| 1. |
- Craig, M. E., et al.
(författare)
-
Growth hormone treatment and adverse events in Prader-Willi syndrome: data from KIGS (the Pfizer International Growth Database)
- 2006
-
Ingår i: Clin Endocrinol (Oxf). ; 65:2, s. 178-85
-
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.
|
|
| 2. |
- Ranke, M. B., et al.
(författare)
-
Major determinants of height development in Turner syndrome (TS) patients treated with GH: analysis of 987 patients from KIGS
- 2007
-
Ingår i: Pediatr Res. - : Springer Science and Business Media LLC. - 0031-3998. ; 61:1, s. 105-10
-
Tidskriftsartikel (refereegranskat)abstract
- Little is known about factors determining height outcome during GH treatment in Turner syndrome (TS). We investigated 987 TS children within the Kabi International Growth Study (KIGS) who had reached near adult height (NAH) after >4 y GH treatment (including >1 y before puberty). Through multiple regression analysis we developed a model for NAH and total gain. Our results were as follows (median): 1) At start, age 9.7 yrs, height (HT) 118.0 cm (0.0 TS SDS), projected adult height 146.1 cm, GH dose 0.27 mg/kg wk; 2) NAH HT 151.0 cm (1.5 TS SDS); 3) Prepubertal gain 21.2 cm (1.6 TS SDS); 4) Pubertal gain 9.4 cm (0.0 TS SDS). NAH correlated (r = 0.67) with (ranked) HT at GH start (+), 1 year responsiveness to GH (+), MPH (+), age at puberty onset (+), age at GH start (-), and dose (+). The same factors explained (R = 0.90) the total HT gain. However, HT at GH start correlated negatively. Karyotype had no influence on outcome. Evidently, height at GH start (the taller, the better), age at GH start (the younger, the better), the responsiveness to GH (the higher, the better) and age at puberty (the later, the better) determine NAH.
|
|
| 3. |
- Darendeliler, F., et al.
(författare)
-
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
-
Ingår i: Horm Res. ; 63:1, s. 40-7
-
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.
|
|
| 4. |
- Ranke, M. B., et al.
(författare)
-
Age at Growth Hormone Therapy Start and First-Year Responsiveness to Growth Hormone Are Major Determinants of Height Outcome in Idiopathic Short Stature
- 2007
-
Ingår i: Horm Res. - : S. Karger AG. - 0301-0163. ; 68:2, s. 53-62
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To develop methods to identify factors associated with a favorable outcome in GH-treated children with idiopathic short stature (ISS). Methods: From 4,685 children listed as having ISS within KIGS (Pfizer International Growth Database), we studied (a) the prediction model group (n = 657) to develop the first-year prediction model, and (b) the near adult height group (NAH; n = 256) which received GH for >4 years to develop descriptive models for adult height and overall height gain. Results: NAH group at GH start: age was 10.0 years, height -2.5 SD score (SDS), weight -2.3 SDS, height minus mid-parental height (MPH) -1.5 SDS; GH dose 0.19 mg/kg/week. Height gain was 1.1 SDS at a median age of 17.2 years. Growth response correlated positively with GH dose and weight at the start of GH treatment, and negatively with age and height SDS minus MPH SDS. The model explains 39% (error SD 1.2 cm) of the variability. Adult height correlated (R(2) = 0.64) positively with height at GH start, MPH and the first-year responsiveness to GH, and negatively with age. Conclusions: Prepubertal children with ISS who show an appropriate first-year response to GH are likely to benefit from long-term treatment, even on low GH dosages. Copyright (c) 2007 S. Karger AG, Basel.
|
|
| 5. |
- Ranke, M. B., et al.
(författare)
-
Increased response, but lower responsiveness, to growth hormone (GH) in very young children (aged 0-3 years) with idiopathic GH Deficiency: analysis of data from KIGS
- 2005
-
Ingår i: J Clin Endocrinol Metab. ; 90:4, s. 1966-71
-
Tidskriftsartikel (refereegranskat)abstract
- In children, GH secretion and sensitivity to GH are influenced by developmental changes. It is not clear whether the response to GH in very young children with GH deficiency (GHD) is the same as that in older, prepubertal children. A cohort of 265 children (180 males and 85 females) with idiopathic GHD from KIGS (Pfizer International Growth Database), with treatment started at less than 3 yr of age (mean age, 1.9 yr; group I) was compared with a cohort of 509 children (331 males and 178 females; group II) with treatment started at 7-8 yr of age (mean age, 7.5 yr). The following differences (P < 0.01) were found (given in mean values) between groups I and II at the start of GH treatment: 9% vs. 5% breech delivery, 38% vs. 14% multiple pituitary hormone deficiency, 4.2 vs. 5.9 ng/ml maximum GH in response to tests, -0.1 vs. -0.8 midparental height (MPH) sd score (SDS), -3.1 vs. -2.5 height SDS, 0.83 vs. 0.66 IU/kg.wk GH dose. After the first year of GH, the results were: 13.3 vs. 8.6 cm/yr height velocity, and 1.7 vs. 0.6 maximum change in height SDS. Using the previously developed growth prediction models for prepubertal children with idiopathic GHD more than 2 yr of age, our analysis revealed differences in the indexes of responsiveness in prediction models (Studentized residuals SDS, 0.7 vs.-0.3) and strikingly higher responsiveness to treatment among the young cohort, but with large scatter. Thus, new prediction models of height velocity (centimeters per year) were derived by means of multiple regression analysis for the young cohort, either involving (model A) or excluding (model B) the GH peak in tests. Model A explained 54% of the total variability with an error sd of 2.1 cm. Height velocity correlated with (parameters in order of importance) age (-), maximum GH (-), GH dose (+), weight SDS (+), height SDS minus MPH SDS (-), and birth weight SDS (+). Model B explained 45% of the total variability with an error sd of 2.3 cm. Height velocity correlated with (parameters in order of importance) age (-), GH dose (+), birth weight SDS (+), height SDS minus MPH SDS (-), and weight SDS (+). The predictors were qualitatively the same as those in the total prepubertal model involving all children more than 2 yr of age, but their quantitative impact in terms of partial contribution and the order of their importance were different for the young cohort. In particular, the partial contribution of the GH dose was higher, suggesting a greater gain in height per GH dose unit in the very young than in the older children. However, the rank order of the GH dose in the new models was lower, which suggests a slightly low sensitivity to GH in toddlers after the phase of severe GH insensitivity during early infancy. The early detection and GH treatment of congenital GHD is advantageous as a cost-effective strategy for achieving greater improvement of absolute height and growth velocity.
|
|
| 6. |
- Ranke, M. B., et al.
(författare)
-
Insulin-like growth factors as diagnostic tools in growth hormone deficiency during childhood and adolescence: the KIGS experience
- 2004
-
Ingår i: Horm Res. ; 62 Suppl 1, s. 17-25
-
Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) deficiency in children covers a spectrum of disorders involving an impairment in GH secretion and a clinical syndrome characterized by permanent stunting of growth. Ascertaining impairments in GH secretion directly is complex, especially if GH deficiency (GHD) is isolated and not caused by congenital or acquired pituitary defects or genetic abnormalities. It has been established that the concentrations of GH-dependent peptides, such as insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3), are low in patients with GHD. Their levels are, however, also influenced by a multitude of factors, such as age, gender, height, liver function, nutritional status and other hormones. In addition, the type of complex formed, e.g. either binary or ternary, may influence the measurements of IGFs and their binding proteins. Therefore, levels of IGF-I and IGFBP-3 are generally lower in short children compared with age-matched norms. The reported diagnostic value of sub-normal basal levels of IGF-I and IGFBP-3 is, in terms of sensitivity and specificity, approximately 70%. Thus, definite proof of GHD can only be achieved by means of GH measurements. As the diagnosis of GHD is somewhat unlikely if IGF testing shows normal values, it is clearly advantageous to schedule these tests as part of the initial diagnostic work-up in short children, as their implementation is not only practical but also inexpensive. The Pfizer International Growth Database (KIGS) analysis of IGF-I (n = 2,750) and IGFBP-3 (n = 1,300) levels in children with idiopathic GHD shows that these two parameters are now firmly embedded in diagnostic strategies around the world.
|
|
| 7. |
|
|
| 8. |
- Reiter, E. O., et al.
(författare)
-
Effect of Growth Hormone (GH) Treatment on the Final Height of 1258 Patients with Idiopathic GH Deficiency: Analysis of a Large International Database
- 2006
-
Ingår i: The Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:6
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Treatment with growth hormone (GH) has been used to correct the growth deficit in children with GH deficiency (GHD). Although successful in increasing height velocity, such treatment often falls short of helping patients achieve full genetic height potential. Objective: This study set out to analyze near final height data from a cohort of GH-treated children with idiopathic GHD. Design, Setting, and Participants: Of 1258 evaluable patients in the Pfizer International Growth Database (KIGS) with GHD, 980 were of Caucasian origin and 278 of Japanese origin; 747 had isolated GHD (IGHD), while 511 had multiple pituitary hormone deficiencies (MPHD). Main Outcome Measures: Near final height, relation to midparental height, and factors predictive of growth outcomes. Results: Median height SD scores (SDS) at start of treatment were -2.4 (IGHD) and -2.9 (MPHD) for Caucasian males and -2.6 (IGHD) and -3.4 (MPHD) for females, respectively; comparable starting heights were -2.9 (IGHD) and -3.6 (MPHD) for Japanese males and -3.3 (IGHD) and -4.0 (MPHD) for females, respectively. Corresponding near adult height SDS after GH treatment were -0.8 (IGHD) and -0.7 (MPHD) for Caucasian males and -1.0 (IGHD) and -1.1 (MPHD) for females, respectively; and -1.6 (IGHD) and -1.9 (MPHD) for Japanese males and -2.1 (IGHD) and -1.8 (MPHD) for females, respectively. Differences between near adult height and midparental height ranged between -0.6 and +0.2 SDS for the different groups, with the closest approximation to MPH occurring in Japanese males with MPHD. First-year increase in height SDS and prepubertal height gain were highly correlated with total height gain confirming importance of treatment before pubertal onset. Conclusions: It is possible to achieve final height within the midparental height range in patients with idiopathic GHD treated from an early age with GH, but absolute height outcomes remain in the lower part of the normal range. Patients with MPHD generally had a slightly better long term height outcome.
|
|
