Growth in pre-pubertal children with myelomeningocele (MMC) on growth hormone (GH): the KIGS experience

PURPOSE: To analyse the auxological data of children with myelomeningocele (MMC) on growth hormone (GH) therapy whose growth data was documented within KIGS (Pfizer International Growth Database). Longitudinal growth data of a sub-group of pre-pubertal children were studied after a treatment period of 3 years. PATIENTS AND METHODS: Eighty patients (38 m, 42 f) with MMC with a median chronological age (CA) of 11.6 years (at latest visit) on GH were registered in the KIGS database. In 52 patients, GH deficiency was documented. GH therapy started with a median dose of 0.23 mg kg(-1) per week. The 3-year longitudinal growth was analysed in 21 patients (13 m, 8 f; median CA 9.2 years, latest visit), all of whom were pre-pubertal at start and during GH therapy. RESULTS: GH therapy started at 7.5 years with a dose of 0.23 mg kg(-1) per week. Birth length SDS (-0.51) and mid-parental height SDS (+0.07) were in the normal range. BMI SDS at start was +0.24, at latest visit -0.03. After a median treatment duration of 3.0 years (latest visit), height SDS improved from -2.97 (start of GH) to -2.01. The sub-group of pre-pubertal MMC patients started GH therapy (dose 0.22 mg kg(-1) per week) at 6.2 years. Growth velocity (GV) SDS increased significantly (at start: -1.77; 1 year: +2.60, 2 years: +2.25, 3 years: +1.24), thus height SDS improved from -3.25 at start to -1.87 at 36 months. BMI SDS was in the normal range and remained unchanged during GH therapy. No major side effects of GH were recorded. CONCLUSION: GH had positive effects on height SDS in MMC patients. The analysis of the longitudinal growth data of pre-pubertal MMC patients showed a significant increase in GV SDS and improvement of height SDS.     

Growth hormone treatment in short children with beta-thalassemia major

The effect of one year recombinant human growth hormone (rhGH) treatment on growth rate and bone age was studied in ten short prepubertal children with beta-thalassemia major (age range 7.10-12.03 yr) with normal GH response to provocative stimuli. rhGH was given subcutaneously every day in a dose of 28 IU/m2/week. In the 10 children who completed 12 months of treatment the growth velocity increased from 4.22+/-0.81 cm/yr (-1.38+/-0.80 SDS for CA) to 7.61+/-1.16 cm/yr (+2.27+/-1.64 SDS for CA). IGF-I was low before treatment, 138.3 +/-38.9 ng/ml, and rose significantly to 232.2+/-122.1, 243.2+/-98.4 and 227.5+/-86.2 at 3, 6 and 12 months post-treatment, respectively (p<0.01). Bone maturation was accelerated in proportion to the increase in chronological age. The mean pre-treatment bone age in the ten children was 8.20+/-1.97 and increased to 9.55+/-1.80 yr after one year of treatment. Our data demonstrate that GH treatment of thalassemic children with normal GH reserve and low serum IGF-I concentrations with supraphysiological doses of rhGH for one year can cause a significant increase in serum IGF-I levels and growth velocity, but it remains to be elucidated whether long-term administration will affect the final height.     

Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis

Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 ± 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone (Gn-RH) analogue treatment (D-Trp⁶-LH-RH, 60 μg/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values (< 3.6μg/l) 33.3%), stimulated levodopa GH peaks (pathological values (<10.0 μg/I) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 ± 0.9 cm/year; 6 months 6.4 ± 1.9cm/year, p < 0.001 versus baseline; 12 months 6.0 ± 1.3cm/year, p < 0.001 versus baseline). There was a significant increase in height SDS for bone age (baseline –1.6 ±0.5 SDS; 12 months -1.04 ± 0.6SDS; p < 0.002) and in predicted adult height (baseline 152.0 ± 3.6cm; 12 months 155.9 ± 3.4cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.     

Chronic growth retardation with normal growth hormone response to provocative stimuli and low somatomedin activity. Long-term therapy with human growth hormone

Four prepubertal children with chronic growth retardation (growth velocities less than or equal to 4 cm/yr), normal growth hormone (GH) response to provocative stimuli and low basal but increased somatomedin activity values after GH administration, received continuous GH-therapy (4 IU/three times a week) for an 18-24-month period. Growth velocity doubled during the first 12 months of therapy and remained 4-6 cm/yr until the end. Bone age progressed according to chronological age and adult height predictions improved. No thyroid function or carbohydrate and lipid metabolism anomalies were observed. After completion of this GH-therapy period, patients remained off treatment during the following six months. Growth velocities were similar to pre-GH-treatment values in two patients, lower in the third and higher in the fourth, who was by then pubertal. Thus, in these patients, long-term GH-therapy promoted growth and improved adult height prediction.     

Auxological and endocrinological evaluation of children with hydrocephalus and /or meningomyelocele

Short stature and precocious puberty are frequently found in children with hydrocephalus and/or meningomyelocele (MMC). However, aetiology and pathophysiology have not been well characterized. In this study, 108 patients aged between 3 and 17.8 years were evaluated. Growth was documented on the basis of arm span measurements. Short arm span was found in 47 (43.5%) children with hydrocephalus and/or MMC. Mean arm span was −2.0 standard deviation score (SDS) (−6.4 to +0.8) in 43 girls and −1.4 SDS (−5.6 to +1.3) in 65 boys. When growth deficiency (more than −2.0 SDS) was diagnosed by arm span measurement (24 F, 23 M) or when early sexual maturation was found (6 F, 9 M), endocrine evaluation followed. Levels of serum insulin-like growth factor and insulin-like growth factor binding protein-3 were low in 22 of 62 (33.8%) patients. In 9 of 62 (14.5%) patients, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were found to be increased. Growth hormone (GH) deficiency was diagnosed by means of two different stimulation tests (clonidine and arginine) in 7 of 62 (11.3%) patients. In another 3 of 62 (4.8%) children, 12 h night time GH sampling showed low maximum peak levels and decreased area under the curve values, suggesting neurosecretory GH dysfunction. Precocious puberty or early onset of puberty associated with elevated luteinising hormone and follicle stimulating hormone concentrations after stimulation with luteinising hormone releasing hormone was found in 13 of 108 (12.0%) patients (age 7–9 years). Free thyroxine was abnormally low in 2 of 62 (3.2%) patients. Cortisol was within the normal range in all 62 (100%) tested patients. Conclusions Short arm span in children with hydrocephalus and/or MMC is frequently accompanied by GH deficiency or neurosecretory GH dysfunction. Early onset of puberty is another frequent finding. Both hormonal disorders may be the consequence of damage to the hypothalamus or the pituitary gland caused by increased intracerebral pressure or increased mass of cerebrospinal fluid. Received: 31 May 1996 / Accepted: 21 October 1996     

Growth hormone and segmental growth in survivors of head and neck embryonal rhabdomyosarcoma.

AIMS: To assess the impact of treatment for embryonal rhabdomyosarcoma on spinal growth and limb length and examine the response of these parameters to growth hormone (GH) treatment. METHODS: We conducted a retrospective case note review of 17 survivors of head and neck rhabdomyosarcoma followed up at a single institution. All children had been treated with chemotherapy and local radiotherapy. Growth velocity, height, sitting height, and subischial limb length SDS scores were analysed. RESULTS: Growth failure secondary to isolated GH deficiency (GHD) developed in 7/17 patients. GHD occurred at a median (range) of 3.4 (1.3-9.9) years after radiotherapy tumour doses of 46 (40-50) Gy. Growth velocity, height, and subischial limb length SDS were significantly reduced in the GHD group and improved with GH therapy. CONCLUSIONS: GH treatment resulted in a significant improvement in sitting height SDS. We discuss the unexpected improvement in spinal growth in survivors with GHD.     

Insulin-like growth factor-I treatment in two children with growth hormone gene deletions.

Two unrelated Brazilian patients had homozygous 6.7 kb deletions in the GH-1 gene (girl and boy, 1.8 and 3.3 yr, heights -7.9 and -6.0 SDS, respectively). Desensitization using small amounts of exogenous GH (0.033 IU/kg body weight/week, divided into daily s.c. injections) was attempted, but anti-GH antibodies appeared. Replacement with usual doses of hGH induced only transient increase in growth. IGF-I therapy with increasing doses resulted in catch-up growth without side-effects. Growth velocity was 7.5 cm/yr in the first year and 8.4 cm/yr in the next 6 months in patient 1, and 6.7 cm/yr in the first year, 5.9 cm/yr in the second year and 7.9 cm/yr in the third year of IGF-I treatment in patient 2, when the daily dose of 240 micrograms/kg was divided into three injections. IGFBP-3 levels were low (0.55 and 0.40 mg/I) and did not increase after IGF-I treatment, suggesting that this GH effect is not mediated by IGF-I, and injected IGF-I had a rapid disappearance rate. We conclude that IGF-I promotes growth by endocrine mechanisms and constitutes an effective treatment for patients with GH insensitivity secondary to GH antibodies.     

Enhancement of linear growth and weight gain by cyproheptadine in children with hypopituitarism receiving growth hormone therapy

Cyproheptadine (Cp), an antihistamine serotonin antagonist drug with appetite-stimulating activity, was given to children with growth hormone (GH) deficiency to test the hypothesis that increased weight gain would enhance the effect of GH on linear growth. Six patients with idiopathic GH deficiency received GH 0.08 U/kg three times per week plus Cp 0.25 to 0.4 mg/kg/day for 4-month periods, alternating with 4-month periods of GH plus placebo, on average for 16 months. Overall, height velocity (HV) increased from 9.1 +/- 2.4 with GH alone to 12.1 +/- 2.1 cm/yr with GH-Cp (P = 0.01) and weight velocity (WV) increased substantially from 1.3 +/- 1.3 to 7.8 +/- 3.6 kg/yr (P = 0.01). For 10 of 11 8-month treatment intervals completed, HV was greater during GH-Cp treatment than during GH alone, and there was a good correlation between HV and WV for each 4-month observation period (r = 0.64, P less than 0.002). These findings should be considered preliminary because of the small number of patients, but suggest that weight gain induced by cyproheptadine results in improved linear growth in patients given GH and that this drug may be useful in optimizing the response to GH therapy.     

Growth hormone and segmental growth in survivors of head and neck embryonal rhabdomyosarcoma

AIMS—To assess the impact of treatment for embryonal rhabdomyosarcoma on spinal growth and limb length and examine the response of these parameters to growth hormone (GH) treatment.
METHODS—We conducted a retrospective case note review of 17 survivors of head and neck rhabdomyosarcoma followed up at a single institution. All children had been treated with chemotherapy and local radiotherapy. Growth velocity, height, sitting height, and subischial limb length SDS scores were analysed.
RESULTS—Growth failure secondary to isolated GH deficiency (GHD) developed in 7/17 patients. GHD occurred at a median (range) of 3.4(1.3-9.9) years after radiotherapy tumour doses of 46 (40-50) Gy. Growth velocity, height, and subischial limb length SDS were significantly reduced in the GHD group and improved with GH therapy.
CONCLUSIONS—GH treatment resulted in a significant improvement in sitting height SDS. We discuss the unexpected improvement in spinal growth in survivors with GHD.

     

Height prognosis of children with true precocious puberty and growth hormone deficiency: effect of combination therapy with gonadotropin releasing hormone agonist and growth hormone.

We evaluated height prognosis and therapeutic efficacy of long-term, combination therapy with gonadotropin releasing-hormone agonist and growth hormone (GH) in five children (three girls) with coexistent precocious puberty and GH deficiency. Their clinical characteristics and growth response were compared with those of 12 girls with idiopathic true precocious puberty and eight prepubertal GH-deficient children (one girl). Precocious GH-deficient subjects were older than the precocious GH-sufficient children (9.5 +/- 1.8 years vs 6.5 +/- 1.3 years; mean +/- SD), but bone ages were comparable (12 +/- 3.7 years vs 10 +/- 0.9 years); their chronologic age was similar to that of the prepubertal GH-deficient children (9.6 +/- 2.1 years), but bone age was significantly more advanced (6.9 +/- 2.3 years). The mean height velocity of the prepubertal GH-deficient children (3.8 +/- 1.5 cm/yr) was lower than that of the precocious GH-deficient subjects (6.7 +/- 1.6 cm/yr) and the precocious GH-sufficient children (9.5 +/- 2.9 cm/yr). Baseline adult height prediction z scores were significantly lower in the precocious GH-deficient children (-3.7 +/- 1.0) than in either the precocious GH-sufficient children (-2.2 +/- 1.0) or the prepubertal GH-deficient subjects (-1.5 +/- 0.8). During therapy with gonadotropin releasing-hormone agonist, growth rates slowed to an average of 3.7 cm/yr in the precocious GH-deficient children but increased after the addition of GH to 7.4 cm during the first year of combination therapy. After 2 to 3 years of combination therapy, height predictions increased an average of 10 cm, compared with an increase of 2.8 cm in the precocious GH-sufficient group treated with gonadotropin releasing-hormone agonist alone. We conclude that combination treatment with gonadotropin releasing-hormone agonist and GH improves the height prognosis of children with coexistent true precocious puberty and GH deficiency, but falls short of achieving normal adult height potential.     

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.     

Biosynthetic growth hormone therapy in children with growth hormone deficiency: Experience at AIIMS,New Delhi

A total of 20 previously untreated children with growth hormone deficiency (GHD) were treated for one year with biosynthetic human growth hormone (hGH). The mean chronologic age was 9.43±3.52 years with a height age of 5.02 years, and bone age 9.43±3.52 (TW2-RUS) 6.42 years. The mean pretreatment growth velocity was 2.43±0.90 cm/year. Of these 14 children had complete GHD (peak GH levels less than 5 ng/ml) and 6 had partial GHD. They were treated with recombinant GH in a dose of 0.5 IU/kg/week divided into 6–7 injections per week subcutaneously at night. The mean growth velocity increased to 8.88±2.10 cm/yr at the end of 6 months and 8.00±2.21 cm/yr at 12 months. The actual gain ranged from 6–11 cm in a year. There were no local adverse reactions. One child developed vitiligo of the face and another transient hyperglycemia.     

Growth hormone treatment in 35 prepubertal children with achondroplasia: a five-year dose-response trial

BACKGROUND: Achondroplasia is a skeletal dysplasia with extreme, disproportionate, short stature. AIM: In a 5-y growth hormone (GH) treatment study including 1 y without treatment, we investigated growth and body proportion response in 35 children with achondroplasia. METHODS: Patients were randomized to either 0.1 IU/kg (n = 18) or 0.2 IU/kg (n = 17) per day. GH treatment was interrupted for 12 mo after 2 y of treatment in prepubertal patients to study catch-down growth. Mean height SDS (HSDS) at start was -5.6 and -5.2 for the low- and high-dose groups, respectively, and mean age 7.3 and 6.6 y. RESULTS: Mean growth velocity (baseline 4.5/4.6 cm/y for the groups) increased significantly by 1.9/3.6 cm/y during the first year and by 0.5/1.5 cm/y during the second year. During the third year, a decrease of growth velocity was observed at 1.9/1.3 cm/y below baseline values. HSDS increased significantly by 0.6/0.8 during the first year of treatment and in total by 1.3/1.6 during the 5 y of study. Sitting height SDS improved significantly from -2.1/-1.7 to -0.8/0.2 during the study. Body proportion (sitting height/total height) or arm span did not show any significant change. CONCLUSION: GH treatment of children with achondroplasia improves height during 4 y of therapy without adverse effect on trunk-leg disproportion. The short-term effect is comparable to that reported in Turner and Noonan syndrome and in idiopathic short stature.     

Noonan's syndrome: abnormalities of the growth hormone/IGF-I axis and the response to treatment with human biosynthetic growth hormone

Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5-12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.     

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.     

Treatment to near adult stature of patients with myelomeningocele with recombinant human growth hormone

We evaluated near adult statural outcome of treating growth hormone (GH) deficient children (peak GH values <10 ng/ml) with myelomeningocele (MMC) with 0.3 mg/kg/week of recombinant human GH. Retrospective evaluation of 20 patients (12 males) who were consistently measured using recumbent length and who had achieved more than 90% of their adult stature on GH treatment were included. Pretreatment scoliosis was present in 13 patients (<30 degrees); 16 patients had lumbar level of lesion, while four had sacral level of lesion; 19 of 20 had a ventriculoperitoneal shunt. During GH treatment, two girls were successfully treated with leuprolide acetate for precocious puberty, two patients were concurrently treated for hypothyroidism and were euthyroid. Standard deviation score (SDS) for recumbent length at near adult stature increased in comparison to the general adult population and untreated adults with MMC (-2.6 to -1.4 and +0.6, respectively, p <0.001). Fifteen of 20 patients at near adult stature were above the 3rd percentile of current United States growth charts. These patients were less overweight as body mass index (BMI) was less than untreated shorter adults with MMC (p <0.01 for females, <0.001 for males). Scoliosis did not progress. Conclusion: Near adult stature for GH-treated children with MMC is significantly greater than untreated adults with MMC. Relative obesity is decreased with significant improvement of BMI. This is the first report of statural outcome near completion of growth for GH-treated children with MMC.     

Growth hormone testing in short children and their response to growth hormone therapy

Because current concepts of growth hormone (GH) testing and GH treatment have become controversial, we investigated the GH secretory patterns in children with normal and short stature. Twenty-four-hour serum GH levels were evaluated in three groups of children. Group 1 was composed of children with normal height (mean height = 0.02 SD, n = 33); group 2 was composed of short children (less than 5th percentile, n = 63) with normal results on provocative GH testing; and group 3 was composed of short children (less than 5th percentile, n = 7) with subnormal results on provocative GH testing. Mean +/- SD (range) GH levels during 24-hour studies of GH secretion were 1.6 +/- 1.1 (0.5 to 5.6), 1.8 +/- 1.2 (0.6 to 6.3), and 0.9 +/- 0.4 (0.5 to 1.7) ng/ml in groups 1, 2, and 3, respectively. No statistical difference existed in mean GH levels between groups 1 and 2 or between groups 1 and 3. The mean GH concentration from 24-hour studies in group 2 children did not correlate with chronologic age, height standard deviation, growth rates, or insulin-like growth factor 1 levels. The linear growth rate of 26 of 28 children in group 2 who received GH therapy for 6 months improved by 2 cm/yr or more; the mean +/- SD growth rate was 4.0 +/- 1.3 and 8.8 +/- 2.0 cm/yr during control and treatment periods, respectively, for these 28 children. Mean GH levels from testing did not predict response to GH during 6 months of therapy. Children with slower growth rates responded better to GH therapy (p less than 0.05). We conclude that (1) in 24-hour studies, GH levels in normal children overlapped with those of short children, including those with classic GH deficiency, (2) in 24-hour studies, GH levels did not predict responses of linear growth to short-term GH treatment, nor did they correlate with children's heights or growth velocities, and (3) the majority of short children in group 2 treated with GH for 6 months had an increase in linear growth velocity, the mean +/- SD change being 4.8 +/- 2.0 cm/yr.     

Predictors of first-year growth response to a fixed-dose growth hormone treatment in children born small for gestational age: results of an open-label, multicenter trial in the United States

BACKGROUND: Previous studies of varied populations of non-uniformly defined children born small for gestational age (SGA) receiving different growth hormone (GH) regimens have found that GH treatment increased growth velocity and adult height and was safe. The GH dose was the major predictor of first year growth response. AIM: To identify pre- and within-treatment predictors of growth in well defined children born SGA treated with a fixed dose of GH. METHODS: 139 short, prepubertal children born SGA (i.e. birth weight and/or length > or =2 standard deviations below the mean) received Genotropin (rhGH) at 0.24 mg/kg/wk for 1 month then an additional 11 months at a dose of 0.48 mg/kg/wk, the FDA-approved dose of GH for children born SGA. RESULTS: Height improved significantly by month 3, with progressive improvement over the entire 12 months (median height SDS change of 0.78). Pretreatment predictors of growth included baseline bone age, IGFBP-3, total cholesterol, WBC and height SDS minus mid-parental height SDS. Within-treatment predictors of the change (Delta) height SDS at month 12 were the A height SDS at months 3 and 6 and growth velocity SDS at months 3 and 6. CONCLUSION: GH at 0.48 mg/kg/wk was well tolerated and improved growth in children born SGA; the Delta IGF-I was not predictive of the 12 month height SDS gain, while the Delta height SDS at 3 and 6 months were predictive. Underweight children grew as well as normal weight children, and both groups showed improved body composition following GH treatment.     

Methionyl human growth hormone and oxandrolone in Turner syndrome: preliminary results of a prospective randomized trial

Seventy girls with Turner syndrome, 4 to 12 years of age, were randomly assigned to receive either no treatment (control) or methionyl human growth hormone (0.125 mg/kg three times per week), oxandrolone (0.125 mg/kg/day), or combination hGH plus oxandrolone therapy. Baseline growth rates averaged 4.3 cm/yr, and all were within 2 SD of mean growth velocity for age in girls with Turner syndrome. Sixty-seven girls remained in the study for a minimum of 1 year. Growth rates and growth velocity (in standard deviations for age in girls with Turner syndrome) were control 3.8 cm/yr (-0.1 SD), hGH 6.6 cm/yr (+2.3 SD), oxandrolone 7.9 cm/yr (+3.7 SD), and combination therapy 9.8 cm/yr (+5.4 SD). Mean bone ages advanced 1.0 years (hGH), 1.3 years (oxandrolone), and 1.6 years (combination). However, median increments in height age/bone age (delta HA/delta BA) ratios ranged from 1.0 to 1.1 for treatment groups, compared with 0.8 for the controls. Predicted adult height by the method of Bayley-Pinneau increased 2.5 cm for hGH or oxandrolone alone, and 3.2 cm for combination treatment. These data indicate that both hGH and oxandrolone can significantly stimulate short-term skeletal growth in patients with Turner syndrome, and potentially increase final adult height.     

Growth hormone treatment in young children with Down's syndrome: effects on growth and psychomotor development.

BACKGROUND: Learning disability and short stature are cardinal signs of Down's syndrome. Insulin-like growth factor I (IGF-I), regulated by growth hormone (GH) from about 6 months of age, may be involved in brain development. AIMS: To study long term effects of GH on linear growth and psychomotor development in young children with Down's syndrome. Study design-Fifteen children with Down's syndrome were treated with GH for three years from the age of 6 to 9 months (mean, 7.4). Linear growth, psychomotor development, skeletal maturation, serum concentrations of IGF-I and its binding proteins (BPs), and cerebrospinal fluid (CSF) concentrations of IGF-II were studied. RESULTS: The mean height of the study group increased from -1.8 to -0.8 SDS (Swedish standard) during treatment, whereas that of a Down's syndrome control group fell from -1.7 to -2.2 SDS. Growth velocity declined after treatment stopped. Head growth did not accelerate during treatment. No significant difference in mental or gross motor development was found. The low concentrations of serum IGF-I and IGFBP-3 became normal during GH treatment. CONCLUSIONS: GH treatment results in normal growth velocity in Down's syndrome but does not affect head circumference or mental or gross motor development. Growth velocity declines after treatment stops.