Improved growth response to GH treatment in irradiated children

The growth response to two years of GH treatment was studied in fifteen children after radiotherapy for a cranial tumor. The growth response was compared to that of short children (-2 SD) and that of children with idiopathic growth hormone deficiency (GHD) of similar ages. All children were treated with hGH 0.1 IU/kg/day s.c.; which is a higher dose and frequency than previously reported for irradiated children. On this protocol the growth rate increased 5.0 +/- 0.5 cm/y (mean +/- SEM) the first year and 3.8 +/- 0.7 cm/y the second year compared to the growth rate the year before GH-treatment. Although the net gain in growth was higher than previously reported, the first year growth response was significantly reduced (p less than 0.05) compared to that of GHD-children (7.6 +/- 0.5 cm/y) but exceeded (p less than 0.05) that of short children (3.4 +/- 0.3 cm/y). The median spontaneous 24 h-GH secretion was 209 mU/l in the short children, 52 mU/l in the irradiated children and 16 mU/l in the idiopathic GHD children. Thus the growth increment varied inversely to the spontaneous GH secretion observed in the three groups.     

Linear growth response to exogenous growth hormone in children with short stature

Response to growth hormone (GH) therapy was evaluated in 38 short children (28 males and 10 females; less than 1% in height for chronologic age [CA]) who were clinically categorized into three groups based on their endogenous mean 24-hour GH concentration (mean 24-hour GH) and peak GH response to two or more provocative agents (peak GH). All patients were treated with biosynthetic somatropin (human growth hormone) (0.15 to 0.30 mg/kg per week) injected subcutaneously three to seven times per week for a mean duration of 12.5 months. Group 1 consisted of 17 subjects (CA, 12.5 +/- 2.9 years [mean +/- SD]; bone age, 9.4 +/- 2.9 years; height velocity [HV], 3.4 +/- 1.8 cm/y; peak GH, 5.8 +/- 2.6 micrograms/L; mean 24-hour GH, 1.7 +/- 0.6 micrograms/L; and insulinlike growth factor-I, 0.40 +/- 0.24 U/mL. Group 2 consisted of 10 subjects (CA, 11.7 +/- 2.7 years; bone age, 9.2 +/- 3.0 years; HV, 3.4 +/- 1.6 cm/y; peak GH, 16.4 +/- 5.2 micrograms/L; mean 24-hour GH, 1.7 +/- 0.5 micrograms/L; and insulinlike growth factor-I, 0.49 +/- 0.27 U/mL. Group 3 consisted of 11 subjects (CA, 12.7 +/- 2.2 years; bone age, 10.2 +/- 2.4 years; HV, 3.5 +/- 1.5 cm/y; peak GH, 22.5 +/- 8.6 micrograms/L; mean 24-hour GH, 3.8 +/- 1.1 micrograms/L; and insulinlike growth factor-I, 1.07 +/- 0.69 U/mL. Following administration of somatropin, an increase (delta) in HV of 2.0 cm/y or greater occurred in 94% (16/17) of the group I subjects (delta HV of 5.1 +/- 2.6 cm/y), in 90% (9/10) of the group 2 subjects (delta HV of 4.3 +/- 2.2 cm/y), and in 73% (8/11) of group 3 subjects (delta HV of 3.7 +/- 2.3 cm/y). However, regardless of provoked and/or endogenous GH secretory dynamics, 88% of the children whose pretreatment HV was 2.0 cm/y or less, 94% whose pretreatment HV was between 2.0 and 4.0 cm/y, and 79% whose pretreatment HV was greater than 4.0 cm/y increased their HVs to 2.0 cm/y or greater while they were receiving somatropin. Significant negative correlations were observed between delta HV and pretreatment HV (r = -.67), delta HV and GH concentration expressed as a 24-hour area under the curve (r = -.33), and delta HV and peak GH (r = -.34).(ABSTRACT TRUNCATED AT 400 WORDS)     

Treatment of children with Down syndrome and growth retardation with recombinant human growth hormone.

The effect of recombinant human growth hormone on children with Down syndrome who had growth retardation and microcephaly was examined. Thirteen children with trisomy 21 without congenital heart disease who were short for age (-1.19 to -3.5 standard deviation score) and microcephalic (-1.58 to -6.60 standard deviation score) were given recombinant human growth hormone, 0.1 mg/kg subcutaneously, 3 days a week for 1 year. Before treatment, peak serum growth hormone concentrations were less than 10 micrograms/L after levodopa and clonidine stimulation tests in five patients, after clonidine in three patients, and after levodopa in three patients. Three patients had nocturnal integrated growth hormone concentrations of 0.5, 1.5 and 0.65 micrograms/L, respectively. The mean growth rate before treatment was 5.4 +/- 1.6 cm/yr and increased to 12.2 +/- 3.2 cm/yr (p less than 0.001) after 12 months of recombinant human growth hormone treatment. The mean head circumference standard deviation score before treatment was -3.1 +/- 1.3 and increased to -2.3 +/- 1.2 (p less than 0.001) at 12 months. Bone age before and 1 year after treatment increased in correspondence with chronologic age. Plasma hemoglobin A1c concentration was normal during treatment with recombinant human growth hormone. The mean plasma concentrations of insulin-like growth factor I at baseline and at 12 months were 0.54 +/- 0.19 U/ml and 1.25 +/- 0.97 U/ml, respectively (p less than 0.02). We conclude that recombinant human growth hormone therapy can result in a significant increase in annual growth rate and head circumference in children with Down syndrome, without significant side effects.     

Stimulation of collagen synthesis and linear growth by growth hormone in glucocorticoid-treated children.

Impaired linear growth and skeletal maturation associated with chronic glucocorticoid therapy may result from (1) inhibited insulin-like growth factor 1 (IGF-1) activity; (2) impaired type 1 collagen synthesis; or (3) suppressed growth hormone (GH) secretory response to growth hormone-releasing hormone. Each mechanism could potentially be improved by exogenous GH treatment. Seven slowly growing glucocorticoid-treated children received recombinant DNA human GH (0.3 mg/kg/per week) for 6 to 21 (mean 13.1 +/- 4.9) months. Height, weight, IGF-1 activity, glycosylated hemoglobin level, and C-terminal type 1 procollagen level were measured every 3 months and growth velocity was calculated. Skeletal maturation and 2-hour postprandial serum glucose and insulin levels were assessed every 6 months. All patients showed increased growth velocity during treatment with GH. Mean growth velocity increased from 3.43 +/- 0.65 cm/y to 6.72 +/- 0.84 cm/y with GH therapy (P less than .005). Growth velocity standard deviation scores corrected for bone age (P less than .005), IGF-1 levels (P less than .05), and C-terminal type 1 procollagen levels (P less than .005) also increased with GH therapy. C-terminal type 1 procollagen levels correlated well with growth velocity (r = .652) while IGF-1 levels did not (r = .17). Glycosylated hemoglobin levels remained unchanged, but 2-hour postprandial glucose levels rose during GH treatment. Slowly growing glucocorticoid-treated children receiving GH therapy increased growth velocity for 6 to 21 months. Initially diminished C-terminal type 1 procollagen levels rose with GH therapy, a change which corresponded with growth acceleration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Accelerated growth after recombinant human growth hormone treatment of children with chronic renal failure

We studied the effect of recombinant human growth hormone treatment on five boys, aged 4.6 +/- 1.8 years, who had chronic renal failure secondary to congenital renal diseases (mean creatinine clearance (+/- SD): 18.3 +/- 6.3 ml/min/1.73 m2 (0.32 +/- 0.11 ml/sec/1.73 m2]. Patients received 0.125 mg/kg of growth hormone three times per week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 4.9 +/- 1.4 cm/yr (range 3.0 to 6.3 cm/yr), with a mean standard deviation score for a height of -2.98 +/- 0.73 (range -2.16 to -3.59). At the end of therapy, the mean growth velocity had increased to 8.9 +/- 1.2 cm/yr (range 7.5 to 10.7 cm/yr), and the mean height standard deviation score improved to -2.36 +/- 0.83 (range -1.15 to -3.18). Bone age advancement was consistent with the period of growth. Routine laboratory determinations, including results of glucose tolerance testing, did not vary significantly from pretreatment levels. These preliminary data indicate that growth-retarded children with chronic renal failure can respond to exogenous growth hormone therapy with a marked acceleration in growth velocity.     

Zinc deficiency: a contributing factor of short stature in growth hormone deficient children

Zinc is an essential trace element which affects growth by promoting DNA and RNA synthesis and cell division. Zinc deficiency causes growth retardation and its frequency is high in developing countries. It could contribute to the effect of growth hormone (GH) treatment in GH deficient children. In this study, we investigated zinc deficiency in GH children. Twenty-four GH deficient children (treated with GH for 2.2 +/- 1.6 years) were recruited for the study. Intracellular erythrocyte zinc levels were measured. Eleven (45.9 per cent) were found to be zinc deficient (Group 1), while 13 patients (54.1 per cent) had normal zinc levels (Group 2). The mean growth velocity was 5.98 +/- 0.8 cm/year in Group 1 and 6.9 +/- 1.4 cm/year in Group 2. Group 2 was given oral zinc supplementation with a resultant growth velocity of 7.51 +/- 0.5 cm/year. During GH treatment in GH deficient children, zinc status should be evaluated as severe zinc deficiency could affect the response to GH treatment.     

Effect of somatotropin of mammalian cell origin in growth hormone deficiency.

Sixty-nine growth hormone-deficient patients were treated for 1 year with somatotropin (recombinant DNA-derived human growth hormone) produced in mouse cells. The growth velocity of the 50 patients (72%) in whom the effectiveness of this growth hormone could be evaluated increased from a mean (+/- SD) of 3.5 +/- 1.1 to 8.7 +/- 1.6. cm/y. An enhanced rate of weight gain was also observed. Bone age was not unduly accelerated. One of 66 patients developed antibodies to recombinant growth hormone, which did not affect the response to therapy. No patient developed antibodies to host cell proteins. An increased insulin response to a standard glucose load, without any change in glucose tolerance, was observed after 1 year of treatment. This authentic sequence human growth hormone preparation produced in mammalian cells is both effective and safe in the treatment of children with growth hormone deficiency.     

Evaluation of growth hormone secretion after completion of therapy

BACKGROUND: Growth hormone (GH) reserve in young adults previously diagnosed as having GH insufficiency, who were treated with human (h)GH replacement in childhood needs confirmation in adulthood. METHODS: Nine patients (seven males, two females; two empty cella, one hypoplasia of the hypophysis and six with idiopathic GH deficiency) diagnosed as having GH insufficiency by the insulin tolerance test (ITT) and dopamine stimulation test in childhood (mean age 12.8+/-2.6 years) were retested at completion of linear growth (mean age 21.0+/-3.0 years), 4.6+/-1.6 years after discontinuation of hGH therapy. RESULTS: At the initial diagnosis, seven had complete and two had partial GH deficiency. At diagnosis, the mean peak GH response to ITT and dopamine was 4.8+/-4.08 and 3.4+/-2.9 mU/L, respectively. At retesting, the mean GH response to ITT and dopamine stimulation was 3.5+/-2.5 and 3.3+/-3.1 mU/L, respectively (P=0.91 and 0.96, respectively). During hGH therapy, mean height velocity increased from 3.5+/-1.9 cm/year at diagnosis to 9.9+/-3.64 cm/year during the first year (P=0.002). One of nine children diagnosed as having GH insufficiency who was treated with hGH replacement had normal growth hormone secretion at completion of linear growth. CONCLUSIONS: All GH-insufficient children should be retested after completion of their hGH treatment and linear growth to identify those who are truly GH insufficient and who may benefit from GH therapy in adulthood.     

Therapy in short children with subnormal integrated concentrations of growth hormone

We evaluated the effect of growth hormone (GH) therapy on the posttreatment growth of 11 poorly growing children who had normal GH response to provocative stimuli but subnormal integrated concentrations of GH. Patients received 0.1 U/kg of GH three times per week. Their mean (+/- SD) growth rate increased from 3.3 +/- 1.0 cm/y before treatment to 6.5 +/- 1.4 cm/y after eight months of treatment. The growth rates of five patients declined to below 4.5 cm/y four months after treatment. Three of these patients resumed GH therapy and again responded with increased growth velocity (8.0 +/- 1.2 cm/y). After therapy, the growth rate of five remaining patients continued to be greater than 4.5 cm/y (6.8 +/- 1.4 cm/y). Two of these patients had entered puberty and their posttreatment growth rate might have been due to a pubertal growth spurt. The three prepubertal patients in this group had a gradual decline in growth velocity to 3.8 +/- 1.0 cm/y by the end of 12 posttreatment months. We conclude that maintenance of normal growth in patients with this pattern of GH deficiency is dependent on GH replacement therapy.     

Authentic recombinant human growth hormone. Results of a multicenter clinical trial in patients with growth hormone deficiency

197 patients with growth hormone deficiency (144 boys, 53 girls, age 1.5-19.5 [mean 11 +/- 3.6], bone age 0.3-15 [mean 8.9 +/- 3.5] years) were treated for one year with authentic recombinant human growth hormone (r-hGH, Norditropin] in several European paediatric centers. 107 patients were newly treated (group A), and 90 transferred from pituitary or methionine hGH (groups B and C). In 19 of the latter, treatment was interrupted for 6 months (group B), in the others, it was changed without interruption (group C). The dosage was 0.45 +/- 0.2 IU/kg/week given s.c. 6-7 times a week. Height velocity increased from 4.1 +/- 2.4 to 8.3 +/- 2.5 (group A), 2.6 +/- 1.8 to 8.3 +/- 2.3 (group B), and 6.2 +/- 2.7 to 6.8 +/- 2.2 cm/year (group C). Few patients complained of local discomfort at the injection site, but this disappeared after changing metacresol in the solvent to 0.9% benzyl alcohol. Only 3 patients developed antibodies to hGH in low titers, which did not interfere with growth. No changes in E. coli protein antibodies were observed. It is concluded that r-hGH is an efficient and safe treatment for children with growth hormone deficiency.     

Recombinant human growth hormone treatment in children with thalassemia major

BACKGROUND: To evaluate the growth hormone reserve and the growth hormone response to recombinant human growth hormone (GH) in prepubertal thalassemic children with growth retardation. METHODS: Twenty thalassemic patients with short stature and delayed bone age were studied. Patients were randomized into GH-treated (n = 10) and non-GH treated (control; n = 10) groups. The GH-treated group received recombinant human (rh)-GH (Genotropin) at the dose of 0.7 IU/kg per week for 12 months. RESULTS: There was a significant discordance between GH response to pharmacologic stimuli and physiological secretion of GH/GHRH testing. Following the administration of rhGH, growth velocity increased from 2.47 +/- 0.48 cm/year to 6.27 +/- 0.76 cm/year (P = 0.005), whereas there was not a similar change in the non-GH-treated group. The height velocities of the two groups during the 1 year follow-up period were significantly different (6.27 +/- 0.76 vs 3.99 +/- 0.34 cm/year; P = 0.025). There were significant differences between the height velocity improvements and height velocity standard deviation scores of the two groups as well. CONCLUSION: The present study has demonstrated that rhGH is a safe and efficacious mode of treatment in thalassemic children.     

Growth-stimulating effects of human growth hormone therapy in patients with Turner syndrome

We determined the effect of pituitary human growth hormone treatment on the growth rate of 52 children with Turner syndrome. The pretreatment growth rate was 3.2 +/- 0.8 cm/yr. Growth hormone treatment (0.2 IU/kg three times per week) resulted in enhancement of the growth rate to 5.9 +/- 1.4 cm/yr for the first year of therapy. The bone age advanced approximately 1 year during the year of therapy. The growth hormone therapy was discontinued at 12 months, and the mean growth rate decreased to pretreatment levels, 3.1 +/- 1.9 cm/yr; 26 of 41 patients actually had post-treatment growth rates that were less than the pretreatment rate. Glucose tolerance tests at 6-month intervals did not indicate an effect of hGH treatment on glucose intolerance. Several patients had glucose intolerance that preceded hGH treatment, but this remained stable during treatment; glucose intolerance likely was related to obesity in this group of patients. Basal and hGH-stimulated somatomedin C levels (32 patients) correlated with age of the patient but not with growth rate during therapy. We conclude that hGH therapy can accelerate the growth rate of patients with Turner syndrome. The growth rate increased to "normal" levels and was dependent on continued treatment with hGH. If the response continues, long-term treatment of Turner syndrome may result in increased adult height.     

Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone

Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 +/- 0.3 versus 3.4 +/- 0.2 micrograms/L); group 2 had significantly lower GH concentrations (1.6 +/- 0.2 micrograms/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 +/- 2.6 nmol/L, p less than 0.001) than in groups 2 and 3 (2.6 +/- 0.5 and 5.5 +/- 0.7 nmol/L, respectively). Urinary GH (mean +/- SEM) standardized for body weight (micrograms/kg) in group 1 (0.31 +/- 0.02) was significantly greater than in group 2 (0.14 +/- 0.01) and group 3 (0.20 +/- 0.01). However, when expressed as microgram/mol creatinine, the output of GH was similar in group 1 (4.0 +/- 0.3) and group 3 (3.4 +/- 0.3); both groups had significantly greater output compared to group 2 (1.3 +/- 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 +/- 0.02) was significantly greater than in group 2 (0.12 +/- 0.01) or group 3 (0.07 +/- 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p less than 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.     

Growth hormone secretory dynamics in children with precocious puberty

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.     

Predictors of growth response to growth hormone in otherwise normal short children.

Sixty prepubertal short children (39 boys) with heights less than 2 SD for age and gender were treated daily for 1 year with recombinant human growth hormone (GH), either 0.1 IU/kg (group 0.1, n = 32) or 0.05 IU/kg (group 0.05, n = 28). Reserve of GH was determined by at least one GH provocative stimulus and 24-hour continuous blood withdrawal to determine the integrated concentration of GH (IC-GH). All participants had a GH response to provocative tests greater than 10 micrograms/L. The height velocity (mean +/- SD) of the group as a whole increased from 4.46 +/- 1.02 to 7.59 +/- 1.65 cm/yr (p less than 0.001). The growth velocity of group 0.1 was significantly greater than that of group 0.05 (8.1 +/- 1.5 vs 7.0 +/- 1.65 cm/yr; p less than 0.01). Bone age did not advance more than 1 year during the treatment period. Growth velocity after 1 year of GH therapy was inversely correlated with the IC-GH in both groups, as was the pretreatment height velocity. We found no correlation of growth velocity during GH therapy with other measures such as parental heights, bone age/chronologic age ratio, maximal GH response to provocative tests, chronologic age, or pretreatment insulin-like growth factor I levels. We conclude that the best predictors for the 1-year growth outcome of short children with a normal GH response to provocative tests are the pretreatment growth velocity and the IC-GH. The short-term benefit from GH therapy in children with a normal growth velocity and a normal IC-GH is poor, whereas marked growth acceleration is noted in children with a low growth velocity and a low 24-hour IC-GH.     

Growth hormone improves clinical status in prepubertal children with cystic fibrosis: results of a randomized controlled trial.

OBJECTIVES: We conducted a 1-year randomized controlled trial to test the hypothesis that growth hormone (GH) improves the clinical status of children with cystic fibrosis. STUDY DESIGN: Nineteen prepubertal children were randomized to control (NonTX, n = 9) or to daily injections of GH (0.3 mg/kg/wk) (GHTX, n = 10) for 1 year. Every 3 months height, weight, and lean tissue mass were measured. Caloric intake, resting energy expenditure, pulmonary function, and respiratory muscle strength were measured every 6 months, as were total number of hospitalizations and courses of outpatient intravenous antibiotics. RESULTS: The GHTX group had significantly greater height, height velocity (NonTX = 3.8 +/- 1.4 cm/y, GHTX = 8.1 +/- 2.4 cm/y; P =.002), weight, weight velocity (NonTX = 2.1 +/- 0.9 kg/y, GHTX = 4.5 +/- 1.1 kg/y; P =.004), and change in lean tissue mass (NonTX = 2.1 +/- 1.6 kg, GHTX = 4.7 +/- 1.7 kg; P =.01) analyzed by the Student t test. The GHTX group had significant improvement in delta forced vital capacity compared with the year before study, and respiratory muscle strength improved. The number of hospitalizations and outpatient intravenous antibiotic courses significantly decreased in the GHTX group but did not change in the NonTX group. No subject had development of cystic fibrosis-related diabetes. CONCLUSIONS: Results of the first randomized controlled trial of GH treatment in cystic fibrosis indicate that GH improves growth and clinical status.     

Predicting and monitoring of growth in children with short stature during the first year of growth hormone treatment.

Fifteen prepubertal short stature children (10 girls, 5 boys), mean age 9.6 years (range 5.2-12.7 years), with normal response to growth hormone stimulation tests (group A) or partial growth hormone deficiency (GHD) of idiopathic nature (group B) were included in a controlled longitudinal study for evaluation of predictive parameters for the long-term growth response after administration of biosynthetic human growth hormone (B-hGH). The average knee-heel length velocity for the first 3 months was significantly correlated to total body height velocity during the following 9 months (p less than 0.0008). By contrast, this association could not be found for height velocity during the same period. The increase in serum values of alkaline phosphatase and insulin-like growth factor I (IGF-1) during the first month of treatment was not significantly correlated to height velocity during the first year. During one year of treatment with B-hGH the mean height velocity for groups A and B increased from 4.4 cm/year (range 2.5-6.5) to 7.6 cm/year (range 4.7-10.6). Bone age advanced by 1.08 +/- 0.60 per chronological year. The ratio between total height and knee-heel length prior to treatment was 3.34 +/- 0.10 and after one year 3.33 +/- 0.10, suggesting a proportional linear growth. An inverse relationship was observed between the ratio and chronological age. In conclusion, early knee-heel measurement may be a useful non-invasive predictor of long-term linear growth in children during treatment with growth hormone, and the ratio of total height to lower leg length may be of importance in detecting dysproportional growth.     

Human growth hormone and gonadotropin releasing hormone analog combination therapy increases predicted height in short normal girls

The "short normal" child constitutes a real challenge for the pediatric endocrinologist. In a subgroup of short normal children, puberty starts at a normal age but with low height, and hence, the final height is expected to be quite compromised. Efforts to improve the outcome in this group have been made in the past with equivocal results. We present the growth data of 8 short girls with normal growth hormone values on provocative testing and low height at puberty initiation. At intervention the height and the stage of puberty were 129.3 +/- 5 cm and II to III, respectively, and the predicted height was 148.8 +/- 2.6 cm. Gonadotropin releasing hormone analog, triptorelin (3.6 +/- 0.5 microg/kg/day) and growth hormone (0.5 IU/kg/week) were used in different sequential order and simultaneously in each child. The mean total treatment period was 47.6 +/- 11.2 months. The mean predicted and the mean final height in the total group were 148.8 +/- 2.6 and 154.5 +/- 3.6 cm, respectively (p:0.028). The final height did not differ from the target height (154.8 +/- 8 cm versus 154.5 +/- 3.6 cm), while in 4 children, the final height was greater than the target height. The height gain (delta Final height - Predicted height) was 5.7 +/- 1.3 cm. If we analyze separately the girls in whom growth hormone was started first and gonadotropin releasing hormone analog followed versus those who started the analog first, the delta Final height - Predicted height was 8 +/- 3 cm in the former and 4.8 +/- 3.1 cm in the latter (p:0.03). It seemed that the difference was accounted for by duration of growth hormone therapy (51.3 +/- 10.6 months versus 28.6 +/- 10.6 months) (p:0.026), rather than by other factors. In conclusion, under the conditions of the present study, the combination of puberty arrest and growth hormone therapy significantly improved predicted height. The most significant determinant of the height gain was the duration of growth hormone therapy.     

Short-term treatment of short stature and subnormal growth rate with human growth hormone

Forty-eight children with short stature, growth rate less than 4 cm/yr, and normal growth hormone response to secretagogues were given exogenous human growth hormone (hGH) for 6 months to determine its effect on the short-term growth rate in these children. All except three had an increase in growth rate with hGH therapy. The mean +/- SD pretreatment growth rate (3.4 +/- 0.8 cm/yr) was significantly less than either the growth rate during 6 months of hGH therapy (6.9 +/- 2.6 cm/yr) or after therapy (4.1 +/- 1.8 cm/yr). Several patterns of response were observed after treatment was stopped: the mean growth rate in 22 children decreased after treatment but remained above basal rates, the mean growth rate in seven children was similar to the rates during treatment, and the mean growth rate in 16 children was less than basal rates. Twenty children received therapy for an additional 6 months and had a mean increase in growth rate from 3.6 +/- 1.3 to 6.7 +/- 2.4 cm/yr. The decreased growth rate after discontinuation of treatment and increased rate with resumption of therapy indicates that maintenance of the increased growth rate might be dependent on continuation of hGH therapy.     

Impaired growth in hyperkinetic children receiving pemoline.

Decreased longitudinal growth was observed in 24 hyperkinetic children receiving pemoline therapy. Mean height velocity was 3.67 +/- 0.25 cm/year during therapy but 5.35 +/- 0.42 cm/year after treatment had been discontinued (P less than 0.01). There appeared to be an inverse relationship between growth velocity and drug dosage. All patients receiving less than the median dose of 3.72 mg/kg grew 4 cm/year or more, while seven of 12 patients receiving more than this dose grew at a slower rate. Body weight, basal and stimulated growth hormone values, and plasma somatomedin concentrations were not significantly altered by pemoline treatment, suggesting that this drug may have a direct effect on cartilage metabolism.