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Anita C. S. Hokken-koelega - One of the best experts on this subject based on the ideXlab platform.
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Three years of Growth Hormone Treatment in young adults with Prader-Willi syndrome: sustained positive effects on body composition.
Orphanet journal of rare diseases, 2020Co-Authors: Layla Damen, L.c.g. De ,graaff, Stephany Donze, Renske Kuppens, Nienke Bakker, Janiëlle A E M Van Der Velden, Anita C. S. Hokken-koelegaAbstract:Background: In children with Prader-Willi syndrome (PWS), the benefits of Growth Hormone Treatment are well established. Several one-year studies have shown that Growth Hormone is also beneficial for adults with PWS, improving body composition. However, little is known about the longer-term effects. This study investigated the effects on body composition in adult patients with PWS during 3 years of Growth Hormone therapy in a dose of 0.33 mg/m2/day. Methods: Open-label, prospective study in 43 young adults with PWS with a median (IQR) age of 19.0 (17.5 to 20.7) years. Fat mass percentage SDS and lean body mass SDS were measured annually by DXA. Results: Estimated mean (95% CI) fat mass percentage SDS decreased during the three-year study from 2.1 (1.9 to 2.3) SDS at start to 1.9 (1.8 to 2.1) SDS, p = 0.012, while lean body mass SDS remained stable at - 2.1 (- 2.4 to - 1.8) SDS at start to - 1.9 (- 2.3 to - 1.6) after 3 years, p = 0.15. Fasting glucose and insulin remained similar during the three-year study, glucose being 4.6 (4.4 to 4.8) mmol/l at start and 4.6 (4.5 to 4.7) mmol/l after 3 years of Growth Hormone, p = 0.93 and insulin being 59.5 (42.2 to 81.5) pmol/l and 55.0 (42.4 to 69.2) pmol/l, resp., p = 0.54. There were no Growth Hormone-related adverse events during the study. Conclusions: Three years of Growth Hormone Treatment in young adults with PWS maintains the positive effects on body composition attained during childhood. Thus, adults with PWS benefit from longer-term Growth Hormone Treatment. Trial registration: EudraCT, EudraCT number 2011-001313-14. Registered 17 October 2012.
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Cardiovascular risk factors and carotid intima media thickness in young adults born small for gestational age after cessation of Growth Hormone Treatment: a 5-year longitudinal study
The lancet. Diabetes & endocrinology, 2017Co-Authors: Manouk Van Der Steen, Carolina C J Smeets, Gerthe F. Kerkhof, Anita C. S. Hokken-koelegaAbstract:Summary Background Growth Hormone Treatment reduces blood pressure and lipid concentrations. We assessed long-term changes in blood pressure, lipid concentrations, and carotid intima media thickness over a 5-year period after cessation of Growth Hormone Treatment in adults born small for gestational age. Methods We did a longitudinal observational study at a medical centre in the Netherlands between April 1, 2004, and April 1, 2016. We included adults born small for gestational age who were treated with Growth Hormone (1 mg/m 2 per day); Treatment started during childhood until adult height. Participants were evaluated at cessation of Treatment, and 6 months, 2 years, and 5 years later. We compared cardiovascular risk factors with untreated controls from the PROGRAM study. Findings We included 199 participants born small for gestational age and treated with Growth Hormone along with 285 controls: 51 untreated short adults born small for gestational age, 92 untreated adults born small for gestational age with spontaneous catch-up Growth, and 142 adults born appropriate for gestational age. In the 6 months after Treatment cessation, systolic blood pressure increased temporarily from 113·00 mm Hg (95% CI 111·18–114·82) to 116·92 mm Hg (115·07 to 118·77; p vs 2·85 mmol/L, 2·62–3·10; p 0·12). At 5 years after cessation, systolic blood pressure, diastolic blood pressure, lipid concentrations, and carotid intima media thickness of adults treated with Growth Hormone were not different to those in adults born small for gestational age who had spontaneous catch-up Growth or adults born appropriate for gestational age. Interpretation Long-term Growth Hormone Treatment in children born small for gestational age has no unfavourable effects on cardiovascular health in early adulthood and improves lipid profiles. Funding Novo Nordisk (Netherlands).
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Metabolic health of young adults who were born small for gestational age and treated with Growth Hormone, after cessation of Growth Hormone Treatment: a 5-year longitudinal study
The lancet. Diabetes & endocrinology, 2016Co-Authors: Manouk Van Der Steen, Carolina C J Smeets, Gerthe F. Kerkhof, Anita C. S. Hokken-koelegaAbstract:Summary Background Growth Hormone Treatment reduces fat mass and insulin sensitivity and increases lean body mass. Data are only available for short-term longitudinal changes after cessation of Growth Hormone Treatment in young adults born small for gestational age. We aimed to assess long-term changes over a 5-year period following cessation of Growth Hormone Treatment. Methods We did a longitudinal study of young adults born small for gestational age and previously treated with Growth Hormone. Individuals were followed up for 5 years after attainment of adult height, when Growth Hormone Treatment was discontinued: assessments were done at cessation of Growth Hormone Treatment and at 6 months, 2 years, and 5 years thereafter. Data 5 years after cessation of Growth Hormone were compared with untreated age-matched controls. We used dual-energy x-ray absorptiometry to assess body composition, and did frequently sampled intravenous glucose tolerance tests to assess insulin sensitivity, acute insulin response, and the disposition index (a measure of β-cell function). This study is registered with ISRCTN, numbers ISRCTN96883876 and ISRCTN65230311. Findings Between April, 2004, and April, 2016, we followed up 199 young adults born small for gestational age and previously treated with Growth Hormone, during the 5 years after cessation of Growth Hormone Treatment. Data at 5 years for these individuals were compared with those for 51 untreated adults born small for gestational age with short stature, 92 untreated adults born small for gestational age with spontaneous catch-up Growth, and 142 adults born appropriate for gestational age and unexposed to Growth Hormone Treatment. In young adults born small for gestational age and previously treated with Growth Hormone, 5 years after cessation of Growth Hormone Treatment, there were increases in fat mass (estimated marginal mean 10·73 kg [95% CI 9·95–11·50] at cessation of Treatment vs 16·12 kg [14·77–17·46] at 5 years; p vs 7·86 kg [7·12–8·60]; p vs 7·41 kg [6·78–8·05]; p vs 41·42 kg [40·17–42·66] at 5 years; p=0·0013). Insulin sensitivity increased within 6 months of cessation and was sustained 5 years after Treatment cessation (estimated marginal mean 4·14 mU/L [95% CI 3·79–4·53] at cessation of Treatment vs 6·15 mU/L [5·21–7·24] at 5 years; p vs 393·69 mU/L [337·56–459·15]; p vs 2367·83 [2033·43–2757·22] at 5 years; p=0·49). 5 years after cessation of Growth Hormone Treatment, adults born small for gestational age and previously treated with Growth Hormone had fat mass, insulin sensitivity, and disposition index similar to those of untreated adults born small for gestational age with short stature, but lean body mass (adjusted for sex and height) was lower (46·47 kg [44·95–48·00] in those born small for gestational age with short stature vs 44·32 kg [43·35–45·30] in those born small for gestational age and treated with Growth Hormone; p=0·007). In adults previously treated with Growth Hormone born small for gestational age, at 5 years after cessation of Growth Hormone Treatment, compared with adults born small for gestational age with spontaneous catch-up Growth and adults born appropriate for gestational age, lean body mass was lower and results from frequently sampled intravenous glucose tolerance tests were similar. Interpretation Significant changes in body composition and insulin sensitivity were recorded 5 years after cessation of Growth Hormone Treatment in adults born small for gestational age, reflecting a loss of pharmacological effects of Growth Hormone. 5 years after cessation of Treatment, fat mass, insulin sensitivity, and β-cell function of previously treated adults were similar to untreated adults born small for gestational age with short stature, indicating that long-term Growth Hormone Treatment in children born small for gestational age has no unfavourable effects on metabolic health in early adulthood. Funding Novo Nordisk Farma BV (Netherlands).
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Beneficial Effects of Long-Term Growth Hormone Treatment on Adaptive Functioning in Infants With Prader-Willi Syndrome.
American journal on intellectual and developmental disabilities, 2015Co-Authors: Dederieke A. M. Festen, Roderick F. A. Tummers-de Lind Van Wijngaarden, Philippe Collin, Anita C. S. Hokken-koelegaAbstract:Abstract The aim of this study was to investigate the effect of Growth Hormone Treatment on adaptive functioning in children with Prader-Willi syndrome. Vineland Adaptive Behavior Scale (VABS) was assessed during a randomized controlled trial (RCT) and after 7 years of Growth Hormone Treatment. In the RCT, 75 children (42 infants and 33 prepubertal children) with Prader-Willi syndrome were included. Subsequently, 53 children were treated with long-term Growth Hormone. Our study demonstrates a marked delay in adaptive functioning in infants and children with Prader-Willi syndrome, which was associated with older age and lower intelligence. Results of the repeated measurements show that the earlier Growth Hormone Treatment was started during infancy, the better the adaptive skills were on the long-term.
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Breathing disorders in Prader–Willi syndrome: the role of obesity, Growth Hormone Treatment and upper respiratory tract infections
Expert review of endocrinology & metabolism, 2007Co-Authors: Dederieke A. M. Festen, Anita C. S. Hokken-koelegaAbstract:Prader-Willi syndrome is a neurogenetic disorder characterized by a number of signs and symptoms, including muscular hypotonia in infancy, hypogonadism, obesity and short stature. Neurobehavioral abnormalities and cognitive impairment are common. In addition, breathing abnormalities have been described, including sleep-related breathing disorders, abnormal chemoreceptor sensitivity and pulmonary function abnormalities. Growth Hormone Treatment is now widely used in children with Prader-Willi syndrome to improve Growth and body composition. Over the last 4 years, case reports have been published concerning unexpected death, many of which were related to respiratory abnormalities. This review focuses on breathing abnormalities in Prader-Willi syndrome individuals and the influence of obesity, Growth Hormone Treatment and upper respiratory tract infections.
Otto Mehls - One of the best experts on this subject based on the ideXlab platform.
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Growth Hormone Treatment after renal transplantation: a promising but underused chance to improve Growth
Pediatric Nephrology, 2013Co-Authors: Otto Mehls, Richard N. FineAbstract:Growth retardation remains a clinical problem in children with chronic kidney disease (CKD) prior to and during end-stage renal disease. The Growth of approximately 40 % of children on dialysis is stunted. Even so, Growth Hormone Treatment (GH) is not used in the majority of small children prior to transplantation. Also, GH is effective in improving Growth after transplantation, but again, it is only rarely used in this situation mainly for fear of triggering rejection episodes. In controlled studies, the number of patients who developed rejection episodes with GH was no greater than the number in untreated controls. However, patients with prior frequent rejection episodes developed further repeated subsequent rejection episodes. Many patients with repeated rejection episodes before GH Treatment have reduced renal function and are expected to proceed to dialysis or retransplantation. We believe that in these patients, early individual decisions for or against GH Treatment should be made as soon as other Treatment strategies, such as steroid withdrawal, have failed or are not indicated. Decisions for GH Treatment at a later pubertal age come too late for significant Growth response and/or improvement of final height.
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effect of Growth Hormone Treatment on the adult height of children with chronic renal failure
The New England Journal of Medicine, 2000Co-Authors: Dieter Haffner, Burkhard Tönshoff, Franz Schaefer, Richard Nissel, Elke Wuhl, Otto MehlsAbstract:Background Growth Hormone Treatment stimulates Growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. Methods We followed 38 initially prepubertal children with chronic renal failure treated with Growth Hormone for a mean of 5.3 years until they reached their final adult height. The mean (±SD) age at the start of Treatment was 10.4±2.2 years, the mean bone age was 7.1±2.3 years, and the mean height was 3.1±1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with Growth Hormone served as controls. Results The children treated with Growth Hormone had sustained catch-up Growth, whereas the control children had progressive Growth failure. The mean final height of the Growth Hormone–treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the Growth Hormone–treated children was 1.6±1.2 SD below normal, which was 1.4 SD above their standardized height at bas...
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Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience
Kidney international, 1993Co-Authors: Burkhard Tönshoff, Udo Heinrich, Dieter Haffner, Otto Mehls, Melanie Dietz, Hans Ruder, Werner F. Blum, B. StöverAbstract:Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience. The majority of children with renal allografts have diminished Growth and reduced final height. Impaired allograft function and glucocorticoid Treatment are the main contributing factors. Since recombinant human Growth Hormone (rhGH) Treatment was able to counteract the Growth depressing effects of glucocorticoids in experimental uremia, an open-labeled prospective study in 17 short children with renal allografts was designed to investigate the efficacy of rhGH therapy (30 IU/m 2 /week) with special emphasis on the safety regarding graft function and carbohydrate metabolism. Height velocity in prepubertal children (N = 10) increased from baseline median 2.2 cm/year to 7.9 cm/year after one year (P
Burkhard Tönshoff - One of the best experts on this subject based on the ideXlab platform.
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effect of Growth Hormone Treatment on the adult height of children with chronic renal failure
The New England Journal of Medicine, 2000Co-Authors: Dieter Haffner, Burkhard Tönshoff, Franz Schaefer, Richard Nissel, Elke Wuhl, Otto MehlsAbstract:Background Growth Hormone Treatment stimulates Growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. Methods We followed 38 initially prepubertal children with chronic renal failure treated with Growth Hormone for a mean of 5.3 years until they reached their final adult height. The mean (±SD) age at the start of Treatment was 10.4±2.2 years, the mean bone age was 7.1±2.3 years, and the mean height was 3.1±1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with Growth Hormone served as controls. Results The children treated with Growth Hormone had sustained catch-up Growth, whereas the control children had progressive Growth failure. The mean final height of the Growth Hormone–treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the Growth Hormone–treated children was 1.6±1.2 SD below normal, which was 1.4 SD above their standardized height at bas...
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Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience
Kidney international, 1993Co-Authors: Burkhard Tönshoff, Udo Heinrich, Dieter Haffner, Otto Mehls, Melanie Dietz, Hans Ruder, Werner F. Blum, B. StöverAbstract:Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience. The majority of children with renal allografts have diminished Growth and reduced final height. Impaired allograft function and glucocorticoid Treatment are the main contributing factors. Since recombinant human Growth Hormone (rhGH) Treatment was able to counteract the Growth depressing effects of glucocorticoids in experimental uremia, an open-labeled prospective study in 17 short children with renal allografts was designed to investigate the efficacy of rhGH therapy (30 IU/m 2 /week) with special emphasis on the safety regarding graft function and carbohydrate metabolism. Height velocity in prepubertal children (N = 10) increased from baseline median 2.2 cm/year to 7.9 cm/year after one year (P
Dieter Haffner - One of the best experts on this subject based on the ideXlab platform.
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effect of Growth Hormone Treatment on the adult height of children with chronic renal failure
The New England Journal of Medicine, 2000Co-Authors: Dieter Haffner, Burkhard Tönshoff, Franz Schaefer, Richard Nissel, Elke Wuhl, Otto MehlsAbstract:Background Growth Hormone Treatment stimulates Growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. Methods We followed 38 initially prepubertal children with chronic renal failure treated with Growth Hormone for a mean of 5.3 years until they reached their final adult height. The mean (±SD) age at the start of Treatment was 10.4±2.2 years, the mean bone age was 7.1±2.3 years, and the mean height was 3.1±1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with Growth Hormone served as controls. Results The children treated with Growth Hormone had sustained catch-up Growth, whereas the control children had progressive Growth failure. The mean final height of the Growth Hormone–treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the Growth Hormone–treated children was 1.6±1.2 SD below normal, which was 1.4 SD above their standardized height at bas...
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Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience
Kidney international, 1993Co-Authors: Burkhard Tönshoff, Udo Heinrich, Dieter Haffner, Otto Mehls, Melanie Dietz, Hans Ruder, Werner F. Blum, B. StöverAbstract:Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience. The majority of children with renal allografts have diminished Growth and reduced final height. Impaired allograft function and glucocorticoid Treatment are the main contributing factors. Since recombinant human Growth Hormone (rhGH) Treatment was able to counteract the Growth depressing effects of glucocorticoids in experimental uremia, an open-labeled prospective study in 17 short children with renal allografts was designed to investigate the efficacy of rhGH therapy (30 IU/m 2 /week) with special emphasis on the safety regarding graft function and carbohydrate metabolism. Height velocity in prepubertal children (N = 10) increased from baseline median 2.2 cm/year to 7.9 cm/year after one year (P
B. Stöver - One of the best experts on this subject based on the ideXlab platform.
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Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience
Kidney international, 1993Co-Authors: Burkhard Tönshoff, Udo Heinrich, Dieter Haffner, Otto Mehls, Melanie Dietz, Hans Ruder, Werner F. Blum, B. StöverAbstract:Efficacy and safety of Growth Hormone Treatment in short children with renal allografts: Three year experience. The majority of children with renal allografts have diminished Growth and reduced final height. Impaired allograft function and glucocorticoid Treatment are the main contributing factors. Since recombinant human Growth Hormone (rhGH) Treatment was able to counteract the Growth depressing effects of glucocorticoids in experimental uremia, an open-labeled prospective study in 17 short children with renal allografts was designed to investigate the efficacy of rhGH therapy (30 IU/m 2 /week) with special emphasis on the safety regarding graft function and carbohydrate metabolism. Height velocity in prepubertal children (N = 10) increased from baseline median 2.2 cm/year to 7.9 cm/year after one year (P
