| 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. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Growth hormone dose-dependent pubertal growth : a randomized trial in short children with low growth hormone secretion
- 2014
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 82:3, s. 158-170
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i. e. idiopathic isolated GH deficiency.Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height.Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS.Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.
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| 3. |
- Albin, Anna-Karin, et al.
(författare)
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Does growth hormone treatment influence pubertal development in short children?
- 2011
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 76:4, s. 262-72
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the influence of growth hormone (GH) treatment on the initiation and progression of puberty in short children. METHODS: This prospective, randomized, controlled study included 124 short children (33 girls) who received GH treatment (Genotropin(R); Pfizer Inc.) from a mean age of 11 years until near adult height [intent-to-treat (ITT) population]. Children were randomized into three groups: controls (n = 33), GH 33 mug/kg/day (n = 34) or GH 67 mug/kg/day (n = 57). Prepubertal children at study start constituted the per-protocol (PP) population (n = 101). Auxological measurements were made and puberty was staged every 3 months. Serum sex-steroid concentrations were assessed every 6 months. RESULTS: No significant differences were found between the groups, of both PP and ITT populations, in time elapsed from start of treatment until either onset of puberty, age at start of puberty or age at final pubertal maturation in either sex. In the ITT population, pubertal duration was significantly longer in GH-treated girls, and maximum mean testicular volume was significantly greater in GH-treated boys than controls, but there were no differences in testosterone levels between the groups. CONCLUSION: GH treatment did not influence age at onset of puberty and did not accelerate pubertal development. In boys, GH treatment appeared to increase testicular volume.
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| 4. |
- Benyi, E., et al.
(författare)
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Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence
- 2014
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 82:2, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. Methods: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. Results: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or nonmalignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-infinity) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. Conclusion: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort.
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| 5. |
- Chaplin, John, 1955, et al.
(författare)
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Growth Hormone Treatment Improves Cognitive Function in Short Children with Growth Hormone Deficiency
- 2015
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 83:6, s. 390-399
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: We investigated the association between cognition and growth hormone (GH) status and GH treatment in short prepubertal children with broadly ranging GH secretion. Methods: A total of 99 children (age 3-11 years), 41 with GH deficiency (GHD) and 58 with idiopathic short stature (ISS), were randomized to a fixed dose (43 mu g/kg/day) or a prediction model-guided individualized dose (17-100 mu g/kg/day) and followed up for 24 months. In a longitudinal and mixed within-and between-subjects study, we examined clinical effect size changes, measured by Cohen's d, in full-scale IQ (FSIQ) and secondary IQ indices. Results: Significant increases giving medium effect size in FSIQ (p = 0.001, Cohen's d = 0.63), performance IQ (p = 0.001, Cohen's d = 0.65) and processing speed (p = 0.005, Cohen's d = 0.71) were found in the GH-deficient group. In contrast, perceptual organization only increased in the ISS group (p = 0.001, Cohen's d = 0.53). Baseline IQ was normally distributed with small but significant differences between the groups: GH-deficient children had lower FSIQ (p = 0.042) and lower performance IQ (p = 0.021). Using multiple regression analysis, 40% of the variance in delta processing speed scores (0-24 months) was explained by GH(max) and IGF-I-SDS at baseline. Conclusion: IQ, specifically fluid intelligence, increased in the GH-deficient children. The pretreatment status of the GH/IGF-I axis was significantly predictive for these changes. (C) 2015 S. Karger AG, Basel
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| 6. |
- Chaplin, John, 1955, et al.
(författare)
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Improvements in Behaviour and Self-Esteem following Growth Hormone Treatment in Short Prepubertal Children
- 2011
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 75:4, s. 291-303
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: To evaluate effects of growth hormone (GH) treatment on behaviour and psychosocial characteristics in short-stature children. Methods: 99 referred prepubertal non-familiar short-stature children (32 GH deficiency; 67 idiopathic short stature) aged 3-11 years, randomized to fixed or individual GH doses and their parents completed questionnaires (Child Behaviour Checklist, Birleson Depression Self-Report Scale, Abbreviated Parent-Teacher Questionnaire, I Think I Am, Well-Being Visual-Analogue Scales for Short-Stature Children) at baseline (BL) and after 3, 12, and 24 months. Results: At BL, children showed higher levels of internalizing behaviour (p < 0.001), lower levels of externalizing behaviour (p < 0.006) and self-esteem (p < 0.001) compared to reference values. During GH treatment, behavioural measures (p < 0.001) and depression (p < 0.01) changed towards the mean of the population within the first 3 months and remained improved to 24 months. Self-esteem improved at all time points (p < 0.001), and in all subgroups, as did well-being dimensions stability and mood (p < 0.05). Multiple regression analysis showed that greater improvements were related to lower BL value, height gain, higher maximal GH value, being older, and being male. Conclusion: On GH treatment, prepubertal short children significantly improved on behavioural, depression, and psychosocial evaluations over a 2-year period of GH treatment. Most change occurred within the first 3 months, which highlights this short period as important not only for growth and metabolic changes but also for behaviour and psychosocial improvements following GH treatment.
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| 7. |
- Grönlund, Marita Andersson, 1959, et al.
(författare)
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Relationships between ophthalmological and neuropaediatric findings in children adopted from Eastern Europe.
- 2010
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Ingår i: Acta ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X .- 1395-3907 .- 1600-0420. ; 88:2, s. 227-34
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This study aimed to evaluate and relate visual function, ocular dimensions and neuropaediatric findings in adoptees from Eastern Europe. METHODS: We studied 72 of 99 children, born during 1990-95 and adopted from Eastern Europe to western Sweden during 1993-97. The children (mean age 7.5 years, range 4.8-10.5 years; 41 boys, 31 girls) were examined after a mean period of 5 years post-adoption by a multidisciplinary team. Correlations between ophthalmological findings and neuropaediatric data were analysed. RESULTS: Bivariate and regression analyses indicate a significant positive correlation between visual acuity (VA) and perceptual organization (p < 0.001), as well as between strabismus and verbal comprehension (p < 0.02). Fetal alcohol syndrome (FAS) was correlated with low VA (p < 0.02), subnormal stereovision (p < 0.009) and small optic discs (p < 0.02). Small head circumference was related to low VA (p < 0.015) and small optic discs (p < 0.03). Furthermore, small optic discs were related to low birthweight (p < 0.005) and preterm birth (p < 0.01). Large optic cups were correlated with poorer perceptual organization (p < 0.02). CONCLUSIONS: In this group of adoptees from Eastern Europe, ophthalmological findings were correlated to neuropaediatric findings, especially those arising from prenatal adverse events resulting in growth deficiency and central nervous system damage. Therefore, it is important and valuable with an ophthalmological examination in children adopted from Eastern Europe.
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| 8. |
- 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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| 9. |
- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 10. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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