Growth of asthmatic children during treatment with budesonide: a double blind trial.

OBJECTIVE--To determine whether the inhaled glucocorticosteroid budesonide has any adverse effect on short term linear growth in children with mild asthma. SETTING--Outpatient clinic in secondary referral centre. PATIENTS--15 children aged 6-13 years with normal statural growth velocity during the previous year, no signs of puberty, and no use of systemic or topical steroids in the two months before the study. DESIGN OF INTERVENTIONS--Double blind, randomised crossover trial with two active periods in which budesonide was given in divided daily doses of 200 micrograms and 800 micrograms. During run in and two washout periods placebo was given. After the second washout period the children received open treatment with 400 micrograms budesonide daily. All periods were of 18 days'' duration. MAIN OUTCOME MEASURE--Growth of the lower leg as measured twice a week by knemometry. RESULTS--Mean growth velocity of the lower leg was 0.63 mm/week during run in and during washout 0.64 mm/week. Budesonide treatment was associated with a significant dose related reduction of growth velocity: the mean reduction in growth velocity during treatment was 0.11 (95% confidence interval -0.15 0.36 (0.13 to 0.59) mm/week with 800 micrograms budesonide (p less than 0.05; Page''s test). During treatment with 400 micrograms budesonide a reduction of 0.17 (-0.10 to 0.45) mm/week was found. CONCLUSIONS--Treatment with inhaled budesonide is associated with a dose related suppression of short term linear growth in children with mild asthma.     

Short-term growth after withdrawal of exogenous glucocorticoids

BACKGROUND: The growth-suppressive effect of systemic glucocorticoids in children is well established, however, recovery of growth after withdrawal of short-term treatment in school-age children has not been evaluated. OBJECTIVE: To assess short-term growth after withdrawal of systemic glucocorticoids. Methods: A post-hoc analysis of data from a double-blind lower leg growth trial which compared 5 mg prednisolone once daily in the evening with placebo was performed. The study consisted of run-in, treatment, wash-out and run-out periods of 1 week duration. In 10 children with asthma (mean age 11 years) lower leg growth measured with the knemometer could be studied up to 3 weeks after withdrawal of prednisolone. RESULTS: Mean (SEM) lower leg growth rates during run-in, prednisolone treatment and the first, second and third weeks after withdrawal of prednisolone were 0.48 (0.15), -0.27 (0.20), 0.53 (0.19), 0.72 (0.16) and 0.66 (0.14) mm/week, p < 0.001. Mean growth rates during run-in and the first, second and third weeks after withdrawal of prednisolone did not vary, p = 0.68. CONCLUSION: Recovery of suppressed lower leg growth rates occurs within a week after withdrawal of exogenous glucocorticoids.     

Serum zinc and somatic growth in children with growth retardation

A possible role for zinc deficiency in some cases of growth retardation in southern France was investigated. Control values for zinc for 160 children (age=12.5±2.4 yr) are 0.85±0.22 mg/L (mean ±2 SD). Twenty-five children with low serum zinc values (<0.63 mg/L) and 25 matched short children with normal serum zinc values (>0.63 mg/L) were studied. Children in the two groups did not differ significantly in age, pubertal development, stature, and weight. For the 25 children whose serum values were low, we found significantly lower values for bone age delay, growth velocity in mm/month, as well as the ratio between calculated growth velocity and theoretical growth velocity for the bone age (so that zincemia was correlated to these parameters in the whole sample of 50 subjects). Nevertheless, no significant difference could be found between the two groups for serum somatomedin C, serum osteocalcin values, and GH responses to the GH stimulatory tests (exercise test, overnight sampling, insulin-induced hypoglycemia, arginine test). Therefore, low serum zinc is associated with a retardation in both somatic growth and pubertal maturation.     

Final height in children with idiopathic growth hormone deficiency treated with a fixed dose of recombinant growth hormone

There is no consensus regarding the optimal dosing of recombinant human growth hormone (rhGH) for children with growth hormone deficiency (GHD). Our objective was to evaluate the final adult height (FAH) in children with idiopathic GHD treated with a fixed rhGH dose of 0.18 mg/kg/week. We reviewed all charts of patients with idiopathic GHD treated with rhGH since 1985 who reached FAH. Ninety-six patients were treated for an average of 5.4 years. The mean age was 11.9 years, the mean height -2.87 standard deviation score (SDS) and the mean FAH was -1.04 SDS. Females had a lower predicted adult height than males at the initiation of therapy (-2.0 vs. -1.01 SDS; p = 0.0087) but a higher FAH - predicted adult height (1.08 vs. 0.04 SDS; p = 0.0026). In multiple regression analysis, the FAH SDS was positively related to the midparental height SDS, the height SDS at GH initiation and growth velocity during the first year of therapy, and negatively correlated with peak GH and bone age at initiation (r(2) = 0.51; p < 0.005). Treatment of children with idiopathic GHD with a fixed dose of 0.18 mg/kg/week rhGH is sufficient to reach FAH within 2 SDS of the normal population range (84%) with an average FAH within -0.5 SDS of midparental height.     

Short-term growth response to GH treatment and considerations upon the limits of short-term growth predictions

OBJECTIVES: To investigate the impact of short-term growth measurements on predicting the individual growth response to GH treatment, and to elucidate the possible reasons for the limited accuracy of current growth prediction models for GH-treated children. METHODS: Short-term growth measurements by knemometry and stadiometer in 99 short, GH-treated children (27 girls, 72 boys), aged 10.3 +/- 2.3 years, from the Children's University Hospital, Leipzig, Germany. RESULTS: GH treatment significantly accelerated the mean height velocity (HV) from 4.3 +/- 1.0 to 8.1 +/- 1.8 cm/year during the first year of treatment, the average height standard deviation score (SDS) shifted by +0.52 SD. The variation in HV also increased, from S(2) = 1.0 before to S(2) = 3.4 cm(2)/year(2) during treatment. Lower leg length (LLL) velocity accelerated from 1.6 +/- 0.7 before treatment to 3.4 +/- 1.0 cm/year during the first 8 weeks of treatment. Four coefficients of correlation appeared clinically meaningful: (1) LLL velocity vs. body HV during the first year of GH treatment (r = 0.87), indicating that GH acts simultaneously on leg and rump growth; (2) early (first 8 weeks) LLL velocity vs. 1-year body HV during treatment, with r = 0.61 (R(2) = 0.38), indicating that 38% of the variation in HV during the first year of treatment is already predictable by an initial 8-week period of knemometry; (3) early (first 8 weeks) LLL velocity vs. 1-year LLL velocity during treatment, with r = 0.63 (R(2) = 0.39), and (4) early (first 8 weeks) LLL velocity vs. later LLL velocity, up to the end of the first year, with r = 0.53 (R(2) = 0.28) indicating that the early response on lower leg growth persists for at least 1 year of GH treatment. CONCLUSIONS: (1) Thirty-eight percent of the variation in HV during the first year of GH treatment is predictable by an initial 8-week period of knemometry. This parallels early changes in biochemical markers of bone turnover after GH treatment. (2) There is evidence for a baseline variability in HV both in healthy children and in children with growth disorders that make growth prediction difficult.     

Short-term effect on growth of two doses of GRF 1-44 in children with growth hormone deficiency: comparison with growth induced by methionyl-GH administration

In a double-blind study 12 prepubertal children with idiopathic growth hormone (GH) deficiency were treated with growth hormone releasing factor (GRF) 1-44 in a dosage of 7.5 or 15 micrograms/kg body weight, administered once a day subcutaneously. With 7.5 micrograms/kg the average growth velocity increased from 2.5 to 4.6 cm/year, an insufficient response. With the higher dosage the average growth velocity increased from 2.7 to 7.0 cm/year, a similar increase as observed with GH therapy in subsequent periods. In 3 of the 6 children treated with the higher dose appropriate catch-up growth was observed. The growth response of the lower leg length was not always consistent with the statural growth response.     

Plasma somatomedin activity and urinary hydroxyproline excretion during administration of human growth hormone in children with short stature. Long-term effects and relation with short-term changes

Growth velocity, somatomedin activity (SM-act) and total urinary hydroxyproline excretion (THP) were studied in 9 prepubertal short children on long-term human growth hormone (hGH) therapy, and compared to the short-term responses to hGH, described in the accompanying paper. Positive correlations were found between the short-term increases of either SM-act or THP and growth acceleration, but these were too weak to be used as a predictor. On a schedule of biweekly injections, pre-injection SM-act values were only slightly higher than pre-treatment values, but post-injection values were considerably higher and similar to the values obtained with comparable hGH doses in the short-term study. There was an excellent relationship of the increment of SM-act during chronic therapy over untreated values and the increases of growth velocity. During the first year on hGH therapy the mean SM-act, mean THP and growth acceleration showed strong correlations.     

Effect of different growth hormone dosages on the growth velocity in children born small for gestational age

To assess whether short-term growth hormone (GH) treatment can improve the linear growth in children who were born small for gestational age (SGA), we started a randomized multicenter trial in 26 age- and sex-matched prepubertal children born SGA. During the 1st year of GH therapy, all children received GH 0.23 mg/kg/week, then during the 2nd year, 13 children received the same dose (group A), and in the other 13 children, the dose of GH was doubled, i.e., 0.46 mg/kg/week (group B). During the 1st year of therapy, the growth velocity significantly (p<0.0001) increased in all patients. During the 2nd year, group A showed a significant decrease of the growth velocity (p<0.015), whereas group B maintained the growth rate. The height in group A children significantly increased during the 1st and the 2nd year of GH therapy (p<0.000002 and p<0.000001, respectively), reaching the normal range in 8 out of 13 children at the end of 2 years of GH therapy. The height in group B children significantly increased during the 1st and the 2nd year of GH therapy (p<0.000001 and p<0.000001, respectively), reaching the normal range in all 11 children who completed the GH therapy. The height gain was similar in groups A and B treated with the same GH dosage during the 1st year of therapy. A greater increase in height gain was found in children of group B treated with the higher GH dosage during the 2nd year of therapy as compared with group A (p<0.02). Significant increases in insulin-like growth factor I (p<0.0001), acid-labile subunit (p<0.0002), and bone/chronological age ratio (p<0.0001) were found after the 1st year of GH therapy, but no significant changes were observed during the 2nd year, independently of the GH dose. In conclusion, the height velocity of children born SGA significantly increases during the 1st year of GH therapy, diminishes, but can decrease during the 2nd year, if the GH dosage is not raised.     

Final height after growth hormone therapy in peripubertal boys with a subnormal integrated concentration of growth hormone.

The aim of this study was to test the effect of growth hormone (GH) therapy on final height in peripubertal boys with idiopathic short stature in whom a subnormal integrated concentration of GH (< 3.2 micrograms/l) was found. Twenty-eight peripubertal children were studied. Height was below 2 SD for age, growth velocity was < 4.5 cm/year, bone age was more than 2 SD below mean for age and GH response to provocative tests was more than 10 micrograms/l. Eleven subjects (group B) were treated with recombinant GH 0.75 unit/kg/week, divided into 3 weekly doses for 2 years, and then the same weekly dose divided into daily injections was administered until final height was attained. Seventeen untreated children (group A) who were followed until cessation of growth served as controls. The GH-treated patients reached their target heights (-2.1 +/- 0.5, mean +/- SD in SDS) and predicted heights (-1.8 +/- 0.8) determined by the Bayley and Pinneau method, while the final heights of the untreated patients were significantly lower than their target heights and their predicted final heights (-2.7 +/- 0.7, -1.8 +/- 1.0 and -2.7 +/- 0.7, respectively). The main effect of GH was observed during the 1st year of treatment when height velocity was significantly higher in the GH-treated group than in the untreated one (9.3 +/- 2.1 vs. 5.3 +/- 1.1, respectively, p < 0.001). The high cost of the treatment in this specific age group should be weighed against the results.     

Effects of zamic as a means for zinc supplementation in growing children

We investigated the effects of zinc supplementation in cases of moderate growth retardation in which GH treatment could not be used. Zamic (ZA, an association containing arginine, L-methionine, and zinc; from Aguettant pharmaceuticals) was compared with arginine aspartate (AA) (5 g) in a crossover randomized trial (6 mo of each treatment at random order over 1 yr). We present preliminary results of 24 children who completed the study (3 girls, 21 boys, age 9–13 yr). Subjects had to be prepubertal, with no GH deficiency diagnosed. In 15 subjects growth velocity was lower than 5 mm/mo: In this case ZA improved growth velocity (rising from 3.105 ± 0.229 to 5.4 ± 0.69 mm/mop < 0.01), whereas the effect of AA was not significant. The increase in growth velocity was higher with ZA (+2.44 ±0.657 mm/mo) than AA (+0.438 ± 0.450 mm/mo)p < 0.05. These results suggest that ZA is more efficient than AA, consistent with the hypothesis that zinc needs are increased in those children in this period of life.     

Pubertal growth spurt induced by human chorionic gonadotropin in hypogonadotropic growth hormone-deficient children

Eight hypogonadotropic growth hormone-deficient children were treated with human chorionic gonadotropin (HCG) while they continued to receive a fixed dose of HGH for a one year period. They were observed for changes in somatomedin C (IGF-I) and height increase velocity. Mean somatomedin C was 0.79 +/- 0.30 U/ml in normal prepubertal children (N = 7) and 0.78 +/- 0.31 U/ml in prepubertal normal short children (N = 22). At pubertal stage 3, somatomedin C was 2.21 +/- 1.23 and 2.05 +/- 0.44 U/ml in normals (N = 5) and in normal short children (N = 7), respectively. When 3000-5000 units/week of HCG were given to each of the 8 hypogonadotropic growth hormone-deficient children who were receiving HGH at a mean dose of 0.33 +/- 0.05 IU/kg/week, testosterone increased from less than 0.3 ng/ml to more than 5 ng/ml at 6 months in 3 cases and at 12 months in 2 cases, while the testosterone concentration was less than 3.5 ng/ml in the remaining 3 cases. The rate of height increase rose significantly (p less than 0.001) from 5.2 +/- 1.0 to 9.3 +/- 1.4 cm/year mimicking the normal pubertal growth spurt. However, the mean somatomedin C concentration was 0.44 +/- 0.23 before therapy, 0.33 +/- 0.30 at 6 months and 0.31 +/- 0.14 U/ml at 12 months after the start of HCG therapy. It is concluded that the pubertal growth spurt induced by HCG in hypogonodotropic GH-deficient male children is not mediated by the increase in somatomedin C production.     

Analysis of differential growth of the right and the left leg

In spite of well documented standards for length and annual growth rates of the femur and tibia, there is little information on short term longitudinal bone growth. We investigated differential growth dynamics of the lower leg in 10 children, aged 6:3 to 14:2 years, by knemometry, a novel and non-invasive technique of accurate lower leg length measurement with a technical error of 0.09 to 0.16 mm. Mini growth spurts were detectable in 7 of the children and occurred synchroneously in both legs. Approximately half of the variance of the weekly lower leg length increments could be attributed to synchrony of leg length increments, but a significant amount of residual variance remained which exceeded the technical error of the measurements. Run-analysis of the individual series of right vs. left differences of the weekly lower leg length increments provided evidence for alternating periods of overgrowth of one leg compared to the contralateral side in 5 out of the 10 children. We concluded that there is suggestive evidence of partial independence of lower leg growth in the short term.     

Maximal strength testing in healthy children

Strength training has become an accepted method of conditioning in children. However, there is concern among some observers that maximal strength testing may be inappropriate or potentially injurious to children. The purpose of this study was to evaluate the safety and efficacy of 1 repetition maximum (1RM) strength testing in healthy children. Thirty-two girls and 64 boys between 6.2 and 12.3 years of age (mean age 9.3 +/- 1.6 years) volunteered to participate in this study. All subjects were screened for medical conditions that could worsen during maximal strength testing. Under close supervision by qualified professionals, each subject performed a 1RM test on 1 upper-body (standing chest press or seated chest press) and 1 lower-body (leg press or leg extension) exercise using child-size weight training machines. No injuries occurred during the study period, and the testing protocol was well tolerated by the subjects. No gender differences were found for any upper- or lower-body strength test. These findings demonstrate that healthy children can safely perform 1RM strength tests, provided that appropriate procedures are followed.     

Effect of growth hormone on short normal children.

The growth of 26 short normal prepubertal children (mean age 8.4, height velocity standard deviation score for chronological age between +0.4 and -0.8) was studied for two years. Sixteen children were treated with somatrem (methionyl growth hormone) during the second year, and the remaining 10 children served as controls. During one year of treatment the height velocity standard deviation score for chronological age increased from the pretreatment mean of -0.44 (SD 0.33) to +2.20 (1.03). These values represented a change in height velocity from a pretreatment mean of 5.3 cm/year (range 4.6-6.9) to 7.4 cm/year (range 5.7-9.9). In the control group the height velocity standard deviation score was unchanged. Bone age advanced by 0.75 (0.33) years in the treated group compared with 0.70 (0.18) years in the control group. There was a significant increase in the height standard deviation score for bone age (0.63 (0.55] in the treated group. Multiple regression analysis of predictive factors contributing to the change in height velocity standard deviation score over the first year of treatment showed that the dose of growth hormone and pretreatment height velocity standard deviation score were important, together yielding a regression correlation coefficient of 0.80. The only metabolic side effect of treatment was an increase in fasting insulin concentration, which may be an important mediator of the anabolic effects of growth hormone. Treatment had no effect on thyroid function, blood pressure, or glucose tolerance. At the end of the treatment year seven of the 16 treated children had developed antibodies to growth hormone, but they were present in low titre with low binding capacity and in no child was growth attenuated. Biosynthetic growth hormone improved the height velocity of children growing along or parallel to the third height centile, but the effects on height prognosis need to be assessed over a longer period.     

Medium-term cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children

AIM: To investigate the possible cardiac morphofunctional alterations inducd by prolonged and high-dose GH therapy in a group of 14 children with isolated GH deficiency. PATIENTS AND METHODS: Patients were evaluated at phase 1, after 1.1 +/- 0.6 years of treatment with GH 0.93 +/- 0.13 U/kg/week, and at phase 2, after 5.5 +/- 2.1 years of therapy 0.89 +/- 0.11 U/kg/week. At each phase left ventricular volume, mass and systolic function were evaluated by two-dimensional guided M-mode echocardiography; left ventricular diastolic function was assessed by PW-Doppler sampling of transmitral flow. RESULTS: Phase 1: diastolic blood pressure was lower (p < 0.05) and fractional shortening was not adequate for the level of afterload (stress shortening index p < 0.05) in patients compared to controls. Phase 2: diastolic blood pressure was lower (p < 0.01) and mass and mass/volume ratio were increased (mass index p < 0.05, mass/ volume ratio p < 0.05) in patients compared to controls. The increased mass/volume ratio, together with the normal systolic blood pressure, explains the reduction in peak systolic stress (p < 0.005). Among the parameters of left ventricular diastolic function, the peak E velocity/total area under mitral valve tracing and the area under E velocity/total area under mitral value tracing ratios were significantly decreased (p < 0.05). CONCLUSION: After a mean period of 5 years on high-dose GH treatment in GH-deficient children, subclinical morphofunctional alterations in the left ventricle were found.     

Continuous measurement of biparietal distance in the intact and hypophysectomized fetal sheep using ultrasound

Piezoelectric transducers were implanted into the parietal bones of intact (n = 4) and hypophysectomized (n = 8) fetal sheep of approximately 110-120 days gestational age (term 145-150 days). Intertransducer distance was determined by measuring the time taken for an ultrasonic pulse, generated by one transducer, to elicit a piezoelectric response in an opposing transducer. The limit of sensitivity of the timer was +/- 0.033 microsec. The ultrasonic velocity through fetal sheep brain tissue was 1549.6 +/- 2.2 m.s-1 (SEM; n = 33). This velocity remained constant throughout the entire period studied in both intact and hypophysectomized fetuses. At this velocity, the sensitivity of the measuring device was +/- 0.05mm. The ultrasonic transit time was measured daily between 0900 and 1100h until term in all fetuses. Three hypophysectomized fetuses were allowed to remain in utero until day 163 of gestation. The mean biparietal distance growth rate prior to day 135 for the intact and hypophysectomized fetuses was 0.25 +/- 0.03 and 0.27 +/- 0.025 mm/day respectively. These values were not significantly different (P greater than 0.05). A significant decrease (P less than 0.05) in growth rate was detected in both experimental groups between days 135 and 147 and was more pronounced in the sham (0.05 +/- 0.04 mm/day) than in the hypophysectomized (0.14 +/- 0.03 mm/day) group. However, the growth rate of the sham animals after day 135 was not significantly different from that of the hypophysectomized animals. In the three hypophysectomized fetuses killed at day 163 the biparietal distance growth was maintained at 0.12 +/- 0.005 mm/day. We conclude that fetal biparietal distance growth is pituitary independent from day 110 of gestation and that this technique for measuring distance is a valid and extremely accurate method for the continuous measurement of this parameter of fetal growth and may have further applications in other areas of growth research.     

Differential effects of short-term prednisolone treatment on peripheral and abdominal subcutaneous thickness in children assessed by ultrasound

Long-term glucocorticoid excess decreases peripheral and increases abdominal subcutaneous thickness. Short-term prednisolone treatment is used in the treatment of many acute and chronic conditions in children. The aim of the present study was to elucidate if changes in thickness of cutis, subcutis, or dermal water content may be induced by short-term prednisolone treatment in children.Twenty children with asthma aged 7.7-13.8 years were included in a double-blind, randomized, placebo-controlled crossover trial. Active treatment was 5mg prednisolone daily. Treatment, run-in, and wash-out periods were 1 week. On days 1 and 7 of each treatment period, 20 MHz ultrasound scanning of the skin was performed on the thigh, forearm, and abdomen.Prednisolone treatment was associated with decreases in the total thickness of the cutis and subcutis in the thigh (0.28 mm) and forearm (0.15 mm), and an increase in the abdomen (0.23 mm). During placebo treatment the thickness was increased in the thigh (0.07 mm) and abdomen (0.05 mm), and reduced in the forearm (0.03 mm). The differences between prednisolone and placebo treatment were statistically significant in the thigh (P=0.04). The increase in thickness in the abdomen during prednisolone treatment was statistically significantly different from the reductions in the thigh (P=0.03) and forearm (P=0.05). There were no statistically significant differences in the dermal thickness or water content during prednisolone treatment compared to placebo.Short-term treatment with 5mg prednisolone daily may cause differential effects in peripheral and abdominal subcutaneous thickness in children.     

Effects of acute intravenous injection of two growth hormone-releasing hormones (GHRH 1-40 and 1-29) on serum growth hormone and other pituitary hormones in short children with pulsatile growth hormone secretion

We administered two different growth hormone-releasing hormones (GHRH) to 20 short, prepubertal children who had spontaneous secretion of growth hormone (GH), assessed from 24-hour GH secretion profiles (72 sampling periods of 20 min). We compared one i.v. injection of 1 microgram/kg of GHRH 1-40 with that of GHRH 1-29 regarding serum concentrations of GH, prolactin, luteinizing hormone, follicle-stimulating hormone and IGF-I. The children were allocated to two groups without statistical randomization. Both groups were given both peptides, with at least 1 week in between. The first group started with GHRH 1-40, the other with GHRH 1-29. The peptides both induced an increased serum concentration of GH of the same magnitude: mean maximal peak of 89 +/- 12 mU/l after GHRH 1-40 and 94 +/- 10 mU/l after GHRH 1-29 (n.s.). The mean difference in maximum serum GH concentration in each child after injection was 52 +/- 9 mU/l, range 1-153 mU/l. GHRH 1-29 also induced a short-term, small increase in the concentrations of prolactin (p less than 0.05), luteinizing hormone (p less than 0.01) and follicle-stimulating hormone (p less than 0.05). We conclude that the shorter sequence GHRH 1-29, when given in a dose of 1 microgram/kg, gives a rise in serum concentration of GH similar to that after the native form GHRH 1-40.     

Greater efficiency of human growth hormone therapy in children below five years of age with growth hormone deficiency. A 5-year follow-up study

The effect of human growth hormone (hGH) therapy was studied in 39 prepubertal children with growth hormone deficiency (24 with isolated growth hormone deficiency; 15 with multiple pituitary hormone deficiencies) who had been treated for 2-5 years. They were divided into two groups according to age at the initiation of therapy: group A (n = 21), 0.7-4.8 years (mean chronological age, 2.9 +/- 1.4 years, and bone age, 1.2 +/- 0.9 years); group B (n = 18), 5.2-9.9 years (mean chronological age, 7.4 +/- 1.3 years, and bone age, 4.0 +/- 1.5 years). hGH was given at an initial dose of 2-4 IU 3 times/week, raised to 4-6 IU 3 times/week when growth velocity slowed. In the first year, the mean height SDS gain was 1.7 for group A and 0.8 for group B, and in the second year, 1.1 and 0.1, respectively. Subsequently this remained consistent. Bone age advancement was significantly slower in the younger group (3.8 vs. 5.8 years during 5 years) although this group had a greater catch-up response to therapy. It is concluded that hGH therapy is significantly more effective in achieving normalization of height when treatment is initiated at an early age.     

Growth after radiotherapy and chemotherapy in children with leukemia or lymphoma.

The effect of radio- and chemotherapy on auxological parameters was investigated in 30 children treated for acute lymphatic leukemia (ALL) or non-Hodgkins lymphoma (NHL). Growth velocity was decreased during the first year of treatment. Catch-up growth was insufficient during the following years. Thus, the whole group experienced a loss of height of 0.49 +/- 1.1 SD at 6.8 +/- 2.6 years after diagnosis. Height and growth velocity were not different between children who received 18 or 24 Gy cranial irradiation; however, growth velocity was significantly lower in children who were treated for more than 2 years or who had the more intensive chemotherapeutic protocol. Evaluation of the growth hormone (GH) response to pharmacological stimulation revealed reduced GH peaks in 47% of the patients, but there was no correlation of GH peak with growth or treatment parameters. In conclusion, the impairment of growth in children after treatment for ALL or NHL might be related to the intensity and duration of chemotherapy.