Growth hormone treatment of short children born small-for-gestational-age: the Nordic Multicentre Trial

The aims of this study were to evaluate the efficacy and safety of different doses of growth hormone (GH) treatment in prepubertal short children born small-for-gestational-age (SGA). Forty-eight children born SGA from Sweden, Finland, Denmark and Norway were randomly allocated to three groups: a control group of 12 children received no treatment for 2 y, one group was treated with GH at 0.1 IU/kg/d (n = 16), and one group was treated with GH at 0.2 IU/kg/d (n = 20). In total 42 children completed 2 y of follow-up, and 24 children from the treated groups completed 3 y of treatment. Their mean (SD) age at the start of the study was 4.69 (1.61) y and their mean (SD) height was -3.16 (0.70) standard deviation scores (SDS). The children remained prepubertal during the course of the study. No catch-up growth was observed in the untreated group, but a clear dose-dependent growth response was found in the treated children. After the third year of treatment, the group receiving the higher dose of GH, achieved their target height. The major determinants of the growth response were the dose of GH used, the age at the start of treatment (the younger the child, the better the growth response) and the family-corrected individual height deficit (the higher the deficit, the better the growth response). Concentration of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 increased during treatment. An increase in insulin levels was found without negative effects on fasting glucose levels or glycosylated haemoglobin levels. GH treatment was well tolerated. In conclusion, short prepubertal children born SGA show a dose-dependent growth response to GH therapy, and their target height SDS can be achieved within 3 y of treatment given GH at 0.2 IU/kg/d. However, the long-term benefit of different regimens of GH treatment in children born SGA remains to be established.     

Growth response to growth hormone therapy following cranial irradiation

The growth response to growth hormone (GH) therapy has been studied in 12 children who received irradiation to the cranium alone either for brain gliomas, distant from the hypothalamic-pituitary axis, or as prophylaxis against CNS leukaemia. Seven children have completed GH treatment (mean duration 4 years) and five are presently on GH (mean duration 1.2 years). This response has been compared to that seen in 14 children with isolated idiopathic GH deficiency (IGHD), following GH therapy. Before treatment, the cranially irradiated patients (C-PRGHD) had higher standard deviation scores (SDS) for standing height, sitting height and leg length, and less bone age (BA) retardation, but started treatment at a similar age, and with a similar pre-treatment growth velocity and GH peak to standard provocative tests, compared to IGHD patients. GH produced a significant and similar increase in growth velocity (cm/year and SDS for BA) over the first 2 years' treatment in both groups. However C-PRGHD patients entered puberty and thus completed growth earlier than the IGHD group. As a result, cranially-irradiated children showed no change in height SDS with GH therapy, compared to catch-up growth in IGHD. Nevertheless, GH has enabled C-PRGHD patients to maintain their centile position and to achieve a more acceptable final height.Abbreviations GH growth hormone - IGHD idiopathic growth hormone deficiency - C-PRGHD post cranial-irradiation growth hormone deficiency - SDS standard deviation score - BA bone age - ALL acute lymphatic leukaemia - TSH thyroid stimulating hormone - CA chronological age - HA height age     

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.     

Growth hormone treatment in short children with chronic kidney disease

Growth hormone (GH) has been used for treatment of impaired growth in children with chronic kidney disease (CKD) for nearly 17 years. Controlled and open-label studies have shown that GH is highly effective in improving growth velocity and adult height. The growth response is negatively correlated with age and height at start and time spent on dialysis treatment; it is positively correlated with dose and duration of treatment and the primary renal disease (renal hypodysplasia). In children with renal transplants, corticosteroid treatment is an additional factor negatively influencing spontaneous growth rates. However, GH treatment is able to compensate corticosteroid-induced growth failure. GH treatment improved final height by 0.5-1.7 standard deviation score (SDS) in various studies, whereas the control group lost about 0.5 SDS in comparable time intervals. These variable results are explained in part by the factors mentioned above. The adverse events are comparable to those in non-CKD children treated with GH. CONCLUSION: GH treatment is safe and highly effective in improving growth and final height of short children with all stages of CKD. The highest treatment success is obtained if treatment is started at an early age and with relatively well-preserved residual renal function and continued until final height.     

One-year treatment with recombinant human growth hormone of children with meningomyelocele and growth hormone deficiency: a comparison of supine length and arm span.

Growth retardation and precocious puberty are frequently found in children with meningomyelocele (MMC). Lower limb contractions, spasticity and kyphoscoliosis may lead to disproportionate short stature. Most of these patients have structural brain defects or hydrocephalus which can cause growth hormone deficiency. In this study, 19 children aged between 3.5 and 12.8 years with MMC and growth hormone (GH) deficiency were treated with recombinant human GH for a period of 12 months. Supine length, arm span and growth velocity were compared before, and after 6 and 12 months of treatment with rhGH (daily dose 2.0 IU/m2 BSA s.c.). Mean supine length standard deviation score (SDS) increased by +0.8 SDS after 6 months and +1.2 SDS after 12 months of therapy. Mean arm span standard deviation score increased by +0.9 SDS and +1.3 SDS. Growth velocity increased in supine length from 3.3 cm/yr (-2.1 SDS) to 8.4 cm/yr (+2.4 SDS) and in arm span from 4.8 cm/yr (-1.3 SDS) to 8.6 cm/yr (+3.1 SDS) in the first 6 months and was 8.1 cm/yr (+2.4 SDS) and 8.3 cm/yr (+2.6 SDS) after 12 months of therapy. Linear correlation between SDS growth velocity supine length and SDS growth velocity arm span during one year of treatment was excellent (r = 0.65, p < 0.0025). We surmise that body proportions do not deteriorate when growth velocity is stimulated in MMC patients. Both supine length and arm span measurements are necessary to document growth in children with spinal dysraphism.     

The effect of human growth hormone therapy on skinfold thickness in growth hormone-deficient children

Skinfold thickness (ST) was measured in 43 children with various forms of growth hormone (GH) deficiency during the first year of GH therapy. The average (and SEM) initial ST, expressed as standard deviation score (SDS) was 1.17 (0.25) for subscapular, 0.63 (0.18) for triceps, and 0.40 (0.21) for biceps ST. During therapy the average decrease is 1 SD. Children in the pubertal age group and those with partial GH deficiency showed smaller decreases. A larger decrease of triceps ST was associated with lower GH and insulin peaks, and lower age, bone age and initial weight-for-height. Some correlations between ST decrease and growth response in the first year were significant, but still too low to allow of reliable predictions. The same was true for other clinical parameters. These data indicate that a chronic lack of GH leads to unequal fat distribution, possibly due to different sensitivities to GH in the trunk and extremities. The variability of ST responses to GH therapy limits clinical applications.Abbreviations GH growth hormone - hGH human growth hormone - SDS standard deviation score - SDS_BA standard deviation score for bone age - SDS_CA standard deviation score for chronological age - SEM standard error of the mean - ST skin fold thickness - ST-SDS skinfold thickness, expressed as a standard deviation score - ST-log skinfold thickness, expressed as 100.log₁₀ (reading in 0.1 mm-18) - TSH thyroid stimulating hormone     

No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short Children with GH Treatment

It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5 IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving significant adult height improvement in non-growth hormone deficient (non-GHD) short children. We compared the growth of GH-treated non-GHD short children with that of untreated short children to examine the effect of standard-dose GH treatment on non-GHD short children. GH treatment with recombinant human growth hormone (rhGH) was started before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at the Foundation for Growth Science who have now reached their adult height. In 119 untreated boys and 127 untreated girls whose height standard deviation score (SDS) was below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, in both sexes. Adult height and adult height SDS were significantly greater in the untreated group than in the GH-treated group, in both sexes, although the change in height SDS did not differ significantly. Height SDS was significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in the untreated group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group closely matched the height SDS before GH treatment in the GH-treated group were chosen for comparison. Height SDS did not differ significantly between the GH-treated group before GH treatment and the untreated group at the age of 6 yr, nor were there differences between these subgroups in adult height, adult height SDS, or height SDS change, in either sex. The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week are reported to be necessary to improve adult height in non-GHD short children. Currently, the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve adult height.     

Growth hormone replacement therapy in children with leukemia in remission

We describe a patient with leukemia in remission for 7 years who developed growth hormone (GH) deficiency and was treated with recombinant human growth hormone (rhGH). We compare her growth with that of patients from the National Cooperative Growth Study (NCGS) database, 145 with leukemia in remission and 725 with idiopathic growth hormone deficiency (IGHD) on treatment with rhGH. We also review the literature on the risk of relapse of leukemia in similar patients. The patients with leukemia in remission from the NCGS database had a significantly lower change of mean height standard deviation score than that of IGHD patients in the first, second, and third year of rhGH treatment. The relapse rate of leukemia in patients treated with rhGH is between 0.8% and 2%. Starting rhGH therapy in patients with leukemia in remission and with GH deficiency at an adequate dosage and without undue delay would improve their growth response. Such therapy does not appear to increase the risk of leukemia.     

Growth response to growth hormone therapy following craniospinal irradiation

Nineteen (12 male, 7 female) children, who have received craniospinal irradiation for the treatment of a brain tumour distant from the hypothalamic-pituitary axis, resulting in growth hormone (GH) deficiency (CS-PRGHD), have been treated with GH. Eight have completed growth. Comparison has been made with the growth of seven untreated children, whose heights and growth rates at presentation were normal despite GH deficiency secondary to irradiation. GH produced a significant increase in growth velocity over the first 3 years' treatment in CS-PRGHD patients with a mean first year increment of 3 cm/year. Patients, treated to completion of growth, showed a significant increase in leg length standard deviation (SD) score (SDS+0.2) compared to that of the untreated (SDS–0.9) (P<0.05). Stitting height SD scores decreased irrespective of GH therapy (by -1.7 for the treated and -2.2 for the untreated). The onset of puberty in the irradiated patients occurred at a mean bone age of 10.7 years in males and 9.9 years in females. This limited the time available for GH therapy. These factors resulted in a decrease in standing height SDS of 0.9 at completion of GH therapy in CS-PRGHD, but a decrease of 1.7 in those not treated with GH. Thus GH therapy failed to induce catch-up growth in irradiated patients, but it did prevent further loss of adult stature, with a mean final height SD score of -3.4 in CS-PRGHD patients.Abbreviations GH growth hormone - CS-PRGHD post craniospinal irradiation growth hormone deficiency - change in - SDS standard deviation score - ALL acute lymphatic leukaemia - IGHD isolated growth hormone deficiency - C-PRGHD post cranial irradiation growth hormone deficiency - FSH follicle stimulating hormone - LH luteinising hormone - BA bone age - TSH thyroid stimulating hormone - CA chronological age     

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.     

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.     

Final height in short children born small for gestational age treated with growth hormone

The aim of this observational study was to assess the long-term growth responses to GH treatment of children born small for gestational age (SGA). GH treatment was begun before puberty and continued to final height (FH). Seventy-seven short (height SD score below -2) prepubertal children born SGA (below -2 SD for birth weight and/or birth length), with a broad range of GH secretory capacity, were treated with GH in a daily dose of 33 microg/kg (0.1 U/kg), beginning before the onset of puberty. We observed a difference between adult and pretreatment projected height of 1.3 SD (9 cm) for the entire group. Among the children treated for >2 y before puberty, this mean gain (i.e. difference) in final height was 1.7 SD, whereas the mean gain was 0.9 SD among those in whom treatment was begun <2 y before puberty. Better catch-up growth was observed in the younger (r=-0.56, p<0.0001), shorter (r=-0.49, p<0.0001), and lighter (r=-0.46, p<0.0001) subjects. We conclude that GH treatment improves the final height of short children born SGA. The height gain attained before the onset of puberty is maintained to final height. The younger, shorter, and lighter the child at the start of GH treatment, the better the response. Moreover, most of these SGA individuals treated with GH reach their target height.     

Contribution of dose and frequency of administration to the therapeutic effect of growth hormone.

Forty two prepubertal children who were growth hormone insufficient were treated for the first time with 12 IU of biosynthetic methionyl growth hormone a week in three subcutaneous regimens for one year after one year of pretreatment observation. Thirteen received 4 IU growth hormone three days a week (group 1), 21 received 2 IU six days a week (group 2), and eight received 1 IU twice daily six days a week (group 3). The mean (SD) changes in height velocity standard deviation score (SDS) were +3.8 (1.7) in group 1, +5.3 (2.6) in group 2, and +5.9 (2.7) in group 3. There was a highly significant relation between the change in height velocity SDS and pretreatment height velocity SDS with a significant difference between the response of subjects receiving less than 15 IU/m2/week or greater than 15 IU/m2/week growth hormone. Age, bone age, height SDS, and height for bone age SDS did not contribute to the prediction of response during the first year of treatment. We recommend that growth hormone should be given in a dose of at least 15 IU/m2/week by equally divided daily subcutaneous injections.     

An overview of the GHMonitor, a registry of children treated with Saizen somatropin [recombinant hGH for injection

The GHMonitor, introduced in 1998, monitors demographics and outcomes in children treated with Saizen (somatropin [recombinant hGH for injection]). Follow-up data are available on 697 patients. The proportion of male to female patients receiving growth hormone (GH) treatment was 67:33. Severity of the height deficit present at enrollment varied by diagnosis with patients with Turner syndrome being shortest [height standard deviation score (SDS)=-3.7+/-1.7] and those with organic GH deficiency the least severely stunted (height SDS=-1.9+/-1.5). Forty-eight patients (6.9%) discontinued participation in the registry. The most common reason for discontinuing GH was completion of growth; the second was family relocation. There were 53 adverse events reported in 33 patients in 1977 patient-years of followup. Most were self-limited but 13 were serious, and 5 resulted in discontinuation of treatment. Data from The GHMonitor provide a real world glimpse of current North American GH treatment practices.     

The efficacy of grwoth hormone in different types of growth failure

One hundred and one children with GH deficiency, prenatal growth disorders, growth-retarding diseases, or normal variant short stature received GH for at least one year. Responders were observed in all groups. In the whole series of 72 prepubertal children the increments in height velocity showed negative correlations with the highest serum GH levels obtained in provocation tests.In the prepubertal children with normal growth potential the velocity SDSs during the first year of therapy showed positive correlations with initial ages and BAs, and negative correlations with height SDSs. In the 5 children with cartilage-hair hypoplasia the mean velocity increased from -1.9 to -0.6 SD. In the 8 children with Mulibrey nanism the mean velocity increased from -2.0 to 0.8 SD. The 4 children with various chromosome anomalies also showed an acceleration.The therapy brought about a significant increase in predicted final height only in the groups with normal growth potential. Final heights were known for 16 patients. Their heights were fairly accurately predicted by the RWT method, but the IPH method gave overpredictions. Both predictions showed strong correlations with the final heights.Additional low-dose androgen therapy in 10 boys, started at ages 9.5 to 18.9 years and after 1.4 to 4.7 years of GH therapy, accelerated growth without substantially affecting predicted height. The acceleration was mostly of the growth of sitting height.Abbreviations BA bone age - CHH cartilage-hair hypoplasia - GHD GH deficiency, GH deficient - iGHD isolated GHD - IPH index of potential height (height SDS for adjusted BA) adult height prediction method [23] - Maximal GH highest plasma GH level during an insulin or insulin-arginine test - MPHD multiple pituitary hormone deficiency - RWT the adult height prediction method of Roche, Wainer and Thissen [39] - SDS height standard deviation score - SDS SDS corrected for parental height     

Growth hormone therapy in Turner's syndrome. Impact of injection frequency and initial bone age.

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.     

Recombinant human growth hormone treatment in children with thalassemia major

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

Empty sella in short children with and without hypothalamic-pituitary abnormalities

A study was conducted on growth hormone (GH) response to oral clonidine (0.15 mg/m²), GH and cortisol responses to i.m. glucagon (0.1 mg/kg), and glucose response to an oral load of glucose (1.75 g/kg). Measurements were made on the circulating concentrations of free thyroxine (FT4), thyroid stimulating hormone (TSH) and different growth parameters and CT sellar images in 25 GH deficient children (Peak GH response to clonidine and glucagon<7 ug/ml), 15 growth retarded children (Ht<5th percentile for age and gender) with sickle cell disease (SCD) and GH deficiency, 30 randomly selected children with normal variant short stature (NVSS) (HtSDS 2SD below the mean for age and gender with normal GH response to stimulation (>10 ug/ml) and 20 age-matched normal children were evaluated. Out of the 25 children with GH deficiency, five had multiple pituitary hormonal deficiency (GH<TSH and/or ACTH. deficiencies), and 20 had isolated GH deficiency. Empty sella, either complete or partial, was detected in 9 out the 20 children with isolated GH deficiency (45%), 4 out of the 5 children with multiple pituitary deficiency (80%), all the children with SCD and GH deficiency (100%), 3 out of the 30 children with NVSS (10%) and in none of the normal children. The insulin-like growth factor-1 (IGF-I) concentrations were significantly lower in the two groups of children with GH deficiency compared to those with NVSS. The height standard deviation scores (HTSDS) were significantly lower and the annual growth velocity was slower in children with idiopathic GH deficiency and empty sella compared to those with NVSS and those with empty sella associated with SCD. The bone age delay (yr) did not differ among the 3 groups of children with short stature. All children with isolated GH deficiency associated with empty sella had normal body mass indices (BMI), while all the children with SCD and empty sella had BMI below the 5th percentile for the corresponding age and gender. None of the children had glucose intolerance. In conclusion, children with growth retardation and abnormal hypothalamic pituitary functions have high incidence of empty sella. However, empty sella is detected in considerable number (10%) of short children with normal hypothalamic pituitary function.     

Growth hormone (GH) provocation tests and the response to GH treatment in GH deficiency.

OBJECTIVE: To identify factors, particularly the growth hormone (GH) provocation test result, affecting growth response to GH treatment in children with GH deficiency (GHD). SUBJECTS: A total of 337 prepubertal GHD patients aged <10 years from the UK Pharmacia KIGS database (GH response to provocation test <20 mU/l). OUTCOME MEASURE: Annual change in height standard deviation score (SDS) (revised UK reference) in the first and second years of treatment. RESULTS: Height increased by 0.74 SDS units (SD 0.39) in the first year of treatment and 0.37 units (SD 0.27) in the second. Adjusting for age, height, weight, midparent height, and injection frequency, the strongest predictor of first year growth response was the GH provocation test result; halving the result predicted an extra height increment of 0.09 units (p<0.0001). It predicted the second year response less well (p<0.0002) and after adjusting for the first year response was not predictive at all. CONCLUSIONS: Among patients referred for possible GHD, the GH provocation test, though not a gold standard for diagnosis, is a valuable predictor of growth response in the first year of treatment. A year's treatment is recommended for cases with a marginal provocation test result, with the option to continue treatment if the response is adequate. The value of unified protocols for single or repeated provocation tests needs to be assessed.     

Carbohydrate metabolism on high dose growth hormone therapy in children treated for leukaemia

The effect on carbohydrate metabolism of a high dose growth hormone (GH) regimen (1.2 U/kg per week) was assessed on 24 children who had previously been treated for leukaemia. Sixteen patients received high dose GH and eight patients received a conventional dose of GH (0.6 U/kg per week). Oral glucose tolerance tests (OGTT) were performed at baseline and after 3 months of treatment with GH. For the entire group between 0 and 3 months, there was a significant increase in mean (and standard deviation) fasting plasma glucose (0.3 +/- 0.6 mmol/L), fasting insulin level (11 +/- 26 mU/L), and 2 h insulin level (20 +/- 40 mU/L). One patient, who received a conventional dose of GH, developed substantial carbohydrate intolerance. For the entire group, there was no change in response to a carbohydrate load at 3 months as measured by the area under the plasma glucose or insulin curve. There was no significant difference between conventional and high dose groups at 3 months as assessed by these parameters. This study demonstrates that a higher dose of GH may be used in these children in an attempt to improve their final height, without increased risk of carbohydrate intolerance in the short term.