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Background: Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, feeding difficulties and failure to thrive in infancy. GH treatment improves growth velocity and body composition. Research on the effects of GH on psychomotor development in infants with PWS is limited., Objective: To evaluate psychomotor development in PWS infants and toddlers during GH treatment compared to randomized controls., Design/patients: Forty-three PWS infants were evaluated at baseline. Twenty-nine of them were randomized into a GH group (n = 15) receiving 1 mg/m(2)/day GH or a non-GH-treated control group (n = 14). At baseline and after 12 months of follow-up, analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age (%ed), and changes during follow-up were calculated., Results: Infants in the GH group had a median age of 2.3 years [interquartile range (IQR) 1.7-3.0] and in the control group of 1.5 years (IQR 1.2-2.7) (P = 0.17). Both mental and motor development improved significantly during the first year of study in the GH group vs. the control group: median (IQR) change was +9.3% (-5.3 to 13.3) vs.-2.9% (-8.1 to 4.9) (P < 0.05) in mental development and +11.2% (-4.9 to 22.5) vs.-18.5% (-27.9 to 1.8) (P < 0.05) in motor development, respectively., Conclusion: One year of GH treatment significantly improved mental and motor development in PWS infants compared to randomized controls.

Objective: In January 1997 we introduced a protocol for the treatment with GH of children with impaired growth after unfractionated total body irradiation (TBI). This study is an evaluation of that protocol., Patients and Methods: Between January 1997 and July 2005, 66 patients (48 male) treated for haematological malignancies had at least two years of disease-free survival after TBI-based conditioning for stem cell transplantation (SCT). Stimulated and/or spontaneous GH secretion was decreased in 8 of the 29 patients tested because of impaired growth. Treatment with GH (daily dose 1.3 mg/m2 body surface area) was offered to all 29 patients and initiated in 23 of them (17 male). The main outcome measure was the effect of GH therapy on height standard deviation scores (SDS) after onset of GH therapy, estimated by random-effect modelling with corrections for sex, age at time of SCT and puberty (data analysed on intention-to-treat basis)., Results: At time of analysis, median duration of therapy was 3.2 years; median follow-up after start of GH therapy was 4.2 years. The estimated effect of GH therapy, modelled as nonlinear (logit) curve, was +1.1 SD after 5 years. Response to GH therapy did not correlate to GH secretion status., Conclusion: GH therapy has a positive effect on height SDS after TBI, irrespective of GH secretion status.

Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH-IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH-IGF-I axis in order to describe the role of the GH-IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH-IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH-IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH-IGF-I axis for the patient and the therapeutic options will be discussed.

Background: Long term growth hormone (GH) treatment in children with idiopathic short stature (ISS) results in a relatively small mean gain in final height of 3-9 cm, which may not justify the cost of treatment. As it is unknown whether GH treatment during puberty adds to final height gain, we sought to improve the cost-benefit ratio, employing a study design with high dose GH treatment restricted to the prepubertal period., Aims: To assess the effect of short term, high dose GH treatment before puberty on growth, bone maturation, and pubertal onset., Methods: Five year results of a randomised controlled study are reported. Twenty six boys and nine girls were randomly assigned to a GH treatment group (n = 17) or a control group (n = 18). Inclusion criteria were: no signs of puberty, height less than -2 SDS, age 4-8 years for girls or 4-10 years for boys, GH concentration >10 micro g/l after provocation, and normal body proportions. To assess GH responsiveness, children assigned to the GH treatment group received GH treatment for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by three month washout periods, during the first year of study. High dose GH treatment (6.0 IU/m2/day) was then started and continued for at least two full years. When puberty occurred, GH treatment was discontinued at the end of a complete year's treatment (for example, three or four years of GH treatment)., Results: In response to at least two years on high dose GH treatment, mean (SD) height SDS for chronological age increased significantly in GH treated children from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years of study. No changes in height SDS were observed in controls. A rapid rate of bone maturation of 3.6 years/2 years in treated children compared to 2 years/2 years in controls was observed in response to two years high dose GH treatment. Height SDS for bone age was not significantly different between groups during the study period. GH treated children entered into puberty at a significantly earlier age compared to controls., Conclusions: High dose GH treatment before puberty accelerates bone age and induces an earlier onset of puberty. This may limit the potential therapeutic benefit of this regimen in ISS.

Since 1958 growth hormone (GH) has been used as substitution treatment for children with GH deficiency. At present, it is clear that a dose of 0.23 mg/kg/week can lead to a final height close to target height, but in view of the wide inter-individual variation, alternative regimens based on invidualizing the dosage with the help of prediction models are being investigated. The best strategy during puberty (increase the dosage, delay puberty) is still uncertain. The value of GH in idiopathic short stature is still heavily debated, although the average final height gain on 0.33 mg/kg/week is 5-7 cm. GH is efficacious in short stature due to chronic renal failure and Prader-Willi syndrome. In other conditions insufficient data are available. There are few side-effects.

Recombinant human GH therapy to children with idiopathic short stature (ISS) increases growth velocity, but its effect on final height (FH) is still uncertain. The aim of this study was to investigate the effect of recombinant human GH on FH of patients with ISS who were treated according to two protocols in comparison to untreated historical controls. In study 1 (n = 24), all patients were treated with 14 IU (4.6 mg)/m(2) body surface x wk in the first year; thereafter the dosage was doubled if the growth response was insufficient. In study 2 (n = 34), patients were randomized into three arms: 18 IU (6 mg)/m(2) x wk; 27 IU (9 mg)/m(2) x wk; and 18 IU/m(2) x wk in the first year, followed by 27 IU/m(2) x wk thereafter. Observed or estimated FH was available for 53 patients. Thirty-four untreated controls from the same centers were available for comparison. Mean FH SD score in GH-treated children was -2.1, vs. -2.4 in controls (-2.4) (NS), but height SD score gain (1.3 vs. 0.7) and the difference between FH and predicted adult height (4.0 vs. 0.8 cm) were significantly greater. The growth response on an initial dosage of 27 IU/m(2) x wk (6.9 cm) was significantly better than on other regimens (2.8 cm). We conclude that a GH dosage of 27 IU (9 mg)/m(2) x wk to prepubertal children with ISS leads to a mean FH gain of approximately 7 cm, whereas regimens starting on lower dosages are less efficacious.

The continuation of growth hormone treatment can be indicated in young adults who have been treated with growth hormone during childhood. However, in a large part of this population the diagnosis cannot be confirmed in adulthood. Therefore a retest procedure has to be performed once the final height has been attained. This procedure is only unnecessary in patients with deficiencies of two or more other pituitary hormone axes. The retest procedure can be performed one to three months after the growth hormone treatment has been discontinued, by means of an insulin tolerance test or, in the case of contraindications, by means of a combined growth hormone-releasing hormone(GHRH)-arginine test. If the growth hormone deficiency diagnosis is re-established, growth hormone treatment can be restarted. Patients are only eligible for a reimbursement of the growth hormone treatment costs from their health insurer, if the treatment indication is validated by the Dutch National Registry of Growth Hormone Treatment in Adults and the treatment results are included in a database. With this database insights into the long-term efficacy and safety of growth hormone treatment can be gained.

We studied the influence of recombinant human growth hormone (rhGH) on pubertal timing and pubertal growth in children with idiopathic short stature (ISS), and evaluated whether this was different between children with and without intra-uterine growth retardation (IUGR). Twenty-six (18 M, 6 IUGR; 'treated') subjects were treated with rhGH (6-7 days/week, dosage: 14-28 IU/m2 per week [i.e. 0.2-0.3 mg/kg per week]). Fifty-eight subjects (31 M, 9 IUGR; 'controls') were not treated. All subjects attained final height. Prepubertal height gain was significantly larger in the treated children compared to control children (M: 0.66 SDS, 95% confidence interval [CI] 0.41 to 0.92; F. 0.92 SDS, CI 0.58 to 1.26). Pubertal height gain, peak height velocity and duration of puberty were similar for the treated and control subjects. rhGH advanced the age at peak height velocity by 0.7 years (CI 0.3 to 1.0) in boys, and the age at onset of puberty by 1.1 years (CI 0.3 to 1.9) in girls. The gain in final height was 2-3 cm. Age and height SDS at start were the most important predictors for pubertal height gain, total height gain and final height in a multivariate regression analysis. Total height gain of treated subjects with IUGR was less than that of treated subjects without IUGR. In conclusion, rhGH did not affect pubertal growth in children with ISS, and slightly improved their final height. rhGH treatment should be started early to improve height as much as possible before the onset of puberty.

The efficacy of long-term growth hormone treatment and the optimal treatment modalities in Turner's syndrome are still controversial. Studies have shown widely divergent results. While there is still need for results of randomized controlled trials, large uncontrolled trials remain a valuable source of preliminary information. This study of 136 girls with Turner's syndrome (TS) from the European Lilly Turner Study shows that the treatment regimens followed by girls with TS who start GH treatment at a relatively late age (12.9 +/- 2.2 yr) lead at best to a small average gain in final height. Mean gain over initial projected final height was 3.7-4.7 cm, depending on the chosen Turner-specific height-for-age reference data. There was a considerable variation in gains over initial projected final height (range -10.6 to +17.2 cm), which may be partly explained by the existence of good and bad responders. Whether there is a genetic/molecular basis for this and how responsiveness can best be predicted remains an important challenge.

The aim of the study was to evaluate whether treatment with recombinant human growth hormone (rhGH) affects the quality of life of young adults who were diagnosed as idiopathic short stature (ISS) during childhood, and whether their quality of life and aspects of the personality are different from normal. Experiences and expectations concerning rhGH treatment of the subjects and their parents were also investigated. Eighty-nine subjects were included into the study: 24 subjects (16M, 8F) were treated with rhGH from childhood, whereas 65 subjects (40M, 25F) were never treated. At the time of the interview all subjects had attained final height [mean (SD) -2.3 (0.9) SDS for Dutch references], and the age of the treated subjects was 20.5 (1.0) y, and 25.7 (3.5) y of the control subjects (p < 0.001). The level of education was similar, but the treated subjects had less often a partner compared to the control subjects (adjusted for age and gender, p < 0.001). The Nottingham Health Profile and Short Form 36 Health Survey showed no difference in general health state between treated and control subjects, and the healthy Dutch age-specific references (norm group). Although 74% of the subjects reported one or more negative events related to their height, and 61% would like to be taller, only 22% and 11% were willing to trade-off at Time Trade-Off and Standard Gamble, respectively. The personality of the subjects, which was measured by the Minnesota Multiphasic Personality Inventory, was not different from the norm group. The satisfaction with the rhGH treatment was high, as it had caused 12 (8) cm and 13 (7) cm gain in final height according to the subjects and parents, respectively. Based on initial predicted adult height (Bayley & Pinneau), this gain was only 3.3 (5.6) cm. We concluded that although the treated subjects had a partner less often when compared to the control subjects, the quality of life of subjects with ISS at adult age is normal and appears not to be affected by rhGH therapy, The treated subjects were very satisfied with the treatment, probably by overestimation of the final height gain.

Objective: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV)., Design: Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]., Results: During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant., Conclusions: During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.

Long-acting gonadotropin-releasing hormone (GnRH) analogs (GnRH-a) suppress gonadal steroid production and are used in precocious puberty, resulting in an arrest of pubertal development, a slower epiphyseal maturation, and a deceleration of growth, but an increased final height. However, the way that GnRH-a affect growth is not clear. GnRH-a treatment might not only affect gonadal steroid production but might also modulate the GH axis and thereby affect growth. We used a rat model to investigate the long-term effects of prepubertally started GnRH-a treatment (triptorelin) on growth, spontaneous GH secretion, hepatic GH receptors (GHR), and GH-binding protein (GHBP) and compared it with surgical gonadectomy. Triptorelin affected most parameters in the same direction as surgical gonadectomy but to a lesser extent. In females, growth was enhanced by triptorelin, baseline GH secretion was decreased, and hepatic GHR and GHBP were decreased. Apart from these effects on the GH axis, reduction of the direct inhibiting effect of estrogen on growth could be responsible for the triptorelin-induced growth. In males, triptorelin treatment enhanced body weight gain and slightly enhanced gain in length. GH peak amplitude was the only parameter of GH secretion affected and decreased, whereas GHR or GHBP were not affected. This stimulation of weight gain by long-term triptorelin treatment in male rats, which is opposite the effect of surgical gonadectomy, could indicate an interference of GnRH-a in the hormonal regulation of food intake and body weight control. We conclude that triptorelin treatment affected growth and the GH-GHR-GHBP axis in rats, more markedly in females than in males. However, triptorelin was not as effective as surgical gonadectomy.

Growth hormone deficiency (GHD) is associated with truncal obesity. We aimed at identifying factors that determine the body mass index (BMI) of untreated GHD children and the changes in BMI during 2 years of GH therapy in 348 Dutch GHD children registered in the National GH Registration Database. BMI was expressed as a standard deviation score (SDS). Before GH therapy, the mean (95% CI) BMI-SDS in all GHD children (0.09 (-0.05 to 0.24) SDS) was comparable to normal children. Patients with GHD due to a cranial tumour have a higher BMI (1.03 (0.69-1.36) SDS; p < 0.0001) as well as those with multiple pituitary hormone deficiencies (0.35 (0.14-0.57) SDS; p = 0.005) and patients who are in puberty at start of GH therapy (0.60 (0.13-1.08) SDS; p = 0.036). During GH therapy BMI initially decreased to reach a nadir of -0.28 (-0.35 to -0.21) SDS at 6 months. Thereafter BMI progressively increased to -0.09 (-0.18 to -0.04) SDS after 24 months. A higher initial BMI-SDS resulted in a larger decrease in BMI-SDS. We showed that this can be sufficiently explained by a regression to the mean effect.

Unlabelled: GH is known to improve height velocity in girls with Turner syndrome (TS) but the optimal dosage regimen has yet to be defined., Objective: We attempted to improve the growth response by trying to mimic normal pulsatile GH secretion more closely., Design: In a 2-year study the effect of fractionated twice daily (BID) was compared with once daily (OD) s.c. injections of a total GH dose of 6 IU/m2/day. BID injections were administered as two-thirds at bedtime and one-third in the morning. The subjects concurrently received low dose ethinyl oestradiol (0.05 mg/kg/day, orally)., Subjects: Nineteen girls with TS aged 11 years or over, who were previously involved in a 10-week GH cross-over study., Measurements: Height and bone age were evaluated in relation to untreated Turner reference data. Final height (FH) was predicted using the Bayley and Pinneau (BP) method, the modified index of Potential Height (mIPHRUS), and a recently developed Turner-specific method (PTSRUS) based on regression coefficients for height (H), chronological age (CA) and bone age (BA). Plasma levels of GH, GHBP, IGF-1, and IGFBP-3 were determined by RIA., Results: After 2 years treatment the growth response expressed as HV, HVSDS, the change in HSDSCA, the gain in height over estimated untreated values and in FH prediction all showed significant improvements. Although mean values tended to be higher with OD injections, significant differences between groups were not found. Bone maturation was similar between groups and compared with untreated estimated values. Independent of treatment group, the change in HSDSCA after 2 years of GH treatment was related negatively to the baseline CA and HSDSCA, and positively to BA delay at baseline. After 18 months of GH treatment the significant decrease in GHBP plasma levels observed after 6 months was no longer significant. In contrast, IGF-1 and IGFBP-3 plasma levels and the IGF-1 to IGFBP-3 ratio increased significantly during 18 months GH therapy. None of these growth related factors showed a difference between groups in their 18 months change. Relevant side-effects were not observed during the first 2 years of GH treatment., Conclusions: The present growth data are in conformity with the data of the earlier 24-hour GH profiles. The growth response and plasma levels of growth related factors after 2 years GH on a total dose of 6 IU/m2/day in combination with low-dose oestrogens were not significantly different between the once daily and the twice daily GH injection regimen.

Height and weight growth before and during treatment with human growth hormone (hGH) was studied in 46 Dutch patients treated for craniopharyngioma. Weight was expressed as body mass index (BMI, weight/height). At the time of tumor treatment mean +/- SD height standard deviation score (SDS) was -1.22 +/- 1.38 and BMI SDS was 0.56 +/- 1.32. The initial height SDS was inversely related to age (r = -0.38; p < 0.02). Before hGH treatment height SDS decreased to - 1.57 +/- 1.08 (p < 0.05) and BMI SDS increased to 1.54 +/- 1.58 (p < 0.005) during the first year after tumor treatment. Changes in height SDS correlated positively with basal prolactin (PRL) levels (r = 0.46; p < 0.05). Neither tumor localization nor treatment mode was related to changes in height SDS and BMI SDS. Forty patients were treated with hGH, started a median interval of 2.0 years after tumor treatment. At the time of the start of hGH treatment height SDS in these patients was -1.70 +/- 1.13, and BMI SDS was 1.44 +/- 1.79. During treatment with hGH, height SDS increased to -1.05 +/- 1.10 (p < 0.001) in the first, and to -0.80 +/- 1.04 (p < 0.001) in the second year. BMI SDS did not change during hGH therapy. In conclusion, there is a large variation in height SDS and BMI SDS at the time of initial presentation as well as during spontaneous growth after tumor treatment. Spontaneous growth is related to serum PRL concentrations. Treatment with hGH significantly increased height SDS during the first 2 years, whereas BMI SDS did not change.

Isolated idiopathic growth hormone deficiency (GHD) and idiopathic short stature (ISS) can be difficult to distinguish, but the therapeutical consequences are different. In this report the data on final height of untreated and treated children with GHD and ISS are reviewed. Untreated GH-deficient individuals who underwent spontaneous puberty (22 male, 14 female patients) reached a mean final height of 4.7 SD (range 3.9 to 6.0) below the population's mean. If puberty was induced (19 male patients), mean final height SD score (SDS) was -3.1. Traditional regimens of GH administration (2-4 injections/wk) in 236 children (184 boys, 52 girls) with GHD and spontaneous puberty resulted in a final height SDS of -2.8 (range -1.5 to -4.7). In 190 children in whom puberty was induced (139 boys, 51 girls) mean final height was -1.6 (range - -1.1 to -2.4). The mean gain in final height SDS is therefore estimated at 1.5-2.0 in average cases, and 3.5 in extreme cases. Preliminary data suggest that on present regimens mean final height may approach target height. In untreated boys with ISS the mean final height was 2-5 cm lower than that predicted before puberty, whereas in girls it was almost equal to the prediction. After GH treatment the mean final height was 0.4-3.0 cm higher than the predicted adult height, which results in an average net gain in final height SDS of approximately 0.5-0.8 (3-5 cm).

Objectives: To study final height after long-term growth hormone (GH) treatment in girls with Turner syndrome (TS)., Patients: One hundred fifty three patients with TS, participating in five European trials, were included. They started GH treatment in 1987-1989 at an age of 10 years or older. Mean age at start of treatment ranged between 11.7 and 14.6 years among countries and mean bone age between 9.4 and 11.8 years. Fourteen girls were lost to follow-up, leaving 139 for analysis. Most girls have now attained final height (FH), defined as a linear growth velocity (GV) of 4 mm/yr or less, measured over at least 6 months (group 1, n = 56), or near-FH, defined as a GV of 5 to 9 mm/yr (group 2, n = 22). Sixty-one girls were still growing 10 mm/yr or more., Methods and Main Results: At the last measurement, mean (SD) height was 150.7 (4.9) cm in group 1 and 148.5 (5.1) cm in group 2. The differences between FH and projected final height based on extrapolation of the initial height-standard deviation score on Turner syndrome reference values, were 2.9 (3.8) and 3.0 (3.3) cm, respectively. The mean gain over the Bayley-Pinneau prediction of FH was 3.3 (3.9) cm in both groups. No significant differences between countries were found. The range of gains over projected height (-4.7 to 12.1 cm) was large, and 25% of gains were 5 cm or more. Gain over initial projection was strongly related to initial growth delay and to growth response during the first 2 years of treatment. A logistic regression model is presented that predicts gain of more than 5 cm with a positive predictive value of 62% and a negative predictive value of 84%., Conclusions: Long-term GH treatment in girls with TS, starting treatment at a relatively advanced age ( > 10 years) resulted in a modest mean gain in FH of 3 cm, with wide interindividual variation.

Objectives: In adults with growth hormone deficiency (GHD) social problems have been reported, but so far the relative contributions of GHD, additional pituitary deficiencies and short stature have not been distinguished. We therefore compared social data from GHD patients with social data from controls with short or normal stature. Furthermore we investigated whether social problems are caused solely by the deficiency of GH or also by the associated absence of other pituitary hormones., Design: A questionnaire was sent to patients and controls with items on education, profession, income, partner and living situation., Patients: Two hundred and ten GHD patients treated in childhood but not in adulthood with GH (93 isolated GHD (IGHD), 111 patients with multiple pituitary deficiency (MPD)) were compared with 53 short controls (height in childhood < third percentile for population) and 39 normal stature controls., Results: There were no differences between short and normal controls. There were also no differences between IGHD and MPD patients in any of the investigated items. GHD patients did not differ from controls on education level, but scored lower on the profession scale, had a lower income and had a partner less often; if they had a partner they less often had children; also, more of them lived with their parents., Conclusion: Since patients with multiple pituitary deficiency did not differ from patients with isolated growth hormone deficiency, this suggests that the lower scores on the social parameters are the result of the growth hormone deficiency itself. Since short stature controls had higher scores than patients with growth hormone deficiency and did not differ from normal stature controls in any of the aspects investigated, it seems unlikely that the problems of the patients with growth hormone deficiency can be attributed to short stature.

Catch-up growth of 26 children with growth hormone deficiency during four years of growth hormone treatment, which was started young (< 3 years), was compared with that of 16 children with coeliac disease on a gluten free diet. In children with growth hormone deficiency mean (SD) height SD score increased from -4.3 (1.8) to -1.9 (1.4) and in patients with coeliac disease from -1.8 (0.9) to -0.1 (0.8). Height SD score after four years correlated positively with injection frequency and height SD score at start of treatment in children with growth hormone deficiency. All patients with coeliac disease reached a height above -2 SD scores after four years, while the height of 26% of children with growth hormone deficiency on daily injections and of 86% of children on 2 or 4 injections/week was still below -2 SD scores. In patients with growth hormone deficiency on daily injections with an initial height SD score between -2 and -4 catch-up was similar to that of patients with coeliac disease with a comparable initial height deficit. Growth hormone deficient children with an initial height SD score < -4 did not reach full catch-up growth within four years. In conclusion, catch-up growth in early treated children with growth hormone deficiency over four years is adequate provided that daily injections are given and the initial height SD score is not less than -4.

Normal rats are sexually dimorphic in their growth and GH secretion. Gonadectomy (Gnx) changes the GH secretory pattern and this could explain differential growth rates in male and female rats. Gonadal steroids may also affect tissue growth directly, or by changing their responsiveness to GH. The effects of Gnx on growth, GH responsiveness, and hepatic GH receptors have now been studied in young (4-7 weeks old) GH-deficient dwarf rats in which the effects of steroid-induced alterations in residual endogenous GH secretion will be much less pronounced. Groups of intact and Gnx dwarf rats (n = 5-7) were infused with recombinant human GH (144 micrograms/day) either continuously or in a pulsatile pattern (every 3 h) for 7 days, whilst control groups received saline infusions. Gains in weight, length and tibial bone growth were measured. Female dwarf rats grew significantly more slowly than male dwarfs. Gnx in male dwarfs inhibited growth significantly, whereas ovariectomy had a lesser stimulatory effect in females. Hepatic lactogenic and somatogenic receptors were higher in females and ovariectomy lowered their values towards male levels. Pulsatile GH infusions were more effective than continuous infusions of the same daily GH dose, but when the different underlying growth rates (measured in saline-infused Gnx animals) were taken into account, the responsiveness to pulses of hGH was not different between males and females or between intact and Gnx animals. We have concluded that Gnx in dwarf rats does affect growth, but the effects are small in comparison with those seen in normal rats. Since pulsatile GH infusions stimulated growth more effectively than continuous GH, irrespective of the gonadal steroid status, and the responsiveness to exogenous GH was not changed by Gnx, the results imply that changes in the GH secretory pattern induced by gonadal steroids may have a larger impact on the growth rate than direct effects at the tissue level, at least in the rat.

Background and Objective: Growth hormone treatment in children with idiopathic short stature (ISS) leads to growth acceleration in the first years, but the effect on final height is still poorly documented. We therefore studied the long-term effect of GH therapy in children with idiopathic short stature., Design: We have treated 27 prepubertal children with ISS with recombinant human GH (rhGH) in an initial dosage of 2 IU/m2 body surface/day subcutaneously, which was doubled either after the first year if the height velocity increment was less than 2 cm/year, or thereafter if height velocity fell below the P50 for bone age. Growth and bone maturation of the treatment group (ISS group, n = 21) were compared to those of an untreated control group with ISS (ISS controls, n = 27) and of a group of rhGH treated children with isolated GH deficiency (GHD group, n = 7)., Results: In 9 patients of the ISS group still on treatment, height standard deviation score (HSDS) for chronological age increased from -3.8 +/- 0.7 to -2.3 +/- 0.9 (mean +/- standard deviation) over 6 years, while in matched ISS controls HSDS for age did not change. HSDS for age in the GHD group increased from -3.9 +/- 0.6 to -1.8 +/- 0.7 after 4 years, significantly more than the ISS group. Bone maturation was accelerated in the ISS and GHD groups. HSDS for bone age and predicted adult height did not change in either group. Final height in 12 children of the ISS group was -2.6 +/- 1.0 SDS. In the untreated controls final height was similar. A low integrated GH concentration over 24 hours, a low GH peak to provocative stimuli, and minimal initial BA delay predicted a favourable outcome., Conclusion: rhGH treatment in this group of children with idiopathic short stature did not increase average final height. Part of the heterogeneity of the response can be attributed to the variation in endogenous GH secretion and initial bone age delay.

Final height was evaluated in 203 patients with growth hormone (GH) deficiency, who had been treated with GH in childhood, and was related to other factors. Mean final height was 168.1 cm (men) and 154.7 cm (women), -2.07 and -2.20 SD of the population mean, respectively. Patients with GH deficiency due to cerebral tumour were taller than those with idiopathic GH deficiency, and patients with induced puberty were taller than those with spontaneous puberty. Target height (r = +0.37), birth length (r = 0.36), height SDS at the start of therapy (r = +0.51) and at the start of puberty (r = +0.58) were significantly correlated with final height. Multiple linear regression analysis revealed that after correction for height at the start of puberty, age at the start of puberty was also positively correlated with final height. Patients who were treated after 1983 (when treatment regimens were changed) were taller than patients who finished treatment before 1983. The results suggest the importance of preventing a large initial height deficit and attaining optimal height at the start of puberty.

In 1987 a multicentre trial of recombinant human growth hormone (GH) was started in girls with Turner syndrome. Fifty-four patients were randomly assigned to receive GH, 8 IU/m2 3 times/week (group 1), or 4 IU/m2 6 times/week (group 2). In addition, the 35 patients older than 12 years received ethinyloestradiol, 100 ng/kg body weight/day, and after 2 years GH therapy was increased to 6 IU/m2 6 times/week. Recombinant human GH treatment was stopped when the height increment during the previous 6 months of treatment was less than 0.5 cm. Treatment has so far been stopped in 48 patients: treatment was stopped early in 2 patients due to lack of motivation, 1 patient died suddenly and the treatment protocol was completed in 45 patients. The last height measurement obtained, which was considered as (near) final height, was 152.3 +/- 5.3 cm (mean +/- SD) in these patients, which is higher (p < 0.001) than the adult height of 147.0 +/- 6.3 cm reported in 63 untreated adult Dutch patients with Turner syndrome. No differences in outcome were found between the two dose regimens.

In 34 children with idiopathic short stature (ISS) we studied parameters of humoral and cellular immunity before and during growth hormone (GH) therapy. The patients were treated with recombinant human GH 3.0 or 4.5 IU/m2 body surface/day, 6 times/week. Leucocyte and lymphocyte counts, percentages of neutrophils, eosinophils, basophils and monocytes were available up to 4 years of therapy (n = 34) and lymphocyte subsets and serum immunoglobulins during the first year of treatment (n = 16). Differences between the measurements at the start and during therapy were tested by a mixed model ANOVA to repeated measurements. Before the start of GH therapy all parameters of immunity were within the normal range in these children. During the first months of treatment the leucocyte and lymphocyte counts decreased and at 6 months were significantly lower than at the start (p = 0.003 and p = 0.006, respectively). Thereafter leucocyte numbers no longer differed from baseline. Lymphocytes were again lower at 36 months (p = 0.001). The percentages of neutrophils, eosinophils, basophils, monocytes and lymphocyte subsets did not change during therapy. Serum IgA concentrations showed a transient decrease at 3 and 6 months of GH therapy (p = 0.01 and p = 0.02). The observed changes were not related to GH dosage or height velocity. We conclude that GH treatment in children with ISS induced a small decrease in leucocyte and lymphocyte counts and serum IgA concentrations.

The comparative effect and safety of 2 IU compared with 4 IU/m2/day of recombinant human growth hormone (rhGH) was studied in 38 growth hormone deficient children regarding the impact of several factors on short term (one year) and long term (three year) growth response. In 21 newly diagnosed patients, three years of rhGH treatment resulted in a significant increase of height velocity SD score, height SD score, and predicted adult height SD score, irrespective of rhGH dose. In 17 transfer patients (previously treated with 12 IU rhGH/m2/week) 4 IU/m2/day resulted in a significantly higher height velocity SD score and height SD score for chronological age than 2 IU/m2/day, while more of them reached their target range or showed a substantial height SD score increment. Height SD score for bone age and predicted adult height SD score only increased significantly with 4 IU rhGH. After one year of rhGH treatment, new patients showed significant negative correlation between delta height SD score with age and baseline insulin-like growth factor I (IGF-I) SD score, and positive correlation with rhGH dose. After three years of treatment, delta height SD score for chronological age was significantly, negatively correlated with age and baseline 'corrected' height SD score (height SD score for chronological age minus target height SD score). There was no significant correlation with rhGH dose. Prolonged treatment with either dose had no adverse effect on IGF-I concentrations, carbohydrate or lipid metabolism. As early age and divergence between height SD score and target height SD score seem more important for growth response than rhGH dose, it is recommended that treatment starts early with 2 IU rhGH/m(2)/day and the dose is doubled if growth is insufficient after several years of treatment.

Spontaneous growth and growth responses to GH therapy vary considerably among girls with Turner's syndrome. In an attempt to clarify this variability, we assessed growth parameters, 24-h GH profiles, arginine-stimulated serum GH levels, and plasma insulin-like growth factor-I (IGF-I) concentrations in a group of 41 girls with Turner's syndrome with a mean (+/- SD) age of 13 +/- 3 yr (range, 6.7-18.9). We subsequently treated all girls with biosynthetic GH (24 IU/m2 x week) and documented the growth response after 1 yr of therapy. GH profiles were analyzed according to Pulsar and Cluster, and GH secretion rates were calculated by waveform-independent deconvolution (Pulse). Factor analysis selected the mean 24-h GH secretion rate and number of GH peaks according to Cluster and Pulse as the principal GH profile variables to be used for further analysis. The mean (+/- SD) daily pituitary GH secretion rate was 127 +/- 47 micrograms/L.24 h (range, 37-232). The GH secretion rate correlated inversely with body mass index (r = -0.45; P < 0.01; n = 41). There was no relationship between the GH secretion rate and the growth parameters before or after GH therapy. However, the number of GH peaks (Pulse) correlated negatively with baseline height velocity (r = -0.53; P = 0.03) and was a positive predictor for height velocity increment during the first year of GH therapy (r = 0.71, P = 0.001). The mean (+/- SD) IGF-I level was 217 +/- 91 ng/mL (range, 87-413). There was no relationship between GH secretion rate or growth parameters and IGF-I. However, the number of GH peaks correlated negatively with IGF-I (r = -0.49; P = 0.04; n = 17). We conclude that an elevated spontaneous GH pulse frequency pattern is associated with relatively low IGF-I levels and slow baseline growth in girls with Turner's syndrome and that girls with such a pulse pattern may benefit most from exogenous GH therapy.

Girls with Turner syndrome were divided according to age (group A 6-12 years, and group B 12-19 years) and human growth hormone (GH) dose regimen (A1 and B1, three injections/week; A2 and B2, six injections/week). All groups responded to GH, 24 IU/m2/week, with an increase in height velocity, though in the older girls, the response was comparatively poor. Therefore, the dose regimens in groups B1 and B2 were increased to 36 IU/m2/week given as six injections in both groups. This change resulted in an increase in height velocity only in group B1. During the first 2 years only, the height velocity was greater in group A2 than group A1. The conclusion is that a regimen of six injections/week is more effective than one of three injections/week in terms of initial height gain and change in predicted adult height. In girls with Turner syndrome aged over 16 years, GH therapy has no significant effect.

In vivo studies in experimental animals and in vitro studies using human lymphocytes have indicated that growth hormone (GH) is important for the development and function of the immune system. This is most clearly illustrated by the underdevelopment of the thymus in dwarf Snell mice, which is prevented by GH treatment. In contrast, in vivo studies in humans have generally shown only minor alterations of immune function in GH deficiency. GH administration to children with various growth disorders may lead to variable and subtle changes in some laboratory parameters of immune function, but no clinical symptoms associated with immune dysfunction have been reported.

Abnormalities of immune status, particularly a high prevalence (about 50%) of thyroid autoantibodies, have been reported before in Turner syndrome. Results are conflicting as regards other abnormalities of immune function. Growth hormone (GH) has immunomodulatory effects, but results of its effects on GH-deficient children are inconsistent. In this study, 42 girls with Turner syndrome, aged 7.3-19 years, are investigated before, during and after 4 years of human GH therapy. Girls over 12 years old also received ethinyl oestradiol. The prevalence of antithyroid antibodies was 16.7% initially, 35.3% after 24-45 months and 48% after 4 years of therapy though, as there was no control group, it was difficult to conclude that GH was enhancing their appearance. Hypothyroidism was extremely uncommon, and the growth response was no different in those who had the antibodies from those who had not. There were no dramatic increases in prevalence of any of the other antibodies investigated, though the prevalence of parietal cell antibodies was higher than expected.

Most children with idiopathic short stature can be classified under the diagnoses familial short stature and constitutional delay of growth and adolescence. Administration of growth hormone leads to faster growth, but also faster bone maturation. Daily injections are more efficacious than three injections per week. There is a dose-response relationship. In a Dutch prospective study, the acceleration of growth was only slightly more than bone age advance, so that the average predicted adult height increased only by 3 cm over a period of 4-5 year. In an untreated control group final height was 1 cm lower than predicted. There were great inter-individual differences in terms of growth and bone maturation, which could not be predicted on the basis of clinical and biochemical variables.

Short stature is a feature in almost all cases with Turner syndrome. The etiology is unknown, but GH secretion appears to be normal. The treatment with anabolic steroids does not seem to increase final height. Oestrogens are needed for secondary sex characteristics, but should be given in a low dosage and at approximately 12-13 years of age, in order not to compromise final height. Growth hormone increases growth velocity and leads to an average gain of 5 cm in terms of final height. The addition of oxandrolone leads to an even higher growth rate, but final height is probably similar to that reached by growth hormone alone. The dosage, injection frequency, age and bone age at the start of therapy have influence on the efficacy. GH in the dosages given appears safe.

The history of growth hormone treatment can be divided into two episodes. Between 1958 and 1985 growth hormone was extracted from human pituitaries. Because of the scarcity little scientific research was carried out and efficacy was not optimal. In 1985 biosynthetic growth hormone became available, which facilitated research on the use of growth hormone for various indications. In the future further research is needed on the pathophysiology of growth disturbances, on methods to improve efficacy, and on possible side-effects of pharmacological dosages.

Sixteen girls with Turner syndrome (TS) were treated for 4 years with biosynthetic growth hormone (GH). The dosage was 4 IU/m2 body surface s.c. per day over the first 3 years. In the 4th year the dosage was increased to 6 IU/m2 per day in the 6 girls with a poor height increment and in 1 girl oxandrolone was added. Ethinyl oestradiol was added after the age of 13. Mean (SD) growth velocities were 3.4 (0.9), 7.2 (1.7), 5.3 (1.3), 4.3 (2.0) and 3.6 (1.5) cm/year before and in the 1st, 2nd, 3rd and 4th year of treatment. Skeletal maturation advanced faster than usual in Turner patients especially in the younger children. Although the mean height prediction increased by 5.6 cm and 11 of the 16 girls have now exceeded their predicted height, the height of the 4 girls who stopped GH treatment exceeded the predicted adult height by only 0 to 3.4 cm.

In view of contradictory reports on the growth hormone dependency of early postnatal growth we studied the growth curves of 15 infants with neonatal growth hormone deficiency. In seven infants the growth curve was parallel to the standards of the infancy-childhood-puberty (ICP) model (group 1), but in the remaining infants there was an immediate deviation of the growth curve (group 2). In this group the mean (SD) at 4 and 9 months of age was -3.3 (1.1) and -4.9 (1.4), respectively, when compared with the ICP model. The mean birth length in both groups was decreased and five out of 15 had a birth length of less than -2 SD. Serial measurements of the growth hormone response to provocation tests in two patients in group 2 showed decreasing concentrations, while four patients with documented complete growth hormone deficiency belonged to group 2. We conclude that growth hormone is needed for early infant growth and that the normal growth pattern in some infants with neonatal pituitary dysfunction is due to incomplete insufficiency.

Study Objective: To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner's syndrome., Design: Randomized study., Setting: Referral-based pediatric endocrinology departments of seven university medical centers., Patients: Fifty-two patients with Turner's syndrome confirmed with chromosomal analysis., Treatment: Somatotropin recombinant DNA (24 IU/m2 of body surface area) subcutaneously administered in three or six injections per week for 2 years. Patients who were older than 12 years at the beginning of the study received low doses of estrogen., Results: The following statistically significant findings supported the use of six injections per week compared with three injections per week: the mean (+/- SD) increment in height during 2 years was 11.3 cm (3.8 cm) with six injections vs 8.6 cm (3.4 cm) with three injections; the increment in height standard deviation score was 0.9 cm (0.5 cm) vs 0.6 cm (0.3 cm); the growth velocity was 6.6 cm/y (2.0 cm/y) vs 5.2 cm/y (1.7 cm/y) in year 1 and 4.7 cm/y (2.0 cm/y) vs 3.4 cm/y (1.7 cm/y) in year 2; and the increment in height standard deviation score for bone age was 0.8 cm (0.5 cm) vs 0.4 cm (0.6 cm). For patients whose initial bone age was more than 13 years, growth velocity increased by 1 to 2 cm in year 1; in year 2 no increment was observed. We did not observe adverse effects., Conclusions: Biosynthetic growth hormone in a higher-frequency regimen in Turner's syndrome is more efficient in terms of increment in height, growth velocity, and height standard deviation score for bone age than treatment in a lower-frequency regimen. In patients with an initial bone age of more than 13 years, the response was poor. Longer follow-up is necessary to assess the effect on final height.

Twenty-four-hour growth hormone (GH) profiles in 26 girls with Turner's syndrome were compared with those of 26 normally growing short children and 24 slowly growing short children. All children were prepubertal and below 12 years of age. A subgroup of 13 girls was treated with ethinyl estradiol and a 24-h GH profile was reassessed. In an additional group of 45 girls with Turner's syndrome (aged 6.7-18.9 years) the effect of age, spontaneous breast development and ethinyl estradiol treatment was studied. The profiles were assessed by Fourier analysis. The oscillatory activity and the mean 24-h GH concentration were similar in children with Turner's syndrome and the normally growing short children, in contrast to lower levels in the slowly growing short children. The periodicity of GH secretion was similar in all groups. In the longitudinal study, ethinyl estradiol treatment resulted in a significant increase in pulse amplitude, but not in periodicity. In the cross-sectional study there was no significant difference between the subgroups of girls with either presence or absence of breast development or ethinyl estradiol treatment. GH secretion was not significantly related to age, height in standard deviation score or height velocity. These data imply that there is no abnormality in GH secretion in girls with Turner's syndrome.

A multicenter dose-response study evaluated the effect of two different doses of biosynthetic GH on auxological and biochemical parameters in 38 prepubertal children with GH deficiency (GHD). Twenty-one were newly diagnosed, while 17 transfer patients had been on GH treatment for at least 1 yr before the study. New and transfer patients alike were treated with either 2 or 4 IU GH/m2.day sc. At evaluation all new patients had completed 1 yr of treatment, while transfers had completed 2 yr of treatment under study. In the new patients both doses resulted in a significant increase in height velocity (HV) and height SD score (SDS), with comparable bone maturation. After correction for the severity of GHD, the increase in HV SDS was significantly greater with 4 IU than with 2 IU (P less than 0.01). In the transfer patients HV, height SDS, and predicted adult height only increased significantly with 4 IU (P less than 0.05). Bone maturation was comparable for the two doses. There was a significant correlation between first year growth response and GH dose. In the new patients, the plasma insulin-like growth factor-I (IGF-I) concentration increased significantly without a significant difference between dosage groups. There was a positive correlation between growth response and increment of plasma IGF-I SDS. In new and transfer patients alike, above normal plasma IGF-I levels were observed, particularly with 4 IU. Hemoglobin-A1 remained constant with both GH doses in both groups, while cholesterol and LDL levels tended to decrease. In the new patients, the mean apolipoprotein-A1 level was lower than the control value after 1 yr on 4 IU GH. Treatment with 4 IU GH/m2.day led to a greater growth response than a dose of 2 IU in newly diagnosed as well as previously treated GHD patients. Bone maturation was comparable for both doses. No adverse effects were observed with the higher GH dose, but the long term effects on IGF-I and lipid metabolism need further attention.

Daily pituitary growth hormone (GH) secretion can be estimated from a 24-hour GH profile by various methods. We have used four methods to assess GH secretion in 36 girls with Turner's syndrome: the method described by Thompson et al., the Pulsar algorithm combined with the method of Hellman et al. and two deconvolution techniques. The number of detected peaks varied considerably among the methods. The mean (+/- SD) total daily secretion per square meter body surface was 0.53 (0.19) U/m2.day by deconvolution, in contrast to 0.31 (0.17) with the Hellman method and 1.06 (0.37) according to Thompson. The differences are explained by different assumptions about the metabolic clearance rate and various methodological aspects. Assuming a degradation rate of 50%, the growth hormone substitution dosage would be 1-2 IU/m2.day in GH-deficient children. The usual dosage in girls with Turner's syndrome is expected to lead to serum GH levels approximately 4 times higher than in the untreated state.

Stunted growth is a serious problem for children with chronic renal failure (CRF) despite normal endogenous growth hormone secretion and normal or elevated plasma concentrations of insulin-like growth factors (IGF) I and II. Biosynthetic growth hormone (GH) was given to 20 prepubertal children (eleven boys, nine girls; mean age 9.5 years, range 4-16) with CRF and severe growth retardation in a placebo-controlled, double-blind, cross-over trial. 6 months of subcutaneous injection of GH (4 IU/m2 per day) was either preceded or followed by 6 months of placebo injection. The patients had a full examination every 3 months. Sixteen children completed the study. Height velocity improved significantly with GH therapy (p less than 0.0001) and placebo (p less than 0.04), but the GH-induced height-velocity increase exceeded that of placebo by 2.9 cm per 6 months. There was a positive relationship between prestudy height velocity and height-velocity increase. Bone maturation was not affected. GH caused a significant increase in IGF-I and a moderate increase in IGF-II plasma concentrations. The pretreatment elevation of IGF-binding protein-1 decreased by almost 50% during GH therapy, while IGF-binding protein-3 increased significantly in concentration, although this increase was significantly smaller than the GH-induced increase in IGF-I. Fructosamine, lipid, and parathyroid concentrations remained constant. Renal function deterioration did not accelerate. Impressive height-velocity increase can be achieved with GH therapy in children with CRF and growth retardation without changes in renal function. Bone maturation appears unaffected suggesting improved final height. Treatment is best started before growth retardation becomes considerable.

Immunologic studies of 14 girls with Turner syndrome were done before and during treatment with biosynthetic growth hormone (GH). Compared with control subjects, the patients before treatment had a decreased CD4/CD8 ratio and an increased number of cells bearing the natural killer cell marker CD16; serum immunoglobulin levels were within the normal range. During GH treatment some of the girls had a slight reduction in the percentage of CD20+ B cells, but we observed no impairment of B lymphocyte function as demonstrated by the normal in vivo antibody response to the primary antigen Helix Pomatia hemocyanin, administered 6 months after the start of GH treatment. The number of CD16+ natural killer cells returned to normal. Although the number of children with thyroid antibodies increased from two before treatment to five after 1 year, no conclusion about an adverse effect of GH is warranted, because the phenomenon might be part of the natural course of the disease. We conclude that girls with Turner syndrome have minor changes in some immunologic measurements and that GH treatment resulted in some alterations that have no effect on immune function.

Congenital nemaline myopathy (CNM) is generally classified as a non-progressive or slowly progressive neuromuscular disease. We describe a boy with CNM and an isolated partial growth hormone (GH) deficiency. From the onset of GH therapy his respiratory capacity deteriorated rapidly. The possible association between this deterioration and GH therapy is discussed.

We studied 24-h plasma GH profiles, maximal GH responses to arginine provocation and insulin-like growth factor-I (IGF-I) and IGF-II levels in plasma in 22 euthyroid prepubertal children (mean age, 9.5 yr) with chronic renal insufficiency (glomerular filtration rate, less than 20 mL/min.1.73 m2) and severe growth retardation [mean (+/- SD) height SD score (SDS), -2.8 (1.1)]. The 24-h GH profiles were analyzed using the Pulsar program. Girls had significantly higher 24-h GH secretion than boys (P less than 0.004). Children with end-stage nephrotic syndrome had higher baseline GH levels and total area under the curve (AUCo) than patients with dysplastic kidneys (P less than 0.05), while the area under the curve above baseline (AUCb) was similar in all types of renal diseases. The type of treatment (conservative, peritoneal, hemodialysis) did not significantly influence the 24-h GH secretion. No correlation was found between 24-h GH profiles and age, height SDS for chronological age, height velocity SDS for bone age, and weight for height. Fourteen children showed a normal 24-h GH profile, defined as a GH profile with well defined, regular GH peaks returning to baseline GH levels and a distinct day and night pattern (AUCb, 90-300 micrograms/L.24 h). Four children had low profiles, with GH peaks below 10 micrograms/L, returning to baseline GH levels and occurring almost exclusively during the night (AUCb, less than 90 micrograms/L.24 h). The remaining four children had elevated 24-h GH profiles, with GH peaks on top of elevated baseline GH levels of more than 3 micrograms/L (AUCb, 35-205 micrograms/L.24 h; AUCo greater than 300 micrograms/L.24 h). In all patients 24-h urinary GH and beta 2-globulin excretion was 100-1000 times higher than that in controls. The urinary GH excretion correlated significantly with all characteristics of the 24-h GH profiles (r = 0.57-0.59; P less than 0.05). The maximal GH response during the arginine tolerance test was normal in 66% of the children. The mean (+/- SD) SDS for bone age for the IGF-I plasma levels was +1.1 (1.9), and that for IGF-II was +3.6 (3.4). IGF-I levels correlated significantly with the AUCb, maximum GH, and GH peak characteristics of the 24-h GH profiles (r = 0.05-0.73; P less than 0.02-0.001). IGF-II levels did not show any correlation with the characteristics of the endogenous GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

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 microgram/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.