Two-Year Results of Treatment with Methionyl Human Growth Hormone in Children with Turner Syndrome

ABSTRACT. Methionyl growth hormone (somatrem) in a daily dosage of 4 IU/m² body surface area was administered to 16 girls with Turner syndrome. Low dose ethinyl estradiol (0.1 μg/kg body weight) was added in girls aged 13 years or more. Mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) and 5.3 (1.3) cm/year in the first and second year, respectively. Bone age advanced 1.8 years over 2 years and predicted adult height was increased. Apart from the occurrence of anti-GH antibodies there were no side effects. In conclusion, somatrem is an efficacious and safe therapy for short stature in Turner syndrome over a period of 2 years. Longer follow-up is needed before conclusions about its effect on final height can be drawn.     

Growth hormone treatment regimens in girls with Turner syndrome. Dutch Advisory Group on Growth Hormone

To optimize growth hormone (GH) treatment in girls with Turner syndrome, two multicentre studies were carried out in The Netherlands: a frequency-response study (study 1) and a dose-response study (study 2). In study 1, 19 girls with Turner syndrome, aged 11 years or older, were treated with one or two daily injections of GH at a total dose of 6 IU/m2/day (0.067 mg/kg/day) and ethinyloestradiol given orally at a dose of 0.05 microg/kg/day. All the girls reached final height. The mean (+/-SD) gain in final height was not significantly different between the once- or twice-daily regimens (7.6 +/- 2.3 versus 5.1 +/- 3.2 cm, respectively). The mean final height attained was 155.5 +/- 5.4 cm. All the girls exceeded their adult height prediction. In study 2, 68 girls with Turner syndrome, aged 2-11 years, were randomized into three dosage groups: A, B and C. During the first year, the girls in all the groups received GH at a dose of 4 IU/m2/day (0.045 mg/kg/day), which group A continued to receive throughout the study. At the start of the second year, groups B and C were switched to a dose of 6 IU/m2/day, which the girls in group B continued to receive for the remainder of the study. At the start of the third year, the girls in group C were switched to a dose of 8 IU/m2/day (0.090 mg/kg/day) for the remainder of the study. After 7 years of GH treatment, height SDS (based on Turner syndrome and normal population references) increased significantly in all three groups, but significantly more in groups B and C compared with group A (p = 0.02 and p = 0.001, respectively). Predicted adult height increased significantly, without a significant difference between the three dosage groups. The mean final heights of 25 of the girls were 159.1, 161.8 and 162.7 cm for groups A, B and C, respectively.     

Physical effects of growth hormone treatment in children with Prader-Willi syndrome

A randomized, controlled study of 54 children (age, 4-16 years) with Prader-Willi syndrome was conducted to assess the potential beneficial effects of growth hormone (GH) treatment. After observation for 6 months, the children were randomized to receive GH at a dose of 3 IU/m²/day (1 mg/m²/day) ( n = 35) or no intervention ( n = 19). The effects of GH treatment on linear growth, body composition, muscle strength, pulmonary function and resting energy expenditure were assessed. The levels of GH secreted in resonse to clonidine stimulation were universally low, and mean (± SD) insulin-like growth factor I SDS was -1.2 ± 0.8 pretreatment. In children treated for 1 year, mean height velocity SDS significantly increased from -1.0 ± 2.5 to 4.6 ± 2.9 ( p < 0.0001), mean percentage body fat decreased from 46.3 ± 8.4% to 38.4 ± 10.7% ( p < 0.001), mean lean body mass increased from 20.5 ± 6.3 kg to 25.6 ± 4.3 kg ( p <0.01) and respiratory muscle function and physical strength imporved. Mean respiratory quotients significantly decreased from 0.81 to 0.77 ( p < 0.001); however, resting energy expenditure did not change. Therefore, GH therapy appears to reduce some of the physical disabilities experienced by children with Prader-Willi syndrome.     

Management of Growth Hormone Deficiency Through Puberty

ABSTRACT. As a model of the growth hormone (GH) dependence of growth in prepuberty and puberty, the growth of 182 children (93 boys, 89 girls) who survived in first remission for treatment of acute lymphoblastic leukaemia was examined. Chemotherapy regimens, including intrathecal methotrexate, were similar in all patients, but CNS treatment differed, in that one group received 2400 cGy cranial irradiation, while the other received 1800 cGy. There was a significant decrease in height SDS during prepuberty, which was equivalent in both sexes, whereas there was a much greater decrease in pubertal growth in girls than in boys. Girls treated with the lower dose regimen of cranial irradiation had their onset of pubertal maturation significantly advanced, to a mean of 9.9 years ( p < 0.001). Previous studies have indicated that the duration of puberty is shortened by GH treatment in patients with idiopathic multiple pituitary hormone deficiency or isolated GH deficiency (GHD). To determine whether an increase in the dose of GH administered during the adolescent growth spurt would improve final height, a prospective randomized trial was performed in 32 children (25 boys, 7 girls) with isolated GHD treated with a GH dose regimen of 15 IU/m²/week as daily s.c. injections. At the onset of the pubertal growth spurt, the patients were randomized either to an unchanged dose or to 30 IU/m²/week. There was no significant change in height velocity with the doubled dose of GH, but there was a trend in the advancement of pubertal maturation which was considered to be dose related. It is suggested that these findings are of relevance to the treatment of GHD in puberty, especially in girls with early or precocious puberty occurring as a consequence of low-dose cranial irradiation. It is concluded that optimum final heights may not be achieved in these patients without the therapeutic manipulation of the onset and/or duration of puberty.     

Physiological Growth Hormone Secretion and Response to Growth Hormone Treatment in Children with Short Stature and Intrauterine Growth Retardation

Stanhope, R., Ackland, F., Hamill, G., Clayton, J., Jones, J. and Preece, M.A. (Department of Growth and Development, Institute of Child Health, London and Serono Laboratories, UK). Physiological growth hormone secretion and response to growth hormone treatment in children with short stature and intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 47, 1989.
Physiological growth hormone (GH) secretion was examined in 31 children (8 girls, 23 boys) with short stature secondary to intrauterine growth retardation (IUGR). Seventeen (4 girls, 13 boys) had dysmorphic features of Russell-Silver syndrome. Four of the 31 children had GH insufficiency with peak GH levels of < 20 mU/I during the night. Nine of the patients (8 of whom had Russell-Silver syndrome) had a single nocturnal GH pulse. Twenty-three children (6 girls, 17 boys) were randomized into two groups treated with either 15 or 30 U/m²/week of GH by daily subcutaneous injections. Age, sex distribution, pretreatment height velocity SD score (SDS), and distribution of dysmorphic and non-dysmorphic children were similar in both groups. The group treated with 15 U/m2/week for a mean of 0.82 years showed an increase in mean height velocity SDS from - 0.61 to +1.09, and the group treated with 30 U/m²/week for a mean of 0.92 years showed an increase in mean height velocity SDS from -0.69 to +3.48. The results suggest that physiological GH insufficiency is probably common in children with Russell-Silver syndrome and that both dysmorphic and non-dysmorphic children with short stature secondary to IUGR will respond to GH treatment. Initial evidence suggests that the increase in short-term growth velocity does not result in an improved final height prognosis.     

Synchronization of Growth Hormone Therapy

Based on the hypothesis of periodical refractoriness of the growing tissue to exogenous administration of GH, an experimental approach is presented in which the dosage of GH was adjusted to the natural occurrence of periodical changes of the lower leg growth velocity in five children with short stature. Two 6-month periods were compared, during which the children received an identical cumulative dose of GH of 224 IU/m². During the first period, the children received a constant GH dose of 14 IU/m²/week by daily subcutaneous injection, whereas a low/high dose alternation was administered at approximately 3-week intervals synchronously with the occurrence of mini growth spurts during the second 6-month period. In all the children, mean linear growth of the lower leg accelerated during the period of synchronization by 595% compared to the previous growth rate during constant GH administration.     

Treatment of children with congenital heart disease and growth retardation with recombinant human growth hormone

Seven prepubertal short children with congenital heart disease were treated with recombinant human growth hormone (GH). Although complete surgical correction was performed for their heart disease at least 2 years before the start of GH therapy, improvement in growth was less than expected in these children. They received 0.5 IU kg⁻¹ week⁻¹ of GH daily for 2 years or more. The growth rate increased from a mean of 4.3 cm year⁻¹ before treatment to a mean of 7.8 cm year⁻¹ in the first year and to a mean of 6.3 cm year⁻¹ in the second year of treatment. Their mean standardized height improved from −3.41 ± 0.78 to −2.54 ± 0.62 after 2 years. The mean height age difference minus the bone age difference became positive in these children. We conclude that recombinant GH increases the growth rate in children with congenital heart disease and prepubertal growth retardation.     

Growth hormone treatment of Turner syndrome patients with insufficient growth hormone response to pharmacological stimulation tests

Growth before and during treatment with biosynthetic human growth hormone (hGH) was studied in 13 patients with Turner syndrome (TS) and a growth hormone (GH) response of less than 10 g/l to two standard provocative tests. During 1 year of treatment with hGH (0.15 IU/kg per day) height velocity (mean±SD) increased significantly (P<0.001) from 3.7±1.8 cm/year to 7.6±1.5 cm/year. The auxological data in these girls before and during treatment with hGH were similar to those observed in TS patients with a normal response of GH to pharmacological stimuli. It is concluded that in girls with Turner syndrome GH testing should only be performed when height velocity is below the Turner norm. In TS patients with residual growth potential a clinically significant growth acceleration can be obtained with a higher-than-replacement dose of hGH, i.e. 0.15 IU/kg per day, regardless of GH testing.     

A decade of growth hormone treatment in girls with Turner syndrome in the UK. UK KIGS Executive Group.

Fifteen per cent of children treated with growth hormone (GH) are receiving treatment for Turner syndrome, but few results are available on final height in the UK. In this study, data were obtained from the UK KIGS database for 485 girls with Turner syndrome who were treated from 1986, allowing an audit of practice and outcome over 10 years. Over the decade, the mean age of starting growth hormone treatment fell from 10.4 to 8.5 years and the starting dose increased from 0.55 to 0.95 IU/kg/week. The frequency of injections increased from three to six or seven/week. Some girls received suboptimal doses, which also differed depending on whether they were based on weight or surface area. To assess what height gain might be expected at final height, all 52 girls who were prepubertal at the start of treatment, which continued for four years or more, and who had reached final height or had a growth velocity < 2 cm/year were selected. Their mean gain in final height was 5.2 cm and the GH dose was 0.78 IU/kg/week over 5.8 years. Final height gain correlated significantly with duration of treatment, total dose received, and first year response, which itself related to starting dose. This audit shows a changing pattern of treatment over the past decade, which in many instances has been inadequate. When treatment starts before puberty and continues through to final height, with a dose of 30 IU/m2/week in six or seven injections, a mean increase in final height of 5 cm or more would be expected.     

Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation

A total of 130 short children were included in a French multicentre study and randomized between a control group (group A) and two groups treated with daily subcutaneous injections of GH at doses of 0.7 IU/kg/week (group B) and 1.4 IU/kg/week (group C) for 2 years. Height velocity was significantly increased ( p <0.0005) in groups B and C, with a greater increase in group C than in group B ( p < 0.001). The benefit after 2 years compared with controls was 4.3 cm in group B and 5.9 cm in group C. The rate of bone maturation was not affected by GH therapy. These results led to the conclusion that 2 years of treatment with GH improves final height prognosis in children with short stature secondary to IUGR, and that this effect is dose dependent. The effect on final height has still to be demonstrated.     

Final height in girls with Turner's syndrome treated with once or twice daily growth hormone injections. Dutch Advisory Group on Growth Hormone.

OBJECTIVES: To study final height in girls with Turner's syndrome treated with once or twice daily injections of growth hormone (GH) in combination with low dose ethinyl oestradiol. DESIGN: Until final height was reached, the effect of fractionated subcutaneous injections given twice daily was compared with once daily injections of a total GH dose of 6 IU/m2/day. Twice daily injections were given as one third in the morning and two thirds at bedtime. All girls concurrently received low dose oestradiol (0.05 microgram ethinyl oestradiol/kg/day, increased to 0.10 microgram/kg/day after 2.25 years). PATIENTS: Nineteen girls with Turner's syndrome aged > or = 11 years (mean (SD) 13.6 (1.7) years). MEASUREMENTS: To determine final height gain, we assessed the difference between the attained final height and the final height predictions at the start of treatment. These final height predictions were calculated using the Bayley-Pinneau (BP) prediction method, the modified projected adult height (mPAH), the modified index of potential height (mIPHRUS), and the Turner's specific prediction method (PTSRUS). RESULTS: The gain in final height (mean (SD)) was not significantly different between the once daily and the twice daily regimens (7.6 (2.3) v 5.1 (3.2) cm). All girls exceeded their adult height prediction (range, 1.6-12.3 cm). Thirteen of the 19 girls had a final height gain > 5.0 cm. Mean (SD) attained final height was 155.5 (5.4) cm. A "younger bone age" at baseline and a higher increase in height standard deviation score for chronological age (Dutch-Swedish-Danish references) in the first year of GH treatment predicted a higher final height gain after GH treatment. CONCLUSIONS: Division of the total daily GH dose (6 IU/m2/day) into two thirds in the evening and one third in the morning is not advantageous over the once daily GH regimen with respect to final height gain. Treatment with a GH dose of 6 IU/m2/day in combination with low dose oestrogens can result in a significant increase in adult height in girls with Turner's syndrome, even if they start GH treatment at a relatively late age.     

A decade of growth hormone treatment in girls with Turner syndrome in the UK

Fifteen per cent of children treated with growth hormone (GH) are receiving treatment for Turner syndrome, but few results are available on final height in the UK. In this study, data were obtained from the UK KIGS database for 485 girls with Turner syndrome who were treated from 1986, allowing an audit of practice and outcome over 10 years. Over the decade, the mean age of starting growth hormone treatment fell from 10.4 to 8.5 years and the starting dose increased from 0.55 to 0.95 IU/kg/week. The frequency of injections increased from three to six or seven/week. Some girls received suboptimal doses, which also differed depending on whether they were based on weight or surface area. To assess what height gain might be expected at final height, all 52 girls who were prepubertal at the start of treatment, which continued for four years or more, and who had reached final height or had a growth velocity < 2 cm/year were selected. Their mean gain in final height was 5.2 cm and the GH dose was 0.78 IU/kg/week over 5.8 years. Final height gain correlated significantly with duration of treatment, total dose received, and first year response, which itself related to starting dose. This audit shows a changing pattern of treatment over the past decade, which in many instances has been inadequate. When treatment starts before puberty and continues through to final height, with a dose of 30 IU/m²/week in six or seven injections, a mean increase in final height of 5 cm or more would be expected.

     

Preliminary validation of a prediction model for the short-term growth response to growth hormone therapy in children with idiopathic short stature

A discriminant scoring system, using multivariate analysis, has been developed for pretreatment prediction of responsiveness to a 6-month trial of growth hormone (GH) treatment in short children with subnormal growth velocity, but without GH deficiency. Inclusion criteria included a birth weight above 2.5 kg, height below the 3rd centile for chronological age, height velocity below the 25th centile for bone age, no signs of puberty, a maximal GH response to pharmacological stimulation of above 10 μg/l and treatment with GH at a dose of 12–16 IU/m²/week. Children with an increase in height velocity greater than 2.5 cm/year after therapy were considered to be responders. Pretreatment clinical data from 67 patients were employed in a discriminant analysis in order to establish the model. The scoring system developed was as follows: score = -0.4 + 0.92X₁– 0.87X₂, where X₁ is the height velocity SD score (SDS) for chronological age, and X₂ is the bone age SDS for chronological age. This model had a specificity of 96.3% and a sensitivity of 92.5% in predicting the responsiveness to GH. The model has subsequently been applied to a group of 14 patients in order to establish its validity; in this group its sensitivity was 83.3% and its specificity 100%. These preliminary data suggest that the model can be used as a guideline for selecting short, slowly growing, non-GH-deficient children who will respond to short-term GH therapy.     

Benefits of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in pediatric renal transplant patients with stable graft function

Abstract:  Conversion from MMF to EC-MPS may reduce GI complications and permit increased MPA dosing with a concomitant reduction in CNI dose. In a prospective trial, paediatric renal transplant patients with stable graft function were converted from MMF to EC-MPS and followed-up for 12 months. Data from 28 patients (mean age 13.9 ± 3.1 yr) were available for analysis. Mean EC-MPS dose increased significantly from conversion to month 12 (668 ± 81 mg/m²/day vs. 747 ± 98 mg/m²/day, p < 0.001). CsA-ME dose (n = 23) decreased from 5.3 ± 1.7 mg/kg/day at conversion to 4.6 ± 1.4 mg/kg/day at month 12 (p = 0.010). cGFR increased from 69.5 ± 23.3 mL/min/1.73 m² at the time of conversion to 80.7 ± 30.7 mL/min/1.73 m² at month 12 (p = 0.007). The number of patients reporting at least one GI event during six months prior to conversion was 15/28 (53.6%), declining to 8/28 (28.6%) at month 6 post-conversion and 5/28 (17.8%) at month 12. This single-arm study suggests that conversion of paediatric renal transplant patients from MMF to EC-MPS does not compromise efficacy and leads to improved GI tolerability. MPA dose increased and CsA-ME dose decreased significantly, with an associated improvement in calculated GFR. A large-scale controlled trial is required to confirm these promising findings.     

Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens

This paper reports results from an ongoing, randomized, multicentre national trial. The aim is to elucidate whether a dose of growth hormone (GH) of 0.2 IU/kg (0.07 mg/kg), given either as once-daily or twice-daily injections during puberty, is more effective than a once-daily dose of 0.1 IU/kg/day (0.03 mg/kg/day) in improving final height in children with GH deficiency (GHD). The twice-daily regimen comes closer to the spontaneous GH secretion pattern in puberty. Ninety-two children with GHD who had been receiving GH therapy for at least 1 year, and with spontaneous puberty or who were prepubertal and due to be started on replacement therapy to induce puberty, were randomly assigned to receive GH as follows: group A, 0.1 IU/kg/day (0.03 mg/kg/day), administered once daily; group B, 0.2 IU/kg/day (0.07 mg/kg/day), administered once daily; and group C, 0.2 IU/kg/day (0.07 mg/kg/day), divided into two equal injections given at 12-hour intervals. Pubertal height gain was 0.7, 0.7 and 1.3 SDS for groups A, B and C, respectively. The gain in height during puberty was thus most marked in group C. Mean final height, when corrected for parental height, was between 0 and 1 SDS in all treatment groups. All but seven children reached a final height within +/- 2 SD of the general population. There was a wide range of final heights in all three treatment groups. This variation in response suggests the need to individualize treatment in order to achieve an appropriate final height for most individuals.     

Reduced growth hormone secretion improves insulin sensitivity in adolescent girls with type 1 diabetes

The aims of the present study were to compare nocturnal growth hormone (GH) secretion, insulin requirements and insulin sensitivity on two occasions in six adolescent girls with type 1 diabetes when the GH secretion was reduced one night by an oral dose of 100 mg of pirenzepine at bedtime. The mean nocturnal intravenous insulin infusion required to maintain a normal constant blood glucose concentration between 24:00 and 07:00 was 53% higher during the night on placebo ( p = 0.0212). During the night on pirenzepine, the serum GH area under the curve (AUC) was reduced in all patients to a mean concentration which was 50.1% (15-78%) of that during the night without pirenzepine ( p = 0.0036). The nocturnal urinary GH excretion was also reduced in all of the investigated patients ( p = 0.0229). Insulin sensitivity in the morning, measured by the euglycaemic hyperinsulinaemic glucose clamp, increased significantly from 115±51mg m^-2 min^-1 after the night on placebo to 205±67 mg m^-2 min^-1 after the night on pirenzepine ( p = 0.0161). No side-effects were observed during the pirenzepine night. Negative correlations were found between the nocturnal serum GH AUC and the insulin-stimulated glucose metabolism ( r = 0.65, p = 0.0241) and between the nocturnal urinary GH excretion and the insulin-stimulated glucose metabolism ( r = -0.77, p = 0.0054). In conclusion, the present study shows a relation between GH secretion and insulin resistance in adolescent girls with type I diabetes. The administration of pirenzepine acutely reduces GH secretion and improves insulin sensitivity.     

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.     

A comparative study of growth hormone (GH) and GH-releasing hormone(1–29)-NH2 for stimulation of growth in children with GH deficiency

In this study, 60 patients with proven growth hormone deficiency (GHD) of hypothalamic origin were randomized into three equal groups, and received growth hormone-releasing hormone(1–29)-NH, (GHRH(1–29)-NH,), 30 or 60 μg/kg/day, or growth hormone (GH), 0.1 IU/kg/day, for 6 months. There were no significant differences in growth between the two groups given GHRH(1–29)-NH, but growth in the GH group was significantly better than in the other two groups ( p < 0.01). Mean height velocities at 6 months were 9.2, 9.3 and 14.6 cm/year for the three groups, respectively. Plasma GHRH concentrations increased steadily over the 6-month treatment period, with higher levels in the group on the higher dose. During GHRH(1–29)-NH₂ treatment, serum concentrations of insulin-like growth factor I rose initially, but then fell to values similar to those before treatment. No GH antibodies were detected, but all 20 patients on high-dose GHRH(1–29)-NH, and 19 of 20 patients on low-dose GHRH(1–29)-NH₂ developed GHRH antibodies. These had almost disappeared by 9 months after stopping treatment. There was no correlation between antibody titres and increase in height. No serious side-effects were seen, but three patients receiving GHRH(1–29)-NH, reported mild irritation at the injection site. These results from the continuous infusion of GHRH(1–29)-NH₂ over 6 months suggest that this treatment, or the related use of a depot preparation, is unlikely to be as effective as GH for the promotion of growth in GHD.     

Improved final height with long-term growth hormone treatment in Noonan syndrome

Aim: To assess whether children with Noonan syndrome on long-term growth hormone (GH) therapy improve their final height to near mid-parental height. Methods: Twenty-five prepubertal children (13 girls) with Noonan syndrome (NS) were studied. A single clinician made the diagnosis based on clinical criteria. GH treatment started at an age ranging from 3.1 to 13.8 y and was continued for at least 2 y. Improvement or “gain” in final height (FH) was defined as either the difference between adult height SD scores (SDS) and pre-treatment height SDS (the childhood component of the Swedish reference) or height SDS compared to the Noonan reference. Results: Ten children received a GH dose of 33 μg/kg/d (mean age at start 7.7±2.1 y, mean age at stop 17.6±1.7 y) and 15 received a dose of 66 μg/kg/d (mean age at start 8.6±3.3 y, mean age at stop 18.4±2.1 y). Eighteen out of 25 patients reached FH. A substantial improvement in FH of 1.7 SDS, equivalent to 10.4 cm compared to pre-treatment height, was observed. No significant difference was seen between the two GH doses. Females gained a mean height of 9.8 cm and males 1-13 cm (FH 174.5±7.8 cm vs mean adult height of 162.5±5.4 cm for males with NS) at final height. Moreover, 60% reached a mid-parental height of±1 SD.

Conclusion: GH treatment improves final height in patients with Noonan syndrome, with a mean gain of 1.7 SDS. The prepubertal height gain is maintained to final height and the children achieve a height close to their mid-parental height.     

A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis.

BACKGROUND: Turner syndrome accounts for 15-20% of childhood usage of growth hormone (GH) in the UK but final height benefit remains uncertain. The most effective strategy for oestrogen replacement is also unclear. METHODS: Fifty eight girls who, at start of treatment, were of mean age 9.1 years and projected final height 142.2 cm were randomised to receive in year 1, either low dose ethinyloestradiol 50-75 ng/kg/day, GH 28 IU/m(2) surface area/week as a daily injection, or a combination of ethinyloestradiol and GH. After the first year, the ethinyloestradiol treated girls received combination treatment. After two years, girls aged over 12 years were given escalating ethinyloestradiol to promote pubertal development. RESULTS: Near final height was available for 49 girls at age 16.5 years, 146.8 cm, representing a gain of 4.6 cm, range -7.9 to +11.7 cm. Twelve of the 49 girls gaining 7.5 cm or more were less than 13 years at the start and had received GH for at least four years. Height gain was correlated with greater initial height deficit. Fifteen girls (31%) reached 150 cm or more compared to a predicted 10%. Early supplementation with ethinyloestradiol provided no final height advantage. CONCLUSIONS: Final height gain was modest at 4.6 cm. Younger, shorter girls gained greatest height advantage from GH. Low dosage ethinyloestradiol before planned induction of puberty was not beneficial.