| 1. |
- Ahlsson, Fredrik, et al.
(författare)
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Insulin Resistance, a Link between Maternal Overweight and Fetal Macrosomia in Nondiabetic Pregnancies
- 2010
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 74:4, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: During the last decades the number of large for gestational age infants delivered by nondiabetic mothers has increased. Our aim was to investigate to what extent fetal growth in nondiabetic pregnant women can be explained by rates of maternal energy substrate production and resting energy expenditure. Methods: Twenty nonsmoking pregnant women without impaired glucose tolerance and with a wide range of fetal weights (0.2-2.7 SDS) were investigated at 36 weeks of gestation. Maternal lipolysis, glucose production, resting energy expenditure, body composition and insulin resistance were assessed.Results: Median (range) glucose production rate was 805 (653-1,337) mumol/min and that of glycerol, reflecting lipolysis, was 214 (110-576) mumol/min. Multiple linear regression analysis showed that maternal fat mass explained 36% of the variation in insulin resistance, accounting for 62% of the variation in glucose production. Further, glucose production explained 31% of the variation in fetal weight. Resting energy expenditure explained 51% of the variation in estimated fetal weight. Conclusion: Fetal weight is dependent on maternal glucose production, which is in turn determined by the degree of insulin resistance, induced in part by the maternal fat mass. The variation in maternal resting energy expenditure is closely related to fetal weight.
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| 2. |
- Ahmed, SF, et al.
(författare)
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Promoting growth in chronic inflammatory disease: lessons from studies of the growth plate
- 2009
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Ingår i: Hormone research. - : S. Karger AG. - 1423-0046. ; 7272 Suppl 1, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Growth disorders are commonly observed in children with chronic inflammatory disease. It is likely that these disorders are mediated by a combination of factors, including the disease process and its treatment (with drugs such as glucocorticoids [GCs]). These factors affect the growth hormone-insulin-like growth factor I (IGF-I) axis, which is crucial for promoting linear growth at the level of the growth plate. Recent advances in our knowledge of the effects of GCs and proinflammatory cytokines on the growth plate have led to an improved understanding of the biological rationale for the use of growth-promoting therapy in children with chronic inflammatory disease and concurrent growth retardation. <i>Conclusions:</i> Both GCs and proinflammatory cytokines can adversely affect a number of components of growth plate chondrogenesis, and these effects can be ameliorated by raising local IGF-I exposure. However, this intervention does not lead to complete normalization of the growth plate. In children with chronic inflammation, the cornerstone of improving growth remains the judicious use of GCs while ensuring effective control of the disease process.
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| 3. |
- Akram, SK, et al.
(författare)
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Placental IGF-I, estrogen receptor, and progesterone receptor expression, and maternal anthropometry in growth-restricted pregnancies in the Swedish population
- 2011
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 75:2, s. 131-137
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Fetal growth restriction is a complex problem of pregnancy arising from multiple etiologies. Key regulatory elements of growth are the insulin-like growth factor (IGF) axis, and estrogen and progesterone receptors. The aims were to determine the relations of expression of IGF-I, estrogen receptors α and β (ERα and ERβ, respectively), and progesterone receptor (PR), with maternal anthropometry, focusing on birth weight outcomes. <i>Methods:</i> Placental samples were obtained from 33 patients following delivery. mRNA expression was determined by a solution hybridization technique. Samples were divided into normal control (NC) and growth-restricted (GR) groups. <i>Results:</i> IGF-I expression was lower in the GR as compared to the NC group. PR levels correlated positively with IGF-I expression, infant anthropometry, and gestational age (GR). ERα correlated positively with PR expression (NC), and maternal BMI at delivery (GR). ERβ correlated positively with maternal delivery weight and gestational age (NC). <i>Conclusion:</i> The differences in placental expression of IGF-I emphasize its key role in birth weight outcomes. We further suggest the importance of PR expression in the pathogenesis of intrauterine growth restriction, as there were direct correlations of PR expression with both IGF-I expression and infant anthropometric parameters, as well as gestational age.
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| 4. |
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| 5. |
- 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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| 6. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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New Reference for Height in Swedish Boys and Girls
- 2014
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Ingår i: Hormone Research in Paediatrics. 82 (suppl 1), s. 256. 53rd Annual Meeting of the European Society for Paediatric Endocrinology (ESPE). Dublin, Ireland, September 18-20, 2014. Hormone Research in Paediatrics.. - : S. Karger AG. - 1663-2818 .- 1663-2826.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The actual Swedish growth references are based on a cohort born 1974. Objective and hypotheses: Due to secular changes there is need for new height references. Method: Material: Height measurements from birth to adult height (AH) in a cohort of healthy, Nordic and born full term 1990, 20.796 from 1647 boys, 19.202 from 1501 girls were used (ALL) and compared to both a subgroup with puberty close to mean (PHV G0.25 years) of 3.726 heights from 259 boys; 3.759 from 271 girls, and a subgroup (AM) with O10 height measurements evenly distributed (15.324 in 989 boys; 14.381 in 919 girls), and of high data quality. The 1974 cohort, with similar subgrouping, were used for comparison. Methods: For construction of height curves the LMS method was applied with LMS parameters based directly on the data: the power in the Box-Cox transformation (L), the median (M), and the generalized coefficient of variation (S). The GAMLSS R-package with a special LMS program was used, giving L, M, S and optional kurtosis as functions of age. Results: Height reference curves, with mean, G1, G2 SDS were obtained for 1990 of the ALL vs the AM material with similar results whereas the close puberty material showed the same mean but more narrow G1, G2 SDS during adolescence. When the different 1990 references were compared to 1974 references, the corresponding 1974 differences were found. The new references takes into account that the 1990 cohort had a more rapid infancy growth, increased prepubertal growth, especially in boys, increased pubertal gain, only in girls, and increased AH in both genders.
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| 7. |
- 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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| 8. |
- Albin, Anna-Karin, et al.
(författare)
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Estradiol and Pubertal Growth in Girls.
- 2012
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 78:4
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The objective of this study was to determine estradiol levels and assess their relationship to pubertal growth in girls. Methods: Thirty-seven 24-hour profiles of serum 17β-estradiol were retrospectively analyzed in relation to growth in 27 healthy girls admitted for short/tall stature (n = 20) or recruited as healthy volunteers at Göteborg Pediatric Growth Research Center (GP-GRC). Inclusion Criteria: Birth weight and length above -2 SDS, gestational age 37-42 weeks, prepubertal height and weight within ±3 SDS and normal growth hormone secretion. Serum estradiol was determined by a validated ultrasensitive extraction radioimmunoassay (detection limit 4 pmol/l). A sixth-grade polynomial was fitted to each girl's growth data. Growth velocity and age at peak height velocity (PHV) was calculated. Results: A dose-response model was used to find the morning 17β-estradiol level at which half of the maximal pubertal growth up to PHV had occurred, EC(50), which was 20 pmol/l with a 95% confidence interval of 13-31. When 17β-estradiol exceeds early pubertal levels (Tanner breast stage 2, 10-51 pmol/l), less than 25% of the potential pubertal growth velocity up to PHV remains. Conclusions: Morning 17β-estradiol in the low early pubertal range (13-31 pmol/l) is associated with increasing growth velocity.
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| 9. |
- Albin, Anna-Karin, et al.
(författare)
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Pubertal growth and serum testosterone and estradiol levels in boys.
- 2013
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Ingår i: Hormone research in pædiatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 80:2, s. 100-10
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: To study serum testosterone and estradiol in healthy boys in relation to growth during puberty up to peak height velocity (PHV). Methods: Growth velocity was analyzed through testosterone (n = 41) and 17β-estradiol (n = 37) 24-hour profiles in a dose-response model. Participants were 26 healthy boys admitted for short or tall stature or participating as healthy volunteers at the Queen Silvia Children's Hospital. Other inclusion criteria included the following: gestational age 37-42 weeks, birth weight and length >-2 standard deviation score (SDS) and prepubertal height and weight within ±3 SDS. Testosterone was measured using a modified radioimmunoassay (RIA) with a detection limit of 0.03 nmol/l. Estradiol was determined using an ultrasensitive extraction RIA with a detection limit 4 pmol/l. A sixth-grade polynomial was fitted to each child's growth data, giving growth velocity and age at PHV. Results: Growth velocity increased by 50% from prepubertal growth to PHV at a morning testosterone level of 3.1 nmol/l (95% confidence interval 2.4-4.2), EC50. The corresponding EC50 of 17β-estradiol was 6.5 pmol/l (3.2-13). Boys approaching PHV (<4% remaining) had morning testosterone levels >10 nmol/l and 17β-estradiol >9 pmol/l. Conclusion: Observed early puberty/initial mid puberty morning testosterone levels of 2.4-4.2 nmol/l are associated with a 50% increase in growth velocity from prepubertal growth to PHV in healthy boys.
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| 10. |
- Allbrand, Marianne, 1958-, et al.
(författare)
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Adipocytokines in placenta and cord blood in relation to maternal obesity, and foetal and postnatal growth of the child
- 2015
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Ingår i: Hormone Research in Paediatrics. - Basel, Switzerland : S. Karger. - 1663-2818 .- 1663-2826. ; 82:Suppl. 1, s. 47-48
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The nutritional and hormonal state in utero may be a link between maternal obesity and obesity in the offspring. The gene expression in placentae in pregnancies complicated by diabetes is reduced for leptin, but increased for ghrelin. It is not known whether these genes’ expressions in placentae are altered in maternal obesity.Objectives and hypotheses: To compare obese and normal-weight women and their children concerning gene expressions of leptin and ghrelin in placentae; leptin, ghrelin, adiponectin, and C-peptide levels in cord blood, birth size and postnatal growth. Changes in the expression of these adipocytokines may lead to an altered hypothalamic sensitivity to leptin and ghrelin resulting in an increased risk of obesity in the offspring.Method: 32 women with pre-pregnancy obesity, but otherwise healthy, were compared to 32 matched, normal-weight controls. Full-term placenta biopsies were analysed with qPCR for leptin mRNA and ghrelin mRNA. Cord blood samples were examined with ELISA for leptin, ghrelin, adiponectin, and C-peptide concentrations. Birth size and postnatal growth of the children were collected from clinical registers at the Child Health Care Units.Results: The leptin and ghrelin gene expressions in placentae did not differ between obese and normal-weight women. The leptin concentration in cord blood was higher in children of obese mothers (P=0.021). It correlated with birth weight Z-score (r=0.467, P<0.001) and C-peptide level in cord blood (r=0.446, P<0.001). Children of obese women were slightly heavier at birth, but postnatal growth did not differ between groups. Children with birth weight ≤−0.67 Z-score had higher ghrelin levels in cord blood than heavier children (P=0.042). The leptin level in cord blood correlated negatively with weight gain at 6 months (r=−0.332, P=0.009). The ghrelin level in cord blood correlated with weight gain at 3 months in girls (r=0.611, P=0.001), but not in boys. The adiponectin level in cord blood correlated negatively with length gain at 3 years in the obese group (r=−0.571, P=0.033), but not in the normal-weight group.Conclusion: Leptin and ghrelin placental gene expressions are not altered in obese women, but foetal adipocytokine production may influence early postnatal growth, possibly by influencing hunger signalling or insulin levels
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| 11. |
- 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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| 12. |
- Andrade, Anenisia C., et al.
(författare)
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New Genetic Diagnoses of Short Stature Provide Insights into Local Regulation of Childhood Growth
- 2017
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 88:1, s. 22-37
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Forskningsöversikt (refereegranskat)abstract
- Idiopathic short stature is a common condition with a heterogeneous etiology. Advances in genetic methods, including genome sequencing techniques and bioinformatics approaches, have emerged as important tools to identify the genetic defects in families with monogenic short stature. These findings have contributed to the understanding of growth regulation and indicate that growth plate chondrogenesis, and therefore linear growth, is governed by a large number of genes important for different signaling pathways and cellular functions, including genetic defects in hormonal regulation, paracrine signaling, cartilage matrix, and fundamental cellular processes. In addition, mutations in the same gene can cause a wide phenotypic spectrum depending on the severity and mode of inheritance of the mutation.
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| 13. |
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| 14. |
- Andrade, AC, et al.
(författare)
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Hormones and genes of importance in bone physiology and their influence on bone mineralization and growth in Turner syndrome
- 2010
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 73:3, s. 161-165
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Tidskriftsartikel (refereegranskat)abstract
- This mini review summarizes papers presented in a Joint Symposium between the Bone, Growth Plate and Turner Syndrome Working Groups of the European Society for Paediatric Endocrinology (ESPE) that was held on September 9, 2009, in New York.The program had been composed to give an update on hormones and genes of importance in bone physiology and their influence on bone mineralization and growth in Turner syndrome. This paper summarizes the data and highlights the main topics and discussions related to each presentation.
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| 15. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Physiological Estrogen Replacement Therapy for Puberty Induction in Girls : A Clinical Observational Study
- 2014
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 81:4, s. 239-244
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: The goal of estrogen replacement therapy (ERT) in girls with hypogonadism is to achieve the endocrine milieu similar to natural puberty, where transdermal administration is the most physiological route. The aim of the study was to evaluate guidelines for the induction of puberty with transdermal estradiol (E-2) patches in a large outpatient setting. Methods: In a retrospective study, serum E-2 levels from 18 clinics were analyzed at the Goteborg Pediatric Growth Research Center laboratory, as part of the initiation of ERT in girls with hypogonadism. Exclusion criteria were pubertas tarda and pubertal arrest. Eighty-eight observations (50 with Turner syndrome, TS) were included. Serum E-2 levels were determined by extraction + radioimmunoassay (detection limit 4 pmol/l) and analyzed in relation to the dose of Evorel (R) (25 mu g/24 h, containing 1.60 mg estradiol hemihydrate; Janssen-Cilag Pharmaceutica N.V., Beerse, Belgium). Results: There was a linear relationship between serum E-2 and the weight-based dose, with r = 0.56, p < 0.0001 for all observations and r = 0.59, p < 0.0001 for the TS study group. Linear regression analysis for doses of 0.05-0.07 mu g/kg resulted in serum levels of 17-23 pmol/l (TS 17-24 pmol/l) and doses of 0.08-0.12 mu g/kg in 26-39 pmol/l (TS 27-39 pmol/l). Conclusions: For the initiation of ERT with nocturnally administered E-2 patches, we recommend reduced starting doses of 0.05-0.07 mu g/kg, with the goal of mimicking E-2 levels during gonadarche. In older girls, when breast development is of high priority, the starting dose can still be 0.08-0.12 mu g/kg. (C) 2014 S. Karger AG, Basel
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| 16. |
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| 17. |
- Backeljauw, Philippe, et al.
(författare)
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Safety and Effectiveness of Recombinant Human Growth Hormone in Children with Turner Syndrome : Data from the PATRO Children Study
- 2021
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 94:3-4, s. 133-143
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: PATRO Children is an international, observational, postmarketing surveillance study for a biosimilar recombinant human growth hormone (rhGH; somatropin, Omnitrope (R); Sandoz), approved by the European Medicines Agency in 2006. We report safety and effectiveness data for patients with Turner syndrome (TS).Methods: The study population included infants, children, and adolescents with TS who received Omnitrope (R) treatment according to standard clinical practice. Adverse events (AEs) were monitored for safety evaluation, and height velocity (HV), height standard deviation score (HSDS), and HVSDS were calculated to evaluate treatment effectiveness.Results: As of August 2019, 348 TS patients were enrolled from 130 centers. At baseline, 314 patients (90.2%) were prepubertal and 284 patients (81.6%) were rhGH treatment naive. The mean ( range) age at baseline was 9.0 (0.7-18.5) years, and mean (SD) treatment duration in the study was 38.5 (26.8) months. Overall, 170 patients (48.9%) reported AEs, which were considered treatment related in 25 patients (7.2%). One treatment-related serious AE was reported (intracranial hypertension). Mean.HSDS after 3 years of therapy was +1.17 in treatment-naive prepubertal patients and +0.1 in pretreated prepubertal patients. In total, 51 patients (31.1%) reached adult height (AH), 35 of whom were rhGH treatment naive; in these patients, mean (SD) HSDS was -2.97 (1.03) at the start of Omnitrope (R) treatment, and they achieved a mean (SD) AHSDS of -2.02 (0.9).Conclusion: These data suggest that biosimilar rhGH is well tolerated and effective in TS patients managed in reallife clinical practice. Optimization of rhGH dose may contribute to a higher AH. (C) 2021 S. Karger AG, Basel
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| 18. |
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| 19. |
- Bang, Peter, et al.
(författare)
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Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex (R) Growth Forum Database Experience
- 2015
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Ingår i: Hormone Research in Paediatrics. - : KARGER. - 1663-2818 .- 1663-2826. ; 83:5, s. 345-357
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: We report data from the EU Increlex (R) Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. Methods: Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. Results: Mean +/- SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 +/- 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naive to treatment, this was 7.3 +/- 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). Conclusion: Safety and effectiveness data on use of rhIGF-1 in a real-world setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia. (C) 2015 S. Karger AG, Basel
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| 20. |
- Bang, P, et al.
(författare)
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Free insulin-like growth factor I: are we hunting a ghost?
- 2001
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Ingår i: Hormone research. - : S. Karger AG. - 0301-0163. ; 5555 Suppl 2, s. 84-93
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Tidskriftsartikel (refereegranskat)abstract
- During the last decade, there has been an increasing number of publications reporting concentrations of free dissociable insulin-like growth factor I (IGF-I) in serum or plasma. The goal for attempting to measure free IGF-I in a serum sample in vitro has been to obtain information about the bioactivity of IGF-I in target tissues, and thus relate a measurable parameter to biological responses such as longitudinal growth or glucose disappearance rate. In this review, the serum free IGF-I approach is placed into a physiological perspective. In addition, methodological aspects are discussed and suggestions for the validation of free IGF-I assays are presented.
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| 21. |
- Bang, Peter, 1959-
(författare)
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Principles of Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children with Idiopathic Short Stature
- 2011
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Ingår i: HORMONE RESEARCH IN PAEDIATRICS. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 76:s3, s. 24-26
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Tidskriftsartikel (refereegranskat)abstract
- Until recently, growth hormone (GH) was the only treatment available to improve growth rate in short, prepubertal children. Insulinlike growth factor I (IGF-I) is now approved in the United States and the European Union for treatment of short stature in children with severe primary IGF-I deficiency, a condition characterized by unresponsiveness to GH in IGF-I-producing tissues. This has increased the focus on the growth response to GH therapy in short children treated according to current recommendations. In particular, children with idiopathic short stature (ISS) may have some degree of GH insensitivity that decreases their response to GH treatment. This minireview discusses data on the response to GH treatment in patients with ISS and recent studies on the use of IGF-I in subgroups of patients with ISS. The rationale for future combination treatment with GH plus IGF-I is also discussed.
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| 22. |
- Barbaro, M, et al.
(författare)
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Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1) locus enables explanation of phenotypic differences in patients with X-linked congenital adrenal hypoplasia
- 2012
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 77:2, s. 100-107
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aim:</i>X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It is caused by deletions or point mutations of the <i>NR0B1 </i>gene, on Xp21. AHC can be associated with glycerol kinase deficiency, Duchenne muscular dystrophy and mental retardation (MR), as part of a contiguous gene deletion syndrome. A synthetic probe set for multiplex ligation-dependent probe amplification analysis was developed to confirm and characterize <i>NR0B1</i> deletions in patients with AHC and to correlate their genotypes with their divergent phenotypes. <i>Results:</i>In 2 patients, isolated AHC was confirmed, while a patient at risk for metabolic crisis was revealed as the deletion extends to the <i>GK</i> gene. A deletion extending to <i>IL1RAPL1</i> was confirmed in both patients showing MR. Thus, a good genotype-phenotype correlation was confirmed. <i>Conclusions:</i>Multiplex ligation-dependent probe amplification analysis is a valuable tool to detect <i>NR0B1</i> and contiguous gene deletions in patients with AHC. It is especially helpful for <i>IL1RAPL1 </i>deletion detection as no clinical markers for MR are available. Furthermore, multiplex ligation-dependent probe amplification has the advantage to identify female carriers that, depending on the deletion extension, have a high risk of giving birth to children with MR, AHC, glycerol kinase deficiency and Duchenne muscular dystrophy.
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| 23. |
- Baroncelli, Marta, et al.
(författare)
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Bone, Growth Plate and Mineral Metabolism
- 2021
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 94:Suppl. 1, s. 22-22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The skeletal research field develops rapidly and has produced several exciting findings in the last year and includes advances in the treatment of rare skeletal disorders and an ever deeper under-standing into the fundamental molecular mechanisms that control skeletal development, metabolism, growth, and mineralization.The targeting of the C-type natriuretic peptide (CNP) pathway and options to directly antagonize the overactivity of the FGFR3 pathway in achondroplasia continues to be a subject of high inter-est and excitement and in the 2021 yearbook we highlight the dou-ble-blind, randomized placebo-controlled phase 3 study of a CNP analogue (vosoritide) in children with achondroplasia. We also highlight the identification of a novel gene for autosomal domi-nant hypophosphatemic rickets, publication of new growth charts for X-linked hypophosphatemia and two large well-designed pae-diatric vitamin D trials for the prevention of tuberculosis and asthma exacerbation, respectively.Translational highlights include review on the recent advances of mineral metabolism and biomineralization, in vivo data sug-gesting that modification of the synovial microenvironment may allow endogenous skeletal stem cells to form hyalin cartilage and thereby heal articular cartilage injuries, as well as a study using gene targeting in zebra fish to reveal the pathogenic mechanism by which mutations in CRTAP and P3H1 causes osteogenesis imper-fecta type VII and VIII, respectively.Advances in the understanding of skeletal biology a study by McDonald et al. that challenges the current dogma on the origin and fate of osteoclasts as they show evidence that multinucleated osteoclasts can fission into daughter cells, a.k.a. osteomorphs, that subsequently are recycled into bone resorbing osteoclasts via a RANKL-dependent process. Additional articles in this section directly and indirectly highlight the critical role of loading and mechanical stress on the growing skeleton. Several of these excit-ing findings will be highlighted in the presentation.
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| 24. |
- Bendre, Ameya, et al.
(författare)
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Growth failure in aggrecan haploinsufficiency is due to a decrease in growth plate matrix volume and hypertrophic cell size
- 2023
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 96:Suppl. 4, s. 40-41
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Heterozygous loss-of-function mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with advanced bone age, early-onset osteoarthritis and intervertebral disc disease (SSOAOD; OMIM#165800). ACAN mutations is a relatively common finding in idiopathic short stature (ISS) and has been reported to be the cause of growth failure in approximately 2% of children with ISS. However, the underlying cellular and molecular mechanisms by which ACAN mutations cause growth failure in SSOAOD have not been elucidated.Objective: To investigate the underlying cellular and molecular mechanisms of growth failure using a mouse model of SSOAOD.Methods: Cartilage matrix deficiency mouse (Acan cmd) has a naturally occurring 7 bp micro-deletion in aggrecan gene. Heterozygous Acancmd and wild-type (WT) male and female mice were assessed for skeletal and body growth at 1,3,6,12 and 24 weeks of age. Histomorphometric analysis was performed on Masson-Trichrome stained proximal tibial and distal femoral growth plates. Cell proliferation was assessed by EdU incorporation. Quantification of percentage matrix area was performed using Image J. Single-cell RNA sequencing was carried out on chondro-cytes isolated from 18 day old WT and Acan cmd female mice according to 3’ gene expression protocol (10X Genomics).Results: Heterozygous Acancmd mice were born at a normal size and similar to humans with SSOAOD but showed decreased postnatal growth resulting in a gradually worsening dwarfism with reduced total body length and tibial and femoral lengths (p<0.0001). In the growth plates, chondrocytes were found to be more tightly packed with reduced matrix area (p<0.0001) and increased column density in Acan cmd mice compared to WT mice. Growth plate height (p<0.0001), heights of the individual zones (p<0.001), the number of resting zone chondrocytes (p<0.01), proliferative cells per column (p<0.0001), and the size of terminal hypertrophic chondrocytes (p<0.001) were slightly reduced in both male and female Acan cmd mice, especially at 1 week of age. Interestingly, chondrocyte proliferation was similar in Acan cmd and WT mice at all time-points assessed (p=0.90). Female Acan cmd mice exhibited a more pronounced phenotype than male mice.Conclusions: Similar to children with heterozygous ACAN mutations, heterozygous Acancmd mice exhibit a growth pattern with postnatal growth failure resulting in adult short stature. The growth failure is primarily caused by decreased matrix production and hypertrophic cell size, whereas chondrocyte proliferation is normal. Single-cell RNA sequencing of growth plate chondrocytes is ongoing and will identify the underlying pathogenic mechanisms and might also identify compensatory mechanisms limiting the effects of aggrecan haploinsufficiency.
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| 25. |
- Bendre, Ameya, et al.
(författare)
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Postnatal growth failure of aggrecan deficient mice is due to impaired growth plate chondrogenesis
- 2022
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 95:Suppl. 2, s. 294-294
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Heterozygous Aggrecan (Acan) mutations cause autosomal short stature (ISS) with advanced bone age, early-onset osteoarthritis and intervertebral disc disease (OMIM#165800) in humans. Cartilage matrix deficiency mouse (Acancmd) has a naturally occurring 7 bp micro-deletion in aggrecan gene. Heterozygous Acancmd mice develop postnatal dwarfism with progressing age. However, the underlying cellular and molecular mechanisms causing the growth failure have not been characterized in detail.Objective: To investigate the molecular mechanism of proportionate dwarfism in heterozygous Acan cmd mouse.Methods: Heterozygous Acancmd and wild-type (WT) male and female mice were assessed for skeletal and body growth, at 1, 3, 6, 12 and 24 weeks of age. Histomorphometric analysis was performed on Masson-Trichrome stained proximal tibial and femoral growth plates. Cell proliferation was assessed by EdU incorpora-tion and assessed by confocal microscopy. Quantification of percentage matrix area was performed using Image J image analysis software.Results: Heterozygous Acancmd mice were born with a normal body size. However, postnatal growth was reduced resulting in a gradually worsening dwarfism with reduced total body length (p <0.0001) as well as shorter tibial length (p<0.0001) and femoral length (p<0.0001) than their wild-type littermates. Histomorphometric analyses revealed that growth plate chondrocytes were more tightly packed with reduced matrix area (p<0.001) and increased proliferative column density in Acancmd mice compared to wild-type mice. Interestingly, the number of resting zone chondrocytes, proliferative cells per column and hypertropic cells per column were reduced at 1 week of age. In contrast, the size of terminal hypertrophic chondrocytes were normal during early postnatal growth, but reduced at 12 and 24 weeks of age. Despite the differences in growth plate morphology, chondrocyte proliferation was similar in Acan cmd and WT mice. Interestingly, female mice exhibited a more pronounced growth phenotype than the males.Conclusions: Heterozygous Acan cmd mice have a growth disorder that is similar to that in children with heterozygous ACAN mutations in terms of progression with age as well as in magnitude (10-15% smaller). Histomorphometric analyses suggest that the growth failure of aggrecan deficient mice is due to a combination of reduced matrix production and decreased size of the terminal hypertrophic chondrocytes. Further studies will elucidate the pathogenic mechanisms as well as the effect of estrogen on growth in aggrecan haploinsufficiency.
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| 26. |
- 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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| 27. |
- Benyi, E, et al.
(författare)
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The Physiology of Childhood Growth: Hormonal Regulation
- 2017
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 88:1, s. 6-14
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Tidskriftsartikel (refereegranskat)abstract
- The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.
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| 28. |
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| 29. |
- Berg, U, et al.
(författare)
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Exercise and circulating insulin-like growth factor I
- 2004
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Ingår i: Hormone research. - : S. Karger AG. - 0301-0163. ; 6262 Suppl 1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Determinations of serum concentrations of total insulin-like growth factor I (tIGF-I) are important in the diagnosis, monitoring of treatment and safety evaluation of patients with growth disorders and/or metabolic disease. It is well established that tIGF-I status varies over time. Changes in tIGF-I levels in relation to an acute bout of exercise or repeated bouts, known as training, are likely to contribute to this variation. Serum tIGF-I has also been found to be of predictive value in growth prediction models employed before the start of growth hormone (GH) treatment. Furthermore, IGF-I generation tests have been suggested to be of value in the assessment of the growth response to GH administration in patients suspected of GH deficiency with or without some degree of GH insensitivity. This is discussed elsewhere in this issue. Recent progress in our understanding of growth hormone-dependent and -independent expression of the <i>IGF1</i> gene in skeletal muscle and the role of sufficient energy intake during training for muscle and liver generation of IGF-I raises important questions regarding their relative contribution to the circulating pool of IGF-I. The present review is focused on circulating levels of tIGF-I in relation to a single bout of exercise or to a period of training. In addition, the expression of IGF-I locally in muscle in response to these stimuli will be discussed.
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| 30. |
- Bergstrom, I, et al.
(författare)
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Vitamin D levels in children born to vitamin D-deficient mothers
- 2013
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 80:1, s. 6-10
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Aim:</i></b> To determine whether a standard daily dose of 400 IU vitamin D is sufficient to normalize vitamin D levels in infants born to vitamin D-deficient mothers. <b><i>Methods:</i></b> The children were recruited from a study cohort of 68 immigrant and 51 non-immigrant pregnant women living in Stockholm. The women were monitored at 12 weeks of pregnancy, at delivery and together with their children, 6-18 months after birth. During pregnancy, most immigrant women (78%) had 25(OH)D<sub>3</sub> levels <25 nmol/l. We here report the outcome of 25 infants born to these mothers. All infants received a daily supplementation dose of 400 IU vitamin D from 2 weeks of age. <b><i>Results:</i></b> At birth, most children in the immigrant group were vitamin D-deficient (23.3 nmol/l (12-54); mean and range) while at 6-18 months of age vitamin D levels were essentially normalized (82.8 nmol/l (38-142)) although 4 children still had subnormal levels consistent with vitamin D insufficiency. <b><i>Conclusion:</i></b> A daily recommended supplementation dose of 400 IU vitamin D is sufficient in most children of vitamin D-deficient immigrant women living in Sweden.
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| 31. |
- Binder, G, et al.
(författare)
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GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice
- 2020
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 92:3, s. 150-156
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. <b><i>Methods:</i></b> A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. <b><i>Results:</i></b> National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. <b><i>Conclusions:</i></b> GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence.
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| 32. |
- Bizzarri, C, et al.
(författare)
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Growth Trajectory in Children with Type 1 Diabetes Mellitus: The Impact of Insulin Treatment and Metabolic Control
- 2018
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 89:3, s. 172-177
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Linear growth was reported to be negatively affected by type 1 diabetes mellitus (T1DM), in relation to disease duration and poor metabolic control. It is unclear whether a subtle growth failure still persists despite the optimization of therapy. Our aim was to analyse pubertal growth, adult height, and metabolic profile in a cohort of children with T1DM undergoing intensive insulin treatment by multiple daily injections or continuous subcutaneous insulin infusion (CSII). <b><i>Methods:</i></b> One-hundred and four children (51 males) with prepubertal onset of T1DM were prospectively followed up to final height attainment. <b><i>Results:</i></b> Age at puberty onset was 11.7 ± 1.1 years in males and 10.9 ± 1.3 in females. Age at adult height attainment was 16.4 ± 1.6 years in males and 14.1 ± 1.8 years in females. Pubertal height gain was 24.4 ± 4.9 cm in males and 19.0 ± 3.8 cm in females. HbA<sub>1c</sub>, HDL cholesterol, and triglyceride levels increased during puberty. HDL cholesterol levels were higher in patients treated with CSII. Height standard deviation score (SDS) at diagnosis (0.52 ± 1.04) was higher than target height SDS (0.01 ± 1.07), but declined afterwards, and both height SDS at puberty onset (0.22 ± 1.1) and adult height SDS (–0.1 ± 1.02) were not significantly different from target height SDS. BMI SDS showed a positive trend from diagnosis to puberty onset and stabilized later (–0.04 ± 1.4 at T1DM onset, 0.55 ± 2.1 at puberty onset, and 0.53 ± 2.1 at adult height attainment). <b><i>Conclusions:</i></b> Although subtle abnormalities of growth still persist, the modern advancements of insulin therapy are able to normalize puberty and final height of children with T1DM.
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| 33. |
- Bizzarri, C, et al.
(författare)
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Residual β-cell mass influences growth of prepubertal children with type 1 diabetes
- 2013
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 80:4, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> The growth deceleration observed in children with type 1 diabetes (T1D) has been related to poor glycemic control. It is unclear whether growth impairment persists despite the optimization of therapy. We analyzed the effects of intensive insulin treatment on prepubertal growth. <b><i>Methods:</i></b> One hundred and four T1D children were evaluated from T1D diagnosis up to puberty onset. Height, weight, insulin requirement and glycated hemoglobin (HbA1c) were recorded at 3- to 6-month intervals. Residual β-cell mass was estimated by fasting C-peptide at T1D onset. <b><i>Results:</i></b> Age at T1D onset was 5.91 ± 1.9 years. Follow-up duration was 4.84 ± 1.58 years. Height velocity standard deviation score (SDS) was -0.14 ± 1.84. Height SDS changed from 0.52 ± 1.04 at T1D onset, to 0.36 ± 1.10 at the end of follow-up (p = 0.04). BMI SDS increased from -0.04 ± 1.48 to 0.32 ± 1.03 (p = 0.01). Multivariate analysis showed that height velocity was directly affected by C-peptide (p = 0.03) and insulin requirement (p = 0.004) and inversely related to HbA1c (p = 0.006). BMI gain was negatively influenced by HbA1c (p = 0.01) and positively related to T1D duration (p = 0.01). <b><i>Conclusion:</i></b> Despite insulin intensive therapy, T1D still negatively affects growth. Residual β-cell mass has a direct positive impact on growth, independently from the quality of glycemic control.
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| 34. |
- Bizzarri, C, et al.
(författare)
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Water Balance and 'Salt Wasting' in the First Year of Life: The Role of Aldosterone-Signaling Defects
- 2016
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 86:3, s. 143-153
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Tidskriftsartikel (refereegranskat)abstract
- In newborns and infants, dehydration and salt wasting represent a relatively common cause of admission to hospital and may result in life-threatening complications. Kidneys are responsible for electrolyte homoeostasis, but neonatal kidneys show low glomerular filtration rate and immaturity of the distal nephron, leading to reduced ability to concentrate urine. High extrarenal fluid losses often contribute to the increased occurrence of electrolyte disorders. Aldosterone is essential for sodium retention in the kidney, salivary glands, sweat glands and colon. A partial and transient aldosterone resistance is present in newborns and infants, thus reducing the capability of maintaining sodium balance in specific pathological conditions. The present review examines the mechanisms making infants more susceptible to salt wasting. Peculiar aspects of renal physiology in the first year of life and management of electrolyte disorders (i.e. sodium and potassium) are considered. Finally, inherited disorders associated with neonatal salt wasting are examined in detail.
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| 35. |
- 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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| 36. |
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| 37. |
- Bruett, Anna Levke, et al.
(författare)
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Assessment of Health-Related Quality of Life and Patient Satisfaction in Children and Adolescents with Growth Hormone Deficiency or Idiopathic Short Stature - Part 1 : A Critical Evaluation of Available Tools
- 2009
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Ingår i: Hormone Research. - : S. Karger AG. - 0301-0163 .- 1423-0046. ; 72:2, s. 65-73
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Forskningsöversikt (refereegranskat)abstract
- The concept of health-related quality of life (HrQoL) reflects the subjective perception of health and includes aspects of well-being and functioning in physical, emotional, mental and social life domains. Nowadays, HrQoL has become a relevant treatment outcome from epidemiological and clinical perspectives and is also broadly employed in health economic analyses. To assess HrQoL generic as well as condition-specific instruments are used. The former are applicable to a wide range of health conditions and aim at measuring HrQoL across different conditions. The latter focus on capturing the impact of a specific disease. Although HrQoL research in adults is now well-advanced, there are still open questions regarding how to assess HrQoL in pediatric conditions, such as short stature. Eight generic (one chronic-generic) and seven condition-specific (one treatment-specific) instruments used in HrQoL research in short stature of youth are described. Additionally, this mini review identifies a need for further research and indicates potential directions.
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| 38. |
- Bullinger, M., et al.
(författare)
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Cross-Cultural Equivalence of the Patient- and Parent-Reported Quality of Life in Short Stature Youth (QoLISSY) Questionnaire
- 2014
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 82:1, s. 18-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Testing cross-cultural equivalence of patient-reported outcomes requires sufficiently large samples per country, which is difficult to achieve in rare endocrine paediatric conditions. We describe a novel approach to cross-cultural testing of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire in five countries by sequentially taking one country out (TOCO) from the total sample and iteratively comparing the resulting psychometric performance. METHODS: Development of the QoLISSY proceeded from focus group discussions through pilot testing to field testing in 268 short-statured patients and their parents. To explore cross-cultural equivalence, the iterative TOCO technique was used to examine and compare the validity, reliability, and convergence of patient and parent responses on QoLISSY in the field test dataset, and to predict QoLISSY scores from clinical, socio-demographic and psychosocial variables. RESULTS: Validity and reliability indicators were satisfactory for each sample after iteratively omitting one country. Comparisons with the total sample revealed cross-cultural equivalence in internal consistency and construct validity for patients and parents, high inter-rater agreement and a substantial proportion of QoLISSY variance explained by predictors. CONCLUSION: The TOCO technique is a powerful method to overcome problems of country-specific testing of patient-reported outcome instruments. It provides an empirical support to QoLISSY's cross-cultural equivalence and is recommended for future research. (c) 2014 S. Karger AG, Basel.
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| 39. |
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| 40. |
- Butler, Eadaoin M., et al.
(författare)
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Prediction Models for Early Childhood Obesity : Applicability and Existing Issues
- 2018
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Ingår i: Hormone Research in Paediatrics. - : KARGER. - 1663-2818 .- 1663-2826. ; 90:6, s. 358-367
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Forskningsöversikt (refereegranskat)abstract
- Statistical models have been developed for the prediction or diagnosis of a wide range of outcomes. However, to our knowledge, only 7 published studies have reported models to specifically predict overweight and/or obesity in early childhood. These models were developed using known risk factors and vary greatly in terms of their discrimination and predictive capacities. There are currently no established guidelines on what constitutes an acceptable level of risk (i.e., risk threshold) for childhood obesity prediction models, but these should be set following consideration of the consequences of false-positive and false-negative predictions, as well as any relevant clinical guidelines. To date, no studies have examined the impact of using early childhood obesity prediction models as intervention tools. While these are potentially valuable to inform targeted interventions, the heterogeneity of the existing models and the lack of consensus on adequate thresholds limit their usefulness in practice.
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| 41. |
- Chagin, AS, et al.
(författare)
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Androgen receptor modulation does not affect longitudinal growth of cultured fetal rat metatarsal bones
- 2009
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Ingår i: Hormone research. - : S. Karger AG. - 1423-0046. ; 71:4, s. 219-227
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Systemic administration of the nonaromatizable androgen oxandrolone stimulates growth in girls with Turner syndrome and boys with a constitutional delay of growth and puberty. It is unknown if oxandrolone acts locally at the growth plate level to stimulate longitudinal bone growth. <i>Methods:</i> Metatarsal bones from female and male rat fetuses (day E20) were cultured for 14 days in the presence of oxandrolone, testosterone or the androgen receptor (AR) antagonist flutamide with/without insulin-like growth-factor-I (IGF-I) or charcoal-treated serum. <i>Results:</i> The AR was found to be expressed in both male and female fetal rat metatarsal bones. Neither oxandrolone nor testosterone had any effect on metatarsal bone growth when tested at a wide concentration range (1 n<i>M</i> to 10 μ<i>M</i>), not even in the presence of IGF-I (100 ng/ml) or charcoal-treated serum (10%). Bone growth was also unaffected when the AR was blocked by flutamide. Control experiments confirmed that metatarsal bone growth was significantly stimulated by IGF-I (p < 0.001). <i>Conclusion:</i> Modulation of AR activity in the fetal rat growth plate does not affect linear bone growth. Extrapolating from these in vitro data, it could be speculated that oxandrolone stimulates longitudinal bone growth in treated children by acting indirectly rather than directly through AR activation in growth plate chondrocytes.
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| 42. |
- Chagin, AS, et al.
(författare)
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Genes of importance in the hormonal regulation of growth plate cartilage
- 2009
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Ingår i: Hormone research. - : S. Karger AG. - 1423-0046. ; 7171 Suppl 2, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Longitudinal bone growth occurs in the growth plate through a process in which resting zone chondrocytes are recruited to start active proliferation and then undergo differentiation, followed by apoptosis and later mineralization. Bone growth is controlled by a multitude of genes encoding for hormones and growth factors acting systemically and/or locally in the growth plate. From studies of individuals with a mutated aromatase gene and a male patient with defective oestrogen receptor (ER) α, it has become clear that the action of oestrogen is indispensable for normal pubertal growth and growth plate fusion. As new aromatase inhibitors and specific modulators of ERs are developed, these could offer more specific ways to modulate longitudinal growth and growth plate fusion. It is difficult to extrapolate data obtained in experimental animals, as clear species differences exist, emphasizing the need for new models that will allow studies in human growth plate cartilage.
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| 43. |
- 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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| 44. |
- Chaplin, John, 1955
(författare)
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Growth-related quality of life.
- 2011
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Ingår i: Hormone research in pædiatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 76 Suppl 3, s. 51-2
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Tidskriftsartikel (refereegranskat)abstract
- Measuring a child's quality of life (QoL) is a complex dynamic, involving consideration of both present circumstances and future limitations. In relation to short stature, health-related QoL, with its emphasis on current health status, may be inadequate to describe QoL in children with treatable growth problems. Growth problems concern not only current physical health (being) and adaptation to the physical and social environment (belonging) but also what will happen in the future as a consequence of growth problems and the possibility of achieving the potential of the individual (becoming). These three aspects of QoL should be included in growth-related QoL in order to reflect the reduced QoL resulting from continued short stature and the potential benefit of growth enhancement. Future QoL instruments for growth-related problems should incorporate aspects of 'becoming' and the long-term consequences of growth improvement for the individual.
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| 45. |
- 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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| 46. |
- Chaplin, John, 1955, et al.
(författare)
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When Do Short Children Realize They Are Short? : Prepubertal Short Children's Perception of Height during 24 Months of Catch-Up Growth Hormone Treatment
- 2012
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 77:4, s. 241-249
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children. Methods: Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children's and parents' responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height. Results: Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother's height, parental sense of the child's tallness and age explained more variance in children's sense of tallness (34%) than measured height (0%). Conclusion: Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short.
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| 47. |
- Chaychenko, T, et al.
(författare)
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Difference in Insulin Resistance Assessment between European Union and Non-European Union Obesity Treatment Centers (ESPE Obesity Working Group Insulin Resistance Project)
- 2021
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 93:11-12, s. 622-633
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The obesity epidemic has become one of the most important public health issues of modern times. Impaired insulin sensitivity seems to be the cornerstone of multiple obesity related comorbidities. However, there is no accepted definition of impaired insulin sensitivity. <b><i>Objective:</i></b> We hypothesize that assessment of insulin resistance differs between centers. <b><i>Methods:</i></b> The ESPE Obesity Working Group (ESPE ObWG) Scientific Committee developed a questionnaire with a focus on the routine practices of assessment of hyperinsulinemia and insulin resistance, which was distributed through Google Docs platform to the clinicians and researchers from the current ESPE ObWG database (<i>n</i> = 73). Sixty-one complete responses (84% response rate) from clinicians and researchers were analyzed: 32 from European Union (EU) centers (representatives of 14 countries) and 29 from Non-EU centers (representatives from 10 countries). Standard statistics were used for the data analysis. <b><i>Results:</i></b> The majority of respondents considered insulin resistance (IR) as a clinical tool (85.2%) rather than a research instrument. For the purpose of IR assessment EU specialists prefer analysis of the oral glucose tolerance test (OGTT) results, whereas non-EU ones mainly use Homeostatic Model Assessment of Insulin Resistance (HOMA-IR; <i>p</i> = 0.032). There was no exact cutoff for the HOMA-IR in either EU or non-EU centers. A variety of OGTT time points and substances measured per local protocol were reported. Clinicians normally analyzed blood glucose (88.52% of centers) and insulin (67.21%, mainly in EU centers, <i>p</i> = 0.0051). Furthermore, most participants (70.5%) considered OGTT insulin levels as a more sensitive parameter of IR than glucose. Meanwhile, approximately two-thirds (63.9%) of the centers did not use any cutoffs for the insulin response to the glucose load. <b><i>Conclusions:</i></b> Since there is no standard for the IR evaluation and uniform accepted indication of performing, an OGTT the assessment of insulin sensitivity varies between EU and non-EU centers. A widely accepted standardized protocol is needed to allow comparison between centers.
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| 48. |
- Chen, S. C., et al.
(författare)
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Development of A Minimum Dataset for the Monitoring of Recombinant Human Growth Hormone (rhGH) Therapy Use in Children with Growth Hormone Deficiency (GHD) - A GloBE-Reg Initiative
- 2023
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Ingår i: Hormone Research in Paediatrics. - 1663-2818 .- 1663-2826.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection. Methods This study was undertaken by the GH Scientific Study Group (SSG) in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with GHD was compiled. Each member was asked to determine the: (1) Importance of the data field and (2) Ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect.Results A total of 246 items were compiled and 27 removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GH deficiency (GHD) on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months and 9 every 12 months.Conclusion In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the minimum dataset requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting growth hormone.
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| 49. |
- Christesen, Henrik B. T., et al.
(författare)
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Rapid genetic analysis in congenital hyperinsulinism
- 2007
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Ingår i: Hormone Research. - : S. Karger AG. - 0301-0163. ; 67:4, s. 184-188
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Tidskriftsartikel (refereegranskat)abstract
- Backgound: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. Methods: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. Results: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. Conclusion: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations. Copyright (c) 2007 S. Karger AG, Basel.
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