| 1. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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| 2. |
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| 3. |
- Andersson, Björn, 1977, et al.
(författare)
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Decrease in adiponectin levels correlates to growth response in growth hormone-treated children.
- 2009
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Ingår i: Hormone research. - : S. Karger AG. - 1423-0046 .- 0301-0163. ; 71:4, s. 213-8
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin is secreted by adipose tissue and circulates in human plasma at high levels. Decreased adiponectin levels are associated with insulin resistance and obesity. The aim of this study was to investigate whether changes in serum adiponectin levels are related to the growth response, insulin levels and insulin resistance during growth hormone (GH) treatment.
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| 4. |
- Andersson, Björn, 1977, et al.
(författare)
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Proteins related to lipoprotein profile were identified using a pharmaco-proteomic approach as markers for growth response to growth hormone (GH) treatment in short prepubertal children
- 2009
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Ingår i: Proteome Science. - : Springer Science and Business Media LLC. - 1477-5956. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The broad range in growth observed in response to growth hormone (GH) treatment is mainly caused by individual variations in both GH secretion and GH sensitivity. Individual GH responsiveness can be estimated using evidence-based models that predict the response to GH treatment; however, these models can be improved. High-throughput proteomics techniques can be used to identify proteins that may potentially be used as variables in such models in order to improve their predictive ability. Previously we have reported that proteomic analyses can identify biomarkers that discriminate between short prepubertal children with idiopathic short stature (ISS) who show good or poor growth in response to GH treatment. In this study we used a pharmaco-proteomic approach to identify novel factors that correlate with the growth response to GH treatment in prepubertal children who are short due to GH deficiency or ISS. The study included 128 short prepubertal children receiving GH treatment, of whom 39 were GH-deficient and 89 had ISS. Serum protein expression profiles at study start and after 1 year of GH treatment were analyzed using SELDI-TOF. Cross-validated regression and random permutation analyses were performed to identify significant correlations between protein expression patterns and the 2-year growth response to GH treatment. RESULTS: At start of treatment we identified a combination of seven protein peaks that correlated with the 2-year growth response in the GH-deficient group (R2 = 0.73). After 1 year of treatment, a combination of four peaks in the GH-deficient group (R2 = 0.64), eight peaks in the ISS group R2 = 0.47) and eight peaks in the total study group correlated with the 2-year growth response R2 = 0.38).The peaks identified corresponded to apolipoproteins A-I, A-II, C-I, C-III, transthyretin and serum amyloid A 4, which are all part of the high-density lipoprotein. CONCLUSION: Using a proteomic approach we identified biomarkers related to the lipoprotein profile that could be used to predict growth response to GH treatment in prepubertal children who are short as a result of GH-deficiency or who have ISS.These results support our previous findings that apolipoproteins and transthyretin may have a role in GH sensitivity.
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| 5. |
- Andersson-Wallgren, Gunnel, et al.
(författare)
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Growth Promoting Treatment Normalizes Speech Frequency in Turner Syndrome
- 2008
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Ingår i: Laryngoscope. - 0023-852X. ; 118:6, s. 1125-1130
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: To assess objective and subjective voice parameters among Turner syndrome (TS) women in relation to genotype, hearing, growth, and previous treatment with growth hormone (GH) and androgen given that lowering of speaking fundamental frequency (SFF) during treatment is regarded as a negative side effect. STUDY DESIGN:: Cross-sectional, controlled for karyotype and age. METHODS:: Voice function was studied objectively (SFF) and subjectively (questionnaire) in 117 women with TS. RESULTS:: SFF did not differ between treated and nontreated participants or between patients with a spontaneous versus induced puberty. SFF was dependent on karyotype but not age. Subjective voice change was reported four times more often among treated compared with nontreated TS women (odds ratio [OR] = 4.4; 95% confidence interval [CI]: 0.9-20.10), whereas voice and articulation problems were reported three times more often among untreated compared with treated cases (OR = 2.9; 95% CI: 1.0-8.3). Voice symptoms were over-represented among patients having micrognathia (OR = 6.0; 95% CI: 1.6-22.3), hearing loss (OR = 8.6; 95% CI: 1.7-43.1), and monosomy (OR = 6.2; 95% CI: 0.8-36.2) but not among those with an arched palate. CONCLUSIONS:: When given to TS girls, GH (33-66 mug/kg/d) and androgen (0.05 mg/kg/d) normalized SFF and reduced voice and articulation problems in adulthood. The TS phenotype includes important voice and speech problems, which in turn are associated with hearing problems, although genotypic, monosomic, and isochromosome patients have more voice problems and also more high-pitched voices than mosaic patients. Most TS women, despite their karyotype or age, exhibit a higher frequency of pitched voice than non-TS women.
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| 6. |
- Boguszewski, M. C., et al.
(författare)
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Insulin-like growth factor-1, leptin, body composition, and clinical status interactions in children with cystic fibrosis
- 2007
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Ingår i: Horm Res. - : S. Karger AG. - 0301-0163. ; 67:5, s. 250-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Children with cystic fibrosis (CF) are of increased risk of reduced fat body mass (FBM) and lean body mass (LBM). Serum concentrations of insulin-like growth factor-1 (IGF-1)and leptin could be markers of LBM and/or FBM depletion. To evaluate the relationships between disease activity, body composition, IGF-1 and leptin concentrations in CF children. METHODS: A cross-sectional study with 26 CF children aged 5.0-15.5 years and 33 healthy controls, mean age 9.4 years. Body composition was evaluated by dual-energy X-ray absorptiometry. Fasting blood samples were analyzed for leptin, IGF-1 and IGFBP-3. RESULTS: FBM standard deviation score (SDS; CF boys -0.02 +/- 0.88 vs. 0.78 +/- 0.65, p < 0.01; CF girls -0.37 +/- 1.15 vs. 0.70 +/- 0.97, p < 0.05), leptin concentration (CF boys 2.07 +/- 0.79 vs. 3.07 +/- 1.28 ng/ml, p < 0.05; CF girls 2.71 +/- 0.86 vs. 5.00 +/- 2.95 ng/ml, p < 0.05) and IGF-1SDS (CF boys -1.43 +/- 1.50 vs. -0.32 +/- 0.88, p < 0.05; CF girls -0.66 +/- 1.66 vs. 0.64 +/- 0.57, p < 0.01) were lower in CF children compared to controls. Shwachman score was the strongest predictor of lean body mass (R = 0.63). Leptin levels explain 60% of the variability in FBM. CONCLUSION: Serum concentrations of IGF-1 and leptin are decreased in children with CF and are associated with clinical conditions and body composition.
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| 7. |
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| 8. |
- Craig, M. E., et al.
(författare)
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Growth hormone treatment and adverse events in Prader-Willi syndrome: data from KIGS (the Pfizer International Growth Database)
- 2006
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Ingår i: Clin Endocrinol (Oxf). ; 65:2, s. 178-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the response to recombinant GH treatment and adverse events in children with Prader-Willi syndrome (PWS) from KIGS, the Pfizer International Growth Database. PATIENTS: A total of 328 children (274 prepubertal, median age 6.0 years; 54 pubertal, median age 12.7 years) were treated for 1 year and 161 children were treated for 2 years with GH. RESULTS: Height standard deviation score (SDS) increased significantly during treatment; the response was greater in prepubertal (-0.7 vs.-1.8 pretreatment) compared with pubertal children (-1.5 vs.-1.8). Predictors of first-year height velocity in multiple regression analysis were GH dose, body weight (positively correlated), height SDS minus mid-parental height SDS and chronological age (negatively correlated), together accounting for 39% of the variation in response to GH. Body mass index (BMI) SDS did not change significantly during 2 years of treatment. Of all the 675 GH-treated PWS patients in KIGS, there were five cases of sudden death (age range 3-15 years). Three were obese (weight for height > 200%) and causes of death included bronchopneumonia, respiratory insufficiency and sleep apnoea. Scoliosis was the most commonly reported adverse event (n = 24), four children developed hyperglycaemia and six had presumptive diabetes (type 2 in five, and one case of type 1). CONCLUSIONS: Short-term growth improved in response to conventional doses of GH in children with PWS. Prior to commencement of GH, examination of the upper airways and sleep studies should be performed in PWS patients. GH should be used with caution in those with extreme obesity or disordered breathing and all patients should be closely monitored for adverse events.
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| 9. |
- Dahlgren, Jovanna, 1964, et al.
(författare)
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Final height in short children born small for gestational age treated with growth hormone
- 2005
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Ingår i: Pediatr Res. ; 57:2, s. 216-22
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Dahlgren, Jovanna, 1964, et al.
(författare)
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Models predicting the growth response to growth hormone treatment in short children independent of GH status, birth size and gestational age
- 2007
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Ingår i: BMC Med Inform Decis Mak. - : Springer Science and Business Media LLC. - 1472-6947. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mathematical models can be used to predict individual growth responses to growth hormone (GH) therapy. The aim of this study was to construct and validate high-precision models to predict the growth response to GH treatment of short children, independent of their GH status, birth size and gestational age. As the GH doses are included, these models can be used to individualize treatment. METHODS: Growth data from 415 short prepubertal children were used to construct models for predicting the growth response during the first years of GH therapy. The performance of the models was validated with data from a separate cohort of 112 children using the same inclusion criteria. RESULTS: Using only auxological data, the model had a standard error of the residuals (SDres), of 0.23 SDS. The model was improved when endocrine data (GHmax profile, IGF-I and leptin) collected before starting GH treatment were included. Inclusion of these data resulted in a decrease of the SDres to 0.15 SDS (corresponding to 1.1 cm in a 3-year-old child and 1.6 cm in a 7-year old). Validation of these models with a separate cohort, showed similar SDres for both types of models. Preterm children were not included in the Model group, but predictions for this group were within the expected range. CONCLUSION: These prediction models can with high accuracy be used to identify short children who will benefit from GH treatment. They are clinically useful as they are constructed using data from short children with a broad range of GH secretory status, birth size and gestational age.
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| 11. |
- Darendeliler, F., et al.
(författare)
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Bone Age Progression during the First Year of Growth Hormone Therapy in Pre-Pubertal Children with Idiopathic Growth Hormone Deficiency, Turner Syndrome or Idiopathic Short Stature, and in Short Children Born Small for Gestational Age: Analysis of Data from KIGS (Pfizer International Growth Database)
- 2005
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Ingår i: Horm Res. ; 63:1, s. 40-7
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The beneficial effects of growth hormone (GH) therapy on statural growth in children are well established, but the effects on skeletal maturation are less clear. The progression of bone age (BA) was therefore studied during the first year of GH treatment in pre-pubertal children with idiopathic GH deficiency (GHD), Turner syndrome (TS) or idiopathic short stature (ISS), and in short pre-pubertal children born small for gestational age (SGA). Methods: Cross-sectional data on 2,209 short children with idiopathic GHD, 694 with TS, 569 with ISS and 153 with SGA were analysed. Longitudinal data were also analysed from 308 children with idiopathic GHD, 99 with TS, 57 with ISS and 29 with SGA. All patients included in the study were enrolled in KIGS (Pfizer International Growth Database) and were being treated with recombinant human GH (Genotropin((R))). BA was assessed using the Greulich and Pyle method at baseline and after 1 year of GH therapy. Results: In all groups of patients the mean progression of BA was 1 year during the year of GH therapy, although there was considerable individual variation. Progression of BA was not correlated with chronological age, BA, height SD score (SDS) or body mass index SDS at the onset of GH therapy. There was also no consistent effect of the GH dose on BA progression. Conclusion: Progression of BA appears to be normal in patients receiving GH in these diagnostic groups, at least over the first year of treatment in pre-puberty. Copyright (c) 2005 S. Karger AG, Basel.
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| 12. |
- Darendeliler, Feyza, et al.
(författare)
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Recurrence of brain tumours in patients treated with growth hormone: Analysis of KIGS (Pfizer International Growth Database)
- 2006
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Ingår i: ACTA PAEDIATRICA. - : Wiley. - 0803-5253. ; 95:10, s. 1284-1290
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth hormone (GH) has been used successfully in the treatment of short stature secondary to GH deficiency in survivors of childhood brain tumours. There has been concern that GH might increase the risk of recurrence. AIM: To analyse KIGS (Pfizer International Growth Database) with respect to tumour recurrence in patients with brain tumours. METHODS: Data for tumour recurrence were analysed retrospectively in 1038 patients with craniopharyngiomas, 655 with medulloblastomas, 113 with ependymomas, 297 with germinomas, and 400 with astrocytomas or gliomas. All patients had received recombinant human GH (Genotropin, Pfizer Inc.). RESULTS: Recurrence-free survival rates were 63% at a follow-up of 10.3 y in craniopharyngioma, 69% in 9.1 y in the glial tumours, 71% in 7.4 y in germinomas, 92% in 4.6 y in medulloblastomas and 89% in 2.5 y in ependymomas. Dose of GH and treatment modalities did not differ significantly between patients with and without recurrence. CONCLUSION: Tumour recurrence rates in surviving patients with brain tumours receiving GH treatment do not appear to be increased compared with published reports. However, longer follow-up regarding recurrences and secondary neoplasms remains essential.
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| 13. |
- Decker, Ralph, 1968, et al.
(författare)
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Different thresholds of metabolic GH effects in prepubertal children
- 2009
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Ingår i: Hormone Research.
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Konferensbidrag (refereegranskat)abstract
- Context: In addition to growth hormone (GH) effects to promote linear growth in children, GH also has substantial effects on insulin sensitivity, lipolysis, lipids, and body composition. A dissociation between anabolic and lipolytic GH effects has been suggested. Objective: The objective of the present study was to further investigate dissociated GH effects by calculating the GH doses to attain half of a given metabolic effect, the effective dose 50% (ED50%). Hypothesis: The hypothesis was that there are dose-dependent thresholds in different variables reflecting metabolism. Design: A randomized, prospective, multicentre trial was performed for a 2 years period, with two treatment regimens in short prepubertal GHD and ISS children a) individualized GH dose with six different dose groups ranging 17-100 g/kg/day (n=87) and b) fixed GH dose of 43 g/kg/day (n=41). Results: Contrary to changes in fat mass, leptin, lipids and skinfold measurements, there was evidence for different thresholds in metabolic variables for a given GH dose when performing ANOVA, p<0.001. was calculated as the difference between 2 years and start of GH treatment. Besides height (SDS), growth related variables like weight SDS and BMI (kg/m ); measures of body composition such as fat-free mass (FFM) (kg), FFM index (FFMI) (kg/m ), waist (cm), hip (cm); as well as biochemical markers like IGF-1 (SDS), IGFBP-3 (SDS); insulin (mU/L) showed dose-dependency with different ED50% levels. Conclusions: Differences of the ED50% on metabolic variables were seen in-between different GH dose spans. Thus we propose that there are different thresholds in GH effects on variables reflecting different metabolic aspects, suggesting muscle tissue being more sensitive than linear growth, GH induced insulin resistance, the rise in IGF-1 and the increase in hip circumference as a measure of 3-dimensional body growth.
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| 14. |
- Decker, Ralph, 1968, et al.
(författare)
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Individualized GH treatment gives improved growth but not higher insulin nor IGF1 compared to standard GH dose after 2 years of catch-up growth
- 2007
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Ingår i: Hormone Research. - 3805583273 ; 68:Supplement Issue 1
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Konferensbidrag (refereegranskat)abstract
- Weight-based approaches for ‘standard’ GH dosing result in dramatic variability in height outcome and IGF-1 levels. In a recent study we showed that growth response variability can be reduced by individualized GH dosing guided by the individual responsiveness estimated by our prediction model. The hypothesis was that despite many individuals needed higher GH doses, the individualized GH regimen would not give higher levels of metabolic variables compared to the group of children receiving standard treatment. We performed an open, prospective, randomized, multicentre trial in 128 prepubertal short children diagnosed as GHD or ISS, for a 2 yr catch-up growth period, with two treatment regimens providing the same mean GH dose a) individualized GH dose, ranging 17-100 µg/kg/day (n=87) and b) standard GH dose: 43 µg/kg/day (n=41). The set goal for treatment effect was to reach midparental height (MPH) SDS after 2 yrs of GH treatment. This goal was reached for a higher proportion of children treated with the individualized dose (p<0.01). Despite this there were no differences between the individual and the standard dose group concerning the mean and variances of Δinsulin, Δleptin, ΔIGF1(SDS), ΔIGF-BP3(SDS) and ΔIGF1/IGF-BP3(SDS). Δ is calculated as the difference between the value at 2 yrs and at the start of treatment. Moreover there were no differences between the groups regarding the mean or the range of these variables at 2 yrs of treatment. It can be concluded that despite a much broader range in GH dose, which comprised a maximum dose of more than 200% of the standard dose, the variability of the metabolic parameters during treatment within the groups and the absolute levels reached at 2 yrs were the same in the two groups. In fact a better growth response in relation to MPH(SDS) was achieved without a difference in metabolic variables between the groups. Individual dosing is preferable in GH treatment.
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| 15. |
- Decker, Ralph, 1968, et al.
(författare)
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Lipolytic and anabolic effects of GH are dissociated during individualized GH treatment
- 2008
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Ingår i: European Society for Paediatric Endocrinology. - 9783805586207 ; 70:Supplement Issue 1
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Konferensbidrag (refereegranskat)abstract
- Context: There is a broad variation in longitudinal growth response during GH treatment among prepubertal children. Yet, growth is but one of the several effects of GH. Our working hypothesis was a dissociation of anabolic and lipolytic effects of GH. Objective: To investigate whether diverse metabolic functions respond analogical to growth. Design: A randomized, prospective, multicentre trial was performed, for a 2 years period, with two treatment regimens providing the same mean GH dose a) individualized GH dose, six different dose groups ranging 17-100 µg/kg/day (n=87) and b) standard GH dose: 43 µg/kg/day (n=41). Patients: 128 prepubertal short children, 75% of them diagnosed as GH deficient and 25% as idiopathic short stature. Main Outcome Measures: Changes in metabolic variables (delta 2 years - start). Results: Changes in IGF-1 correlated to height gain (r=0.54, p<0.0001). Stepwise regression showed that 71% of the variation in IGF-1 was explained by height gain (49%), chnages in insulin (9%), free fat mass (FFM) (5%), and biceps skinfold (4%), as well as GH dose (4%). Changes in IGF-1 solely accounted for all changes in FFM (31%). In contrast to total fat mass, changes in FFM were significantly higher after 2 years of GH doses above 40 µg/kg/day (p<0.001 Mann-Whitney test). In principle component analysis it can be demonstrated that the anabolic variables IGF-1, IGFBP-3, FFM, and insulin target in the same direction as height gain. All variables in this vector bundle show high reciprocal partial regressions. The anabolic component is dose-dependent. Variables derived from adipose tissue (total fat mass, leptin, skin fold measurements, triglycerides) and lipid metabolism (cholesterol, HDL, LDL, triglycerides, lipoprotein(a), apolipoprotein A-II) form up a lipolytic bundle. This is unrelated to the anabolic component and dose-independent. Conclusions: This study suggests that lipolytic and anabolic effects of GH are dissociated. The threshold of GH's lipolytic effects is much lower than its anabolic and growth effects.
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| 16. |
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| 17. |
- Engström, Eva, et al.
(författare)
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The role of maternal factors, postnatal nutrition, weight gain, and gender in regulation of serum IGF-I among preterm infants
- 2005
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Ingår i: Pediatr Res. ; 57:4, s. 605-10
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Tidskriftsartikel (refereegranskat)abstract
- IGF-I is important for somatic growth and development of the human fetus and neonate. IGF-I also plays an important role in normal vascularization of human retina, as it has been suggested that insufficient IGF-I may be a factor in the development of retinopathy of prematurity. The principal regulator of the bioavailability of IGF-I in the circulation is IGF binding protein 3 (IGFBP-3). The aim of this study was to study factors associated with postnatal serum concentrations of IGF-I and of IGFBP-3 in preterm infants from birth to an age corresponding to 40 wk postmenstruation. We conducted a prospective, longitudinal study in which we measured serum IGF-I and IGFBP-3 concentrations in 76 preterm infants from birth (postmenstrual ages 23-32 wk) until discharge from hospital around 40 wk. Information regarding nutrition, weight gain, maternal factors, and treatment with corticosteroids were collected weekly. Variables found to be associated with postnatal change over time of serum IGF-I and IGFBP-3 were postmenstrual age (p<0.001), weight gain (standard deviation score) (p<0.001), and enteral intake of protein (p<0.001). Male gender was associated with lower IGF-I levels (p<0.001). The relationship between protein intake and IGF-I (and also between protein intake and IGFBP-3) was positive, as was the relationship between weight gain and IGF-I (and between weight gain and IGFBP-3). These results indicate that the degree of prematurity, low enteral protein intake, male gender, and slow weight gain are associated with a slower postnatal increase of IGF-I in preterm infants.
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| 18. |
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| 19. |
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| 20. |
- Hellgren, Gunnel, 1961, et al.
(författare)
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A proteomic approach identified growth hormone dependent nutrition markers in children with idiopathic short stature
- 2008
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Ingår i: Proteome Science. - : Springer Science and Business Media LLC. - 1477-5956. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: The broad range in growth observed in short prepubertal children receiving the same growth hormone (GH) dose is due to individual variation in GH responsiveness. This study used a pharmaco-proteomic approach in order to identify novel biomarkers that discriminate between short non-GH-deficient (GHD) children who show a good or poor growth response to GH treatment. A group of 32 prepubertal children with idiopathic short stature (ISS) were included in the study. Children were classified on the basis of their first year growth velocity as either good (high responders, n = 13; range, 0.9-1.3 standard deviation score (SDS) or poor (low responders, n = 19; range, 0.3-0.5 SDS) responders to GH treatment (33 microg/kg daily). Serum protein expression profiles before, and after 1 year of GH treatment, were analyzed on a weak cationic exchange array (CM10) using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS). RESULTS: Changes in the intensity of two protein peaks (13.788 kDa and 17.139 kD) during the study period allowed the correct classification of 82% of children as high and low responders, respectively. The 13.788 kD peak, transthyretin, decreased in the high-responder group and increased in the low-responder group during 1 year of GH treatment, whereas the 17.139 kDa peak, apolipoprotein A-II (Apo A-II) decreased in the high-responder group and remained unchanged in the low-responder group. These peaks were identified by the consistency of peak pattern in the spectra, serum depletion experiments using specific antibodies and mass spectrometry. CONCLUSION: Our results suggest that transthyretin and apolipoprotein A-II may have a role in GH sensitivity and could be used as markers to predict which short prepubertal children with ISS will show a good or poor response to GH treatment.
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| 21. |
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| 22. |
- Hochberg, Z., et al.
(författare)
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Evo-devo of infantile and childhood growth
- 2008
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Ingår i: Pediatric Research. - 0031-3998. ; 64:1, s. 2-7
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Tidskriftsartikel (refereegranskat)abstract
- Human size is a tradeoff between the evolutionary advantages and disadvantages of being small or big. We now propose that adult size is determined to an important extent during transition from infancy to childhood. This transition is marked by a growth spurt. A delay in the transition has a lifelong impact on stature and is responsible for 44% of children with short stature in developed countries and many more in developing countries. Here, we present the data and theory of an evolutionary adaptive strategy of plasticity in the timing of transition from infancy into childhood to match the prevailing energy supply. We propose that humans have evolved to withstand energy crises by decreasing their body size, and that evolutionary short-term adaptations to energy crises trigger a predictive adaptive response that modify the transition into childhood, culminating in short stature.
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| 23. |
- Kjellberg, Heidrun, 1953, et al.
(författare)
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A longitudinal study of craniofacial growth in idiopathic short stature and growth hormone-deficient boys treated with growth hormone.
- 2007
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Ingår i: European journal of orthodontics. - : Oxford University Press (OUP). - 0141-5387 .- 1460-2210. ; 29:3, s. 243-50
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this prospective, longitudinal, controlled study is to describe the long-term safety and efficacy of growth hormone (GH) administration on craniofacial morphology in boys with short stature. Forty-six boys, who started GH treatment at the Department of Paediatrics G?teborg Paediatric Growth Research Centre, were consecutively included in the study. Twenty-five boys were classified as growth hormone-deficient (GHD) and 21 as idiopathic short stature (ISS). The patients were injected with 33 (n=31) or 67 (n=15) microg GH/kg body weight/day. The mean age at the start of treatment was 11.8 years [standard deviation (SD) 1.7]. To assess craniofacial growth, standard lateral cephalometric radiographs were obtained at the start of GH treatment, annually during 4 years, and at the end of GH treatment or when growth was less than 1 cm/year. The mean follow-up period was 6.4 years (SD 1.4). Growth changes were compared with boys from a semi-longitudinal reference group of 130 healthy subjects, 7-21 years of age. t-tests for independent and paired samples and multiple regression analysis were applied. Age- and gender-specific standard deviation scores for the cephalometric variables were calculated. Repeated measures analysis of variance was used to identify significant covariates over time, such as low/high GH dose and GHD/ISS and orthodontic treatment. During the study period, eight (out of 40) boys were treated with fixed orthodontic appliances, three with functional appliances (activators), and three with other appliances (plates and lingual arches). During GH treatment period, an overall enhancement in growth of the facial skeleton was observed in boys with short stature. The changes induced by GH yielded a more prognathic growth pattern, a more anterior position of the jaws in relation to the cranial base, and increased anterior rotation of the mandible. The mandibular corpus length and anterior face height of the GH-treated boys were greater at the end of the study compared with the boys in the reference group. No differences in growth response were noted either between the GHD and ISS boys or between those treated with either 33 (low dose) or 67 (high dose) microg GH/kg body weight/day. The only change that remained significantly correlated with orthodontic treatment was the alteration in mandibular ramus height, showing a larger change in the boys who had not undergone orthodontic therapy. The findings of this study demonstrate that GH treatment has a favourable influence on the craniofacial growth pattern of boys with short stature without acromegalic features.
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| 24. |
- Kriström, Berit, et al.
(författare)
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Growth hormone (GH) dosing during catch-up growth guided by individual responsiveness decreases growth response variability in prepubertal children with GH deficiency or idiopathic short stature
- 2009
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:2, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Weight-based GH dosing results in a wide variation in growth response in children with GH deficiency (GHD) or idiopathic short stature (ISS). OBJECTIVE: The hypothesis tested was whether individualized GH doses, based on variation in GH responsiveness estimated by a prediction model, reduced variability in growth response around a set height target compared with a standardized weight-based dose. SETTING: A total of 153 short prepubertal children diagnosed with isolated GHD or ISS (n = 43) and at least 1 SD score (SDS) below midparental height SDS (MPH(SDS)) were included in this 2-yr multicenter study. INTERVENTION: The children were randomized to either a standard (43 microg/kg.d) or individualized (17-100 microg/kg.d) GH dose. MAIN OUTCOME MEASURE: We measured the deviation of height(SDS) from individual MPH(SDS) (diffMPH(SDS)). The primary endpoint was the difference in the range of diffMPH(SDS) between the two groups. RESULTS: The diffMPH(SDS) range was reduced by 32% in the individualized-dose group relative to the standard-dose group (P < 0.003), whereas the mean diffMPH(SDS) was equal: -0.42 +/- 0.46 and -0.48 +/- 0.67, respectively. Gain in height(SDS) 0-2 yr was equal for the GH-deficient and ISS groups: 1.31 +/- 0.47 and 1.36 +/- 0.47, respectively, when ISS was classified on the basis of maximum GH peak on the arginine-insulin tolerance test or 24-h profile. CONCLUSION: Individualized GH doses during catch-up growth significantly reduce the proportion of unexpectedly good and poor responders around a predefined individual growth target and result in equal growth responses in children with GHD and ISS.
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| 25. |
- Kriström, Berit, et al.
(författare)
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The first-year growth response to growth hormone treatment predicts the long-term prepubertal growth response in children.
- 2009
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Ingår i: BMC medical informatics and decision making. - : Springer Science and Business Media LLC. - 1472-6947. ; 9, s. 1-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pretreatment auxological variables, such as birth size and parental heights, are important predictors of the growth response to GH treatment. For children with missing pretreatment data, published prediction models cannot be used. The objective was to construct and validate a prediction model for children with missing background data based on the observed first-year growth response to GH. The accuracy and reliability of the model should be comparable with our previously published prediction model relying on pretreatment data. The design used was mathematical curve fitting on observed growth response data from children treated with a GH dose of 33 microg/kg/d. METHODS: Growth response data from 162 prepubertal children born at term were used to construct the model; the group comprised of 19% girls, 80% GH-deficient and 23% born SGA. For validation, data from 205 other children fulfilling the same inclusion and treatment criteria as the model group were used. The model was also tested on data from children born prematurely, children from other continents and children receiving a GH dose of 67 microg/kg/d. RESULTS: The GH response curve was similar for all children, but with an individual amplitude. The curve SD score depends on an individual factor combining the effect of dose and growth, the 'Response Score', and time on treatment, making prediction possible when the first-year growth response is known. The prediction interval (+/- 2 SD res) was +/- 0.34 SDS for the second treatment year growth response, corresponding to +/- 1.2 cm for a 3-year-old child and +/- 1.8 cm for a 7-year-old child. For the 1-4-year prediction, the SD res was 0.13 SDS/year and for the 1-7-year prediction it was 0.57 SDS (i.e. < 0.1 SDS/year). CONCLUSION: The model based on the observed first-year growth response on GH is valid worldwide for the prediction of up to 7 years of prepubertal growth in children with GHD/ISS, born AGA/SGA and born preterm/term, and can be used as an aid in medical decision making.
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