple linear regression analyses of total-body BMC, 88% of the variance was explained by the duration of active disease, the number of joints with restricted mobility, the bone area, urinary deoxypyridinoline values, age, weight, and height. CONCLUSION: Forty-one percent of the adolescents with early-onset JIA had low bone mass >11 years after disease onset. The development of low total-body BMC was related to the duration of active disease, disease severity, measures of bone resorption, weight, and height.     

The effect of administering gonadotropin-releasing hormone agonist with recombinant-human growth hormone (GH) on the final height of girls with isolated GH deficiency: results from a controlled study

To assess whether delaying puberty may improve final height in GH-deficient children with a poor height prediction at early puberty, we studied 24 girls with isolated GH deficiency until they reached their final height, in a controlled trial. Patients were taking recombinant human GH (r-hGH) substitutive therapy from 2.1 +/- 0.5 yr (0.1 IU/kg.day sc) before entering the study, without showing any improvement in height prediction (149.6 +/- 2.9 vs.150.3 +/- 2.2 cm) on entering puberty. Fourteen girls agreed to add a GnRH agonist (GnRHa) to r-hGH, whereas the remaining 10 decided against it and served as controls. At the start of the study, girls treated with or without GnRHa had similar auxological characteristics (bone age, 10.9 +/- 0.6 vs. 10.7 +/- 1.3 yr; height SD score for chronological age, -1.87 +/- 0.3 vs. -1.82 +/- 0.2), including pubertal development. The GnRHa (long-acting D-Trp-6-GnRH) was given at 60 microg/kg im every 28 days for 1.9 +/- 0.9 yr, then patients continued the r-hGH at the same dosage (3.1 +/- 0.7 yr). At the end of the study, bone age was 16.2 +/- 0.3 yr in GnRHa-treated girls and 16.6 +/- 0.9 yr in controls. Bone maturation was significantly slower during GnRHa (1.4 +/- 0.2 yr), and height SD score for bone age improved (-0.31 +/- 0.3) in comparison with controls (2.6 +/- 0.4 yr and -1.35 +/- 0.3 SD score; P < 0.001 and P < 0.0001, respectively). As a result, girls given the combined therapy reached a final height higher than that of controls (height SD score, -0.39 +/- 0.5 vs. -1.45 +/- 0.2; P < 0.0001) and also higher than their midparental height (-1.1 +/- 0.5; P < 0.0005). Controls reached their midparental height. In conclusion, our results demonstrate that slowing pubertal development with the administration of GnRHa for a limited time may improve final height in GH-deficient girls selected because of a poor height prediction at early puberty.     

Linear growth and final height after treatment for Cushing's disease in childhood

Cushing's disease is associated with growth failure in childhood and adolescence. Growth and final height were analyzed in 10 patients who were cured or in remission after treatment of Cushing's disease. Seven males and 3 females, aged 6.8-17.6 yr (bone age, 3.3-15.4 yr), had transsphenoidal surgery, which was combined with pituitary irradiation (4,500 cGy in 25 fractions) in 5 patients. At presentation, 5 patients were prepubertal (males), and 5 were pubertal (2 males and 3 females). The mean height SD score was -2.15 +/-1.26 (range, -0.21 to -4.32) compared with mean target height SD score of -0.43 +/- 0.58. Height velocity in 6 patients was subnormal (0.9-3.8 cm/yr). After treatment, short-term height velocity, over a mean interval of 0.57 yr, in 8 patients not receiving human GH (hGH) therapy, was variable (range, 0.8-7.6 cm/yr). GH stimulation tests (insulin tolerance test/glucagon) in 9 subjects showed peak GH levels of 0.5-20.9 mU/L. Eight were treated with hGH (14 IU/m2 wk), combined in 2 girls and 1 boy with a GnRH analog. After 1 yr of hGH, the mean height SD score had increased from -2.45 +/- 1.0 at initiation of hGH to -2.07 +/- 1.2 (P = 0.01). GH therapy was continued until final height or latest assessment. The mean final height SD score (n = 6) was - 1.24 +/- 1.38, and at the latest assessment the mean height SD score (n = 4) was - 1.52 +/- 1.33. Combining these 2 groups, the mean height so score was -1.36 +/- 1.29. The difference between final or latest height SD score and target height SD score was 0.93 +/- 1.13, i.e. less (P = 0.005) than the difference between height and target height SD score of 1.72 +/- 1.26 at presentation. In conclusion, catch-up and favorable long-term growth was seen after treatment for Cushing's disease. Posttreatment GH deficiency was frequent, and early hGH replacement may have contributed to the encouraging outcome.     

Determinants of growth during gonadotropin-releasing hormone analog therapy for precocious puberty

In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. The findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure.     

Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: a report from the childhood cancer survivor study

GH deficiency is a common late complication in survivors of pediatric malignancies, particularly those who are treated with radiation (RT) to the hypothalamic-pituitary region. Nonetheless, few reports have assessed final height outcomes in survivors treated with GH. In the present study, we investigated which patient and treatment variables correlate with final height and change in height sd score (SDS) in a large cohort of cancer survivors treated with GH. We previously identified 361 participants in the multicenter Childhood Cancer Survivor Study who were treated with GH. Final height data were available in 183 survivors (120 males). Diagnoses included: central nervous system tumors (n = 90), acute leukemia (n = 64), soft tissue sarcomas (n = 23), and miscellaneous (n = 6). The median age at diagnosis of the primary cancer was 4.6 yr, and the median age at start of GH treatment was 11.3 yr. Mean height SDS at start of GH therapy was -2.03 +/- 0.8, and the mean final height SDS was -1.48 +/- 0.10 (P < 0.001). Final height SDS was positively associated with target height and dose of GH but negatively associated with the presence of concomitant endocrinopathies and dose of spinal RT. Change in height SDS (start of GH-final height) was positively associated with male gender, younger bone age at start of GH, and dose of GH; presence of concomitant endocrinopathies and dose of spinal RT were negatively associated with change in height SDS. Risk factors associated with a final height of -2.0 sd or less included lower doses of GH and exposure to higher doses of spinal RT. Thus, to maximize final height, our findings emphasize the importance of beginning GH therapy at the earliest bone age that is clinically feasible; treating with conventional higher doses of GH; and, when possible, minimizing the dose of spinal RT.     

Growth hormone therapy and growth in children with Noonan's syndrome: results of 3 years' follow-up

Growth data from the first 3 yr of a multicenter study examining the efficacy and safety of recombinant human GH [rhGH; 4 IU (1.3 mg)/m(2).day, sc] in children with Noonan's syndrome (NS) are reported for 23 subjects. Sixteen male and seven female patients (age, 9.3 +/- 2.6 yr at onset of GH therapy, mean +/- SD; range, 4.8-13.7) were each assessed at 1, 2, and 3 yr after starting treatment. Comparisons were made with a group of eight subjects (six males and two females, age, 9.0 +/- 4.1 yr; range, 4.1-14.8) with NS, not treated with rhGH, measured over the same period. All treated subjects underwent annual cardiac assessment. Height SD score increased from -2.7 +/- 0.4 at the start of GH therapy to -1.9 +/- 0.9 3 yr later (P < 0.001, two-tailed t test). This corresponded to an increase in height from 116.1 +/- 13.2 to 137.3 +/- 14.0 cm. Height velocity increased from 4.4 +/- 1.7 cm/yr in the year before treatment to 8.4 +/- 1.7 (P < 0.001), 6.2 +/- 1.7 (P < 0.001), and 5.8 +/- 1.8 (P = 0.01, two-tailed t test compared with baseline) during the first, second, and third years of GH treatment, respectively. Height acceleration was not significant during the second or third years when pubertal subjects were excluded. The comparison group showed an increase in height from 116.0 +/- 19.8 to 131.9 +/- 21.1 cm over the 3 yr (height SD score, -2.7 +/- 0.6 to -2.4 +/- 0.7, P = 0.3). None of the 23 children developed hypertrophic cardiomyopathy during GH treatment. The increase in growth rate in NS resulting from 1 yr of GH therapy seems to be maintained during the second year, although height velocity shows a less significant increase over pretherapy values. Possible abnormal anabolic effects of rhGH on myocardial thickness were not confirmed, and no treated patient developed features of hypertrophic cardiomyopathy.     

Obesity is an independent contributor to functional capacity and inflammation in systemic lupus erythematosus

OBJECTIVE: Obesity induces a proinflammatory state and is a major cause of morbidity in the general population. However, little is known about the effects of obesity in patients with chronic inflammatory illnesses such as systemic lupus erythematosus (SLE). METHODS: One hundred consecutive patients with SLE were studied to determine the relationship between body mass index (BMI) and functional capacity, measures of fatigue, quality of life, and the inflammation markers C-reactive protein (CRP), the erythrocyte sedimentation rate, and interleukin-6 (IL-6). The association between BMI and patient characteristics was determined, and multiple logistic regression models were used to adjust for age, sex, disease activity, and disease-related damage. RESULTS: Thirty-three patients had a normal BMI (< 25 kg/m(2)), 28 were overweight (25-29.9 kg/m(2)), and 39 were obese (> or =30 kg/m(2)). Obese patients had worse functional capacity, more fatigue, and higher concentrations of inflammation markers. The mean +/- SD modified Health Assessment Questionnaire (M-HAQ) score was 0.6 +/- 0.4 in obese patients compared with 0.3 +/- 0.4 and 0.2 +/- 0.3 in overweight patients and those with a normal BMI, respectively (P = 0.001). The mean +/- SD concentrations of CRP in obese patients (10.0 +/- 8.6 mg/liter) were higher than those in patients who were overweight (4.7 +/- 5.4 mg/liter) or had a normal BMI (6.2 +/- 9.9 mg/liter) (P < 0.001). Similarly, concentrations of IL-6 were higher in obese patients (P = 0.003). After adjusting for age, sex, disease activity, and damage indices, the associations between BMI and CRP (P < 0.001), M-HAQ scores (P = 0.005), and IL-6 concentrations (P = 0.01) remained significant. CONCLUSION: Obesity is independently associated with impaired functional capacity and inflammation markers in patients with lupus. Thus, weight loss may improve functional capacity and decrease cardiovascular risk factors.     

Association between physical activity, adiposity, and lipid abnormalities in children with familial hyperlipidemia.

BACKGROUND: The benefits of physical activity in children have been studied extensively; however, its role in children with familial hyperlipidemia (FH) is unknown. OBJECTIVE: To determine associations between physical activity, adiposity, and lipid profiles in children with FH. DESIGN: A physical activity questionnaire was completed by 147 children with FH. Correlations between activity levels, body mass index (BMI), and fasting lipid profiles were determined. RESULTS: The mean age of patients was 12.5+/-3.2 years with a mean total cholesterol of 6.17 mmol/l (238 mg/dl), low-density lipoprotein-cholesterol of 4.43 (171), high-density lipoprotein-cholesterol of 1.08 (42), and triglyceride levels of 1.51 (134). Patients had greater weight for height indices than normal, with a mean BMI z score of +0.90+/-1.30 SD (P<0.001 versus normal), and with 21% of the participants being more than 2 SD above normal. Higher BMI z scores significantly correlated with higher triglyceride levels (r=0.33; P<0.0001) and greater time spent in sedentary pursuits (r=0.24; P=0.004), in particular watching television (r=0.26; P=0.003). The increased time that other family members spent in physical activity significantly correlated with a lower BMI z score (r=-0.21; P=0.01) of the patient and greater time spent in physical activity (r=0.24; P=0.003). There was no association between patients' physical activity levels and lipid profile or BMI. CONCLUSION: Similar to the general population, children with FH are also at risk of becoming overweight. Increased adiposity significantly correlated with the greater sedentary activities of the patient, lower physical activities of the family, and higher triglyceride levels. Physical activity levels of the patient correlated with family activity levels.     

Elderly people with hypothalamic-pituitary disease and growth hormone deficiency: lipid profiles, body composition and quality of life compared with control subjects

OBJECTIVE: In healthy adults the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) declines with ageing and body composition alters, particularly with an increase in total body fat. In elderly people, hypothalamic-pituitary disease can cause GH deficiency (GHD), compared with age matched controls. This study aimed to clarify whether GHD in the elderly is associated with differences in body composition, circulating lipid levels and quality of life (QOL) compared with control subjects. SUBJECTS: Twenty-seven elderly patients (14 males, mean age 71 years, range 65-83) with hypothalamic-pituitary disorders (23 pituitary tumours) and GHD (mean (SD) peak stimulated GH response 1.6 mIU/l (1.03) range 0.6-5) were studied. Twenty-five patients had been treated surgically (six cranial surgery, 19 transsphenoidal) and eight patients had received external cranial irradiation. Twenty-seven control subjects (14 males, mean age 72 years, range 65-86) were also studied. METHODS: Weight, body mass index (BMI), total fat mass (FM, bioelectrical impedance), waist to hip ratio (WHR), serum IGF-1, fasting blood glucose and lipid profile were measured. QOL was assessed in both groups using five interviewer administered self-rating questionnaires: The Nottingham Health Profile, Short-Form 36, Hospital Anxiety and Depression Scale, Mental Fatigue Questionnaire and Life Fulfilment Scale. The GHD group also completed the Disease Impact Scale. RESULTS: The data (mean (SD)) from males and females were analyzed separately. The male patients had a higher BMI than controls, 28.9(4.5) vs. 25.2(2.3) kg/m2 (P = 0.01) but the BMI in the female patients and controls was similar. In the female patients compared with the controls, FM was higher 39. 4(6) vs. 33.1(8.3) % (P = 0.02), WHR was also higher 0.9(0.08) vs. 0. 83(0.09) (P = 0.03) and serum IGF-1 levels were lower 10.8(6.4) vs. 18.2(6.5) nmol/l (P = 0.01). However, in the male patients, FM, WHR and IGF-1 levels were similar to the controls. Fasting blood glucose was similar in both male and female patients and the controls. Two female patients and one male control subject were taking lipid-lowering agents and were therefore excluded from the analysis of lipid profiles. Total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol and total cholesterol/HDL cholesterol ratio were not significantly different for both male and female patients compared with the controls. The 27 patients with GHD reported significantly less energy (P < 0.05), mobility (P < 0.05) and personal life fulfillment (P < 0.01) than the 27 controls. There were significantly more problems with emotional reaction (P < 0.01), social isolation (P < 0.05) and mental fatigue (P < 0.05). Additionally the GHD group reported more impairment in areas of social functioning (P < 0.05), general health (P < 0.05) and mental health (P < 0.05). The GHD group reported a modest degree of disease impact (mean score of 14.1). There were no significant differences in the domains of material life fulfillment, pain, sleep, physical functioning, vitality, anxiety, depression, self-esteem or role physical functioning compared with the controls. CONCLUSION: Compared with control subjects, the elderly female patients with hypothalamic-pituitary disease and GHD had a significantly higher total fat mass, with the WHR indicating a more central fat distribution and lower female serum IGF-1 levels. In contrast, elderly male patients had similar total fat mass, WHR and IGF-1 levels compared to the controls. There were no significant differences in the lipid profiles between male or female patients compared to controls. However, many of the male patients were receiving androgen replacement which might have influenced these results. Low HDL cholesterol concentrations are probably a better predictor of future cardiovascular disease than raised LDL cholesterol levels in the elderly population and these were similar in patients and controls for both     

Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature: the influence of pituitary magnetic resonance imaging findings

We analyzed the final height of 146 short children with either nonacquired GH deficiency or idiopathic short stature. Our purpose was 1) to assess growth according to the pituitary magnetic resonance imaging findings in the 63 GH-treated children with GH deficiency and 2) to compare the growth of the GH-deficient patients with normal magnetic resonance imaging (n = 48) to that of 32 treated and 51 untreated children with idiopathic short stature (GH peak to provocative tests >10 microg/liter). The mean GH dose was 0.44 IU/kg.wk (0.15 mg/kg.wk), given for a mean duration of 4.6 yr. Among the GH-deficient children, 15 had hypothalamic-pituitary abnormalities (stalk agenesis), all with total GH deficiency (GH peak <5 microg/liter). They were significantly shorter and younger at the time of diagnosis than those with normal magnetic resonance imaging, had better catch-up growth (+2.7 +/- 0.9 vs. +1.3 +/- 0.8 SD score; P < 0.01), and reached greater final height (-1.1 +/- 1.0 vs. -1.7 +/- 1.0 SD score; P < 0.05). Among patients with normal magnetic resonance imaging, there was no difference in catch-up growth and final height between partial and total GH deficiencies. GH-deficient subjects with normal magnetic resonance imaging and treated and untreated patients with idiopathic short stature had comparable auxological characteristics, age at evaluation, and target height. Although they had different catch-up growth (+1.3 +/- 0.8, +0.9 +/- 0.6, and +0.7 +/- 0.9 SD score, respectively; P < 0.01, by ANOVA), these patients reached a similar final height (-1.7 +/- 1.0, -2.1 +/- 0.8, and -2.1 +/- 1.0 SD score, respectively; P = 0.13). Pituitary magnetic resonance imaging findings show the heterogeneity within the group of nonacquired GH deficiency and help to predict the response to GH treatment in these patients. The similarities in growth between the GH-deficient children with normal magnetic resonance imaging and those with idiopathic short stature suggest that the short stature in the former subjects is at least partly due to factors other than GH deficiency.     

Treatment with growth hormone and luteinizing hormone releasing hormone analog improves final adult height in children with congenital adrenal hyperplasia

Final adult height is often compromised in children with congenital adrenal hyperplasia (CAH). This study examines the impact of GH and LHRH analog (LHRHa) on final adult height in patients with CAH due to 21-hydroxylase deficiency. Fourteen patients with CAH (eight males, six females) predicted to be more than 1.0 sd below their midparental target height received GH and LHRHa until final height. Each patient was matched at the start of GH therapy to a CAH patient treated only with glucocorticoids according to type of CAH, sex, and chronological age. Mean age, bone age, height, height prediction, and target height were the same in both groups at the beginning of GH therapy. Mean duration of GH treatment was 4.4 +/- 1.5 yr. Mean duration of LHRHa therapy was 4.2 +/- 2.0 yr. In the treatment group, final height sd score of -0.4 + 0.8 was significantly greater than both the initial prediction of -1.5 +/- 0.9 (P < 0.0001) and the final height sd score of the untreated group of -1.4 +/- 1.1 (P = 0.01). Our results indicate that the combination of GH and LHRHa improves final adult height in patients with CAH.