Growth hormone therapy for 3 years: The OZGROW experience

Objective : To examine the growth response over 3 years of growth hormone deficient (GHD) and non-GHD children who have received growth hormone (GH) in Australia.
Methodology : A retrospective study of a group of patients (1362 children) who commenced GH prior to 1 September 1990. Data were collected at 12 growth centres located in major cities throughout Australia. The data were transferred after informed consent to the national OZGROW database located at the Royal Alexandra Hospital for Children, Sydney, NSW. Of the 1362 children, 898 had received 3 years or more GH therapy and were eligible for this analysis. This cohort was then categorized by diagnosis. Growth response was assessed using height standard deviation score, estimated mature height, growth velocity (GV), GH dose and bone age (years).
Results : For children who completed 3 years therapy, the baseline characteristics among diagnostic groups were similar with mean height standard deviation score (SDS) less than – 3 SDS (except for the malignancy group) and mean GV ranging from 3.5 to 4.4 cm/year. The GV during the first year improved in all groups (7.7-9.4 cm/year) followed by an attenuated response during the second and third years of therapy. After 3 years GH therapy the GHD group with peak levels <10 mU/L demonstrated the greatest change in estimated mature height and height SDS. The GHD group with peak levels between £10 but <20 mU/L had a growth response similar to the non-GHD children for all outcome parameters. Change in bone age ranged from 3.1 to 3.8 years with no differences being noted between the diagnostic groups, nor consistently with pubertal status.
Conclusions : Australian GH guidelines have targeted very short children when compared to other series. This large cohort of non-GHD children has demonstrated short-term benefits of GH therapy; however, the long-term benefit remains unclear until these children reach final adult height.     

Testing with growth hormone-releasing factor (GRF(1–29)NH2) and somatomedin C measurements for the evaluation of growth hormone deficiency

Growth hormone (GH) responses to GRF (1 μg/kg BW i.v.) were investigated. Comparison between GRF(1–40) and GRF(1–29)NH2 in 11 young adult volunteers gave identical results. One hundred and thirty-one children and adolescents (45 with idiopathic GHD) were tested with GRF (1–29)NH2. The maximal GH levels (max GH) in response to GRF during the 120 min test period were found suitable to characterize the response. In cases without GHD no correlation to age, sex and pubertal development was observed. A maximal GH level of above 10 ng/ml was found to be normal. In 3 out of 86 children without GHD (one with Turner syndrome; two with simple obesity) max GH fell short of 10 ng/ml, while 11 of 45 cases with GHD exceeded this margin. In GHD, max GH was inversely correlated with age. There was no difference in max GH between groups with or without perinatal pathology as a presumed cause of GHD. GH levels to GRF were positively correlated with maximal GH level during sleep in GHD, but not correlated with responses seen to insulin or arginine. The value of GRF testing for the confirmation of GHD is discussed in the light of other GH stimulatory tests and basal somatomedin C measurements. It is suggested that the combination of testing with GRF and the determination of a basal SmC level offers a safe and convenient way to diagnose GHD in clinically suspected cases, though in some cases further diagnostic tests may be needed. Dedicated to Professor A. M. Bongiovanni, M.D.     

Who is Treated with Growth Hormone Today?

ABSTRACT. The present demographic data from the Kabi International Growth Study (KIGS) database are summarized. Of the 2580 patients included, 85% have growth hormone deficiency (GHD) and 15% have other causes of growth failure. Idiopathic GHD is present in 78.5% of the patients, the remaining 21.5% have organic GHD. Isolated GHD is common in idiopathic GHD whereas multiple pituitary hormone deficiencies occur in at least 50% of the organic GHD patients. A preponderance of boys is observed in most groups of patients. Median chronological age (CA) at start of treatment is 10 years and median duration of therapy is 2.3 years. However, a wide range is observed. In most cases growth retardation is severe. In most patients with GHD height SDS for chronological age at start of therapy is at or below -3. The median difference between idiopathic and organic GHD is 1 SDS. Most patients have 6 or 7 injections of growth hormone (GH) per week. The median total weekly dose is approximately 0.5 IU/kg/week, but it is lower in older patients. It is concluded that steadily increasing numbers of patients with idiopathic and organic GHD are being treated with human GH (hGH). In addition, many patients with other growth disorders not necessarily associated with GHD receive hGH therapy. Chronological age at start of treatment still appears to be (too) high in most patients and growth retardation severe. The frequency of hGH injections has been increased to nearly daily administration. However, the total weekly dose appears to be low, especially in the older patients. It is hoped that KIGS will contribute to improving the efficacy of treatment and hence the quality of life for all patients with growth disorders.     

Growth hormone therapy in Silver Russell Syndrome: 5 years experience of the Australian and New Zealand Growth database (OZGROW)

Data were analysed on 33 children (22 males) with Silver Russell syndrome treated with growth hormone for periods up to 5 years. Baseline data (medians) at commencement of growth hormone (GH) therapy were age 6.7 years, bone age delay 1.7 years, height standard deviation score (SDS)-3.2, weight SDS –3.1, and growth velocity 5.7 cm/ year. All were prepubertal. Median birth weight SDS for gestational age was –3.2. GH was commenced at 14 IU/m² per week and subsequently adjusted according to response. Growth velocity and growth velocity SDS for chronological age (CA) improved over baseline and gains in height SDS for CA were 1.0, 1.5 and 1.8 SD over 3, 4 and 5 years respectively (P < 0.001). No significant increase in height SDS for bone age was observed. Increased GH doses were required after the 1st year to maintain growth rates. Mean bone age advancement was 3.1 years after 3 years of treatment, and 6.0 years after 5 years treatment. Younger age was a predictor of the growth response over the 1st year. Predictors of response after 3 years were catch-up growth, low weight SDS at birth and low height SDS for CA. Age at onset of puberty was normal, but height at onset of puberty was lower than normal means. Conclusion We have demonstrated significant improvement in growth in Silver Russell syndrome after 3 years of GH therapy, however data on estimated mature height and final height are insufficient to conclude final outcomes. Further follow up is required to assess the long-term benefit. Received: 19 July 1995 Accepted: 4 March 1996     

Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency

Seven children with growth hormone deficiency of hypothalamic origin responded to an i.v. bolus of growth hormone releasing hormone (GHRH) (1–29)-NH2 with a mean serum increase of 10.7 ng/ml growth hormone (GH) (range 2.5–29.3 ng/ml). Continuous s.c. administration of GHRH of 4–6 g/kg twice daily for at least 6 months did not improve the growth rate in five of the patients. One patient increased his growth rate from 1.9 to 3.8 cm/year and another from 3.5 to 8.2 cm/year; however, the growth rate of the latter patient then decreased to 5.4 cm/year. When treatment was changed to recombinant human growth hormone (rhGH) in a dose of 2 U/m² daily, given s.c. at bedtime, the growth rate improved in all patients to a mean of 8.5 cm/year (range: 6.2 to 14.6). Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.Abbreviations GH growth hormone - GHD growth hormone deficiency - GHRH growth hormone releasing hormone - hGH human growth hormone - rhGH recombinant human growth hormone - SM C/IGF I somatomedin C/insulin-like growth factor I On the occasion of the 85th birthday of Prof. Dr.Dr.h.c. mult. Adolf Butenandt     

Craniofacial and acral growth responses in growth hormone-deficient children treated with growth hormone

OBJECTIVES: To investigate the effects of growth hormone (GH) therapy on craniofacial growth and body proportions in growth hormone deficient children. STUDY DESIGN: By using a cross-sectional study design, we investigated GH effects on craniofacial growth with photographic facial morphometrics, head circumference, and hand and foot size in 52 children with GH deficiency (GHD) treated with GH (0.27 mg/kg/wk) for 0.19 to 15.5 years, compared with untreated children with GHD and normal first-degree relatives. To detect disproportion and to correct for stature, age and height age (HA) SD scores were analyzed. RESULTS: Untreated subjects with GHD had retarded facial height and width (P values=.001) compared with normal controls; small head circumference for age and HA (P=.001); small hands for age (P<.001) that were large for HA (P=.003); and small feet for age (P<.001) that were normal for HA. When compared with normal controls, GH-treated subjects had proportional facial heights but narrower facial widths. Head circumference, however, increased disproportionately to height (P=.001), becoming large for stature, and increasing with duration of therapy and cumulative GH dose (P<.001). Hands and feet grew proportionately to height. CONCLUSION: Growth hormone treatment with conventional doses partially corrects craniofacial deficits and does not adversely affect hand and foot growth but appears to result in excessive head circumference growth.     

Final height in Swedish children with idiopathic growth hormone deficiency enrolled in KIGS treated optimally with growth hormone

Aim: To assess final height in children with growth hormone deficiency (GHD) treated with human recombinant growth hormone (GH). Methods: Final height data for 401 Swedish children with idiopathic GHD and treated with GH, included in KIGS (Pfizer International Growth Database) between 1987 and spring 2006, were analysed retrospectively. Data were grouped according to sex, age and severity of GHD. Height at entry into KIGS, at the onset of puberty and near final height were analysed between groups. Results: Groups were heterogeneous for GHD, which ranged from partial to severe. For all groups, mean final height corrected for mid‐parental height was within the normal Swedish height range. In patients with severe GHD, mean final height was almost identical to mean normal Swedish height. About 16% of patients showed disproportionality (short legs) at final height and were significantly shorter than other patients. The parents of these children also demonstrated short stature. Conclusion: Children with idiopathic GHD receiving GH replacement therapy can achieve a final height that as a group is within the normal range and all achieve a height within their genetic potential.     

Growth Response in Prepubertal Children with Idiopathic Growth Hormone Deficiency During the First Two Years of Treatment with Human Growth Hormone. Analysis of the Kabi Pharmacia International Growth Study

From the large database of patients enrolled in the Kabi Pharmacia International Growth Study (KIGS), 289 prepubertal patients with idiopathic growth hormone deficiency (GHD), treated for 2 years with growth hormone (GH) substitution therapy, were selected. A multiple regression analysis was performed to determine both the auxological factors characterizing the patients at the beginning of the first and second years on GH therapy and the respective treatment modalities relevant to the magnitude of the growth response. It was observed that during the first year on GH therapy the magnitude of the growth response was negatively correlated with chronological age and height SDS, and positively correlated with target height SDS, GH dose (IU/kg/week) and frequency of GH injections. During the second year the growth response was negatively correlated with chronological age and the first-year GH dose (IU/kg/week), and positively correlated with height velocity during the first year, GH dose (second year), and injection frequency (second year). The data suggest that the forces of'catch-up'- auxologically entrenched within the distance between target height SDS and height SDS - no longer prevail during the second year of GH therapy. The inverse influence of the first-year GH dose in the two yearly phases of growth suggests that optimizing GH treatment must be attempted by analysing growth in response to GH over longer periods of time and considering that the growth process is influenced by interactive factors.     

Diagnostic value of growth hormone-releasing hormone test in children and adolescents with idiopathic growth hormone deficiency

Average growth hormone (GH) peaks following an i.v. growth hormone releasing hormone (GHRH) 1–29 stimulation test were significantly lower in 48 children and adolescents with GH deficiency (GHD) than in 20 age-matched controls (15.2+12.7 vs 37.5+28.1 ng/ml, 2P<0.001). Twelve patients exhibited a low GH peak (<5 ng/ml), 27 demonstrated a normal response (>10 ng/ml) and 9 showed an intermediate rise in plasma GH (5–10 ng/ml). Six of the 12 patients with low GH response to the first GHRH stimulation failed to respond to two other tests immediately before and after a 1 week priming with s.c. GHRH. These subjects with subnormal GH increase at repeat testing had total GHD (TGHD) and multiple pituitary hormone deficiency (MPHD) and had suffered from perinatal distress. On the contrary, 26 of 27 patients with normal GH response to the first test had isolated GHD and only a minority (8/27) had signs of perinatal distress. It is concluded that perinatal injuries primarily damage pituitary structures and that a pituitary defect more probably underlies more severe forms (TGHD and MPHD) of GHD.Presented in part at the 7th Meeting of the Italian Society for Paediatric Endocrinology (Milan, 20–21 October 1989)     

Effects of Short-Term Growth Hormone Therapy in Short Children without Growth Hormone Deficiency

ABSTRACT. Evaluation of 24-hour endogenous growth hormone (GH) secretion was carried out in 62 children, aged 7-16 years, who did not have classic GH deficiency (GHD). The mean 24-hour GH concentration, determined at 20-minute intervals over 24 hours, was variable, ranging from 1.28 to 11.39 μg/l with a mean of 4.95 ± 2.55 μl (± SD). There was a positive correlation between mean 24-hour GH concentration and plasma insulin-like growth factor I (IGF-I) values ( r = 0.54; p < 0.01). Recombinant human GH, 0.1 IU/kg/day was administered to 30 of the 62 children for 6 months followed by 6 months'observation without treatment. Thereafter, GH was administered at the same dose for a further 6 months to 16 children. The mean height velocities before, during, and after the first treatment period were 4.3 ± 0.9, 7.3 ± 1.9 and 4.9 ± 2.0 cm/year (mean ± SD), respectively. The height velocity during treatment was greater than pre- and post-treatment values ( p < 0.001). The height velocity Increased again during the second treatment period to a mean of 8.5 ± 2.0 cm/year ( p < 0.001). Nine other children were treated continuously in a similar manner for 1 year and their height velocity increased significantly from 4.1 ± 1.4 to 6.0 ± 1.9 cm/year ( p < 0.001). According to our criteria, 29 of the 39 children (74.4%) who were treated for 6-12 months showed a GH-dependent height increase during therapy. There were no differences between the children who responded to GH treatment and those who did not in terms of Chronological age, bone age, plasma IGF-I level, maximal GH level to insulin-induced hypoglycaemia, or mean 24-hour plasma GH concentration. These data indicate that some short children without GHD respond to GH treatment with an increased height velocity. Further investigations are required to determine the effect of GH on final height.     

The role of insulin like growth factor (IGF) — 1 and IGF — binding protein-3 in diagnosis of Growth Hormone Deficiency in short stature children

Objective  The purpose of this study was to evaluate the role of IGF-1 and IGFBP-3 in diagnosis of short stature children and adolescents in whom Growth Hormone Deficiency (GHD) was found. Methods  In this cross sectional study the referred short stature children and adolescents to Namazi Hospital in Shiraz- Iran, in 2003–2005 were studied. The inclusion criteria were proved short stature based on the physical examination, weight, height, standard deviation score (SDS) of height < −2, with considering stage of puberty and predicted height in children without any genetic or chronic disorders. The exclusion criteria were any positive physical or laboratory data suggesting hypothyroidism, rickets or liver disorders. For all patients a provocative growth hormone test was performed with propranolol and L-dopa and serum IGF-1 and IGFBP-3 were measured. GHD defined as peak(cutoff) serum GH level under 10 ìg/L and low IGF-1 and IGFBP-3 considered as cutoff serum level under −2 standard deviation. Results  Eighty one short stature patients (39 boys and 42 girls) with mean age of 10.6 ± 3.5 years completed the study. Seventeen patients with GHD were found and in 18 patients IGF-1 level were low. Only in 6 patients both GH and IGF-1 were low and 2 of them had low IGFBP-3. There were no correlations between the levels of GH,IGF-1 and IGFBP-3 in children with short stature due to GHD. The sensitivity and specifity of IGF-1 and IGFBP-3 in assessment of GHD were 35% and 81% for IGF-1 and 12% and 94% for IGFBP-3, respectively. Conclusion  No correlations were found between GH level and serum levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of those tests in assessment of GHD were poor.     

Multicentric study of efficacy and safety of growth hormone use in growth hormone deficient children in India

Growth Hormone being very expensive in India data on use of recombinant human growth hormone (rhGH) is scarce. The authors studied the effect and safety of one year of therapy with rhGH on growth velocity and predicted final height in Indian patients with growth hormone deficiency (GHD). A multicentric, prospective, open trial with rhGH was performed on 15 patients. Patients received rhGH in a dose of 0.7 IU (0.23 mg)/Kg/week. The mean pretreatment height was 111.2cms {SD 12.4}, height velocity was 3.1 cms per year {1.2} and predicted height was 146.5 cms {10.4} at a mean age of 12.0 (2.8). At the end of therapy mean height was 123.4 {11.9}, height velocity was 12.1 cms per year {2.8} and the predicted height was 153.0 cm {9.4}. The increase in predicted height was thus 6.5cm (4.2). The increment in height velocity with growth hormone therapy was statistically significant (p value= 0.001). The present study shows that children with growth hormone deficiency in India also benefit from therapy with rhGH even when treatment is started late as compared to the published Western data and there is a potential for increased final height.     

Central precocious puberty and growth hormone deficiency in a boy with Prader-Willi syndrome

In Prader-Willi syndrome (PWS) hypothalamic dysfunction is the cause of hormonal disturbances, such as growth hormone deficiency (GHD), hypogonadism, and delayed or incomplete puberty. Only a few cases of central precocious puberty (CPP) have been reported. We describe an 8.8-year-old PWS boy, with microdeletion of chromosome 15q, who developed CPP. On admission, height was 131.1 cm (+0.17 SD), BMI 26.2 kg/m², pubic hair (Ph) 2, and testis 4.5 ml. We found increased growth velocity (7 cm/year), high testosterone levels, pubertal response to GnRH test, and advanced bone age (10.6 years). An evaluation of growth hormone (GH) secretion revealed a deficiency. Pituitary MRI was normal. LHRH analogue therapy (Leuproreline 3.75 mg/28 days i.m.) was started at 8.9 years and discontinued at 11.3 years, when the patient had bone age of 13 years. During therapy, growth velocity, testosterone, FSH, and LH peak decreased significantly, with no pubertal progression. Growth hormone therapy (0.24 mg/kg/week) was started at 9.5 years and discontinued at 15.3 years because the patient had bone age of 17 years. After interrupting LHRH therapy the patient demonstrated spontaneous pubertal progression with pubertal gonadotropin and testosterone. At 16.3 years, height was 170 cm (−0.48 SDS), BMI 36.3 kg/m², Ph 4, testis volume 10 ml and there was a combined hypothalamic and peripheral hypogonadism hormonal pattern (normal LH even with low testosterone and undetectable inhibin B with high FSH). To our knowledge this is the fourth male patient with genetically-confirmed PWS demonstrating CPP and GHD and the first with a long follow-up to young adulthood.     

Growth hormone deficiency: a possible complication of glucose transporter 1 deficiency?

Glucose transporter 1 deficiency syndrome (GLUT1DS) is an autosomal dominant disorder of brain energy metabolism caused by impaired GLUT1-mediated glucose transport across the blood-brain barrier. Although the clinical spectrum of this disorder is expanding rapidly, the growth patterns and endocrine status of these patients are not well known. We report the case of a boy aged 12 years and 7 months who has GLUT1DS complicated by growth failure. His failure to grow had progressed since birth, and his body height was 125 cm (-3.6 SDS). Growth hormone stimulation tests showed severe growth hormone deficiency (GHD), and we initiated GH replacement therapy. After 2 years of treatment, the boy's growth rate recovered from 1.7 cm/year before treatment, to 7.5 cm/year and 4.3 cm/year after treatment with no adverse effects. We speculate that GHD is a possible complication of GLUT1DS and discuss the underlying causative mechanism. CONCLUSION: GHD may be a possible complication of GLUT1DS.     

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.     

Growth impairment and growth hormone therapy in children treated for malignant brain tumours

Eighty-two children with malignant brain tumours were treated according to the “8 in 1” chemotherapy protocol in Finland during 1986 to 1993. Thirty-seven with brain tumours not involving the hypothalamic-pituitary region are still alive and tumour-free. The growth and response to growth hormone (GH) therapy in these children was analysed. Children who received craniospinal irradiation had the most severe loss of height SDS, being −1.07 within 3 years of the diagnosis. Even children with no irradiation to the hypothalamic-pituitary axis had a mean change in height SDS of −0.5 after 3 years. Fifteen of 23 children who received craniospinal irradiation and two out of eight children who received cranial irradiation have received GH therapy. A catch-up growth response to the daily GH therapy with the mean dose of 0.7 IU/kg per week was complete in 3 years (+1.87 SDS), irrespective of craniospinal irradiation, in children who were treated at prepubertal age but was seen in none of the children who had reached pubertal age. Conclusion Growth impairment and GH deficiency are common in children treated for malignant brain tumours. The response to GH therapy is good in prepubertal children in terms of increased growth velocity, although the final height is not yet known. Received: 10 September 1996 and in revised form: 28 January 1997 / Accepted: 11 February 1997     

Growth Response in Prepubertal Children with Idiopathic Growth Hormone Deficiency during the First Year of Treatment with Human Growth Hormone. Analysis of the Kabi International Growth Study.

ABSTRACT. In order that children with growth hormone deficiency (GHD) reach the goal of normal adult stature, treatment modalities need to be optimized. From the large database of patients enrolled in the Kabi International Growth Study (KIGS), 257 prepubertal patients with idiopathic GHD undergoing their first year of growth hormone (GH) substitution therapy were selected. A multiple regression analysis was performed to determine both auxiological factors characterizing the patients and the factors related to the chosen treatment modalities which are of significance for the observed magnitude of the growth response. Due to the structure of the data, pretreatment height velocity and bone age-derived auxiological data were not considered. It was observed that the magnitude of the growth response was inversely correlated with chronological age and relative height (HT SDS) at the start of GH treatment but was positively correlated with mid-parental height. The growth response was also positively correlated with the GH dose (IU/kg/week) and the frequency of GH injections per week. A regression equation using these five parameters was derived, allowing the growth response of these patients to be predicted. The extension of this analytical approach in the future will allow the treatment of patients with GHD to be tailored to individual requirements.     

Effect of growth hormone therapy on bone metabolism of growth hormone deficient children

The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7girls, aged 3.7–13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5–0.7 IU/kg weekly, SC). Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO₄/GFR) were assessed. During therapy with hGH, a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO₄/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO₄/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. Conclusion GH treatment significantly influences mineral metabolism and the measurement of TPO₄/GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children. Received: 16 August 1996 / Accepted: 5 February 1997     

Small for gestation and growth hormone therapy

3 to 10% of neonates are born small for gestation (SGA). This usually occurs because of intrauterine growth retardation (IUGR). After birth most SGA infants show good catch-up growth and normalize their height and weight. About 10% of them continue to remain short (<−2SD) and do not achieve normal adult, height, resulting in psychosocial problems. The mechanism of short stature in these children is poorly understood. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. Diagnostic and management criteria for short stature in SGA were ill-defined in the past. Growth hormone (GH) therapy for improving height in these children has been approved by the FDA. GH therapy leads to growth acceleration and normalization of height during childhood. Long term GH treatment normalizes adult height above-2 SDS in 85% children, and 98% achieve an adult height within their target height range. GH therapy is safe in SGA children, but it is important to monitor for side effects.     

Rapid effect of intravenous growth hormone (GH)-releasing hormone 1–44 on plasma GH levels in children

Growth hormone releasing hormone (GHRH)-testing was performed in 24 short normal children (16 male, 8 female). Before and after administration of GHRH_1–44 (1g/kg body weight i.v.) blood samples for growth hormone (GH) determination were drawn at-30, 0, 1, 2, 3, 4, 6, 8, 10, 15, 30, 45, 60, and 90 min. Plasma GH increase was apparent 1 min after injection and in 12 patients (7 female) peak plasma GH values were reached within 15 min. In all patients plasma GH levels were greater than 10 ng/ml within the first 8 min following GHRH injection, but in 4 patients this level was not attained when considering only GH values obtained after 15 min. These results demonstrate the capability of the pituitary to rapidly secerete GH in response to GHRH_1–44 in children. Therefore, in this age group blood samples for GH determination should be taken earlier when testing with GHRH_1–44.Abbreviations GHRH growth hormone releasing hormone - GH growth hormone - SD standard deviation