Long‐term effects of growth hormone therapy on patients with Prader–Willi syndrome

Sipilä, Ilkka; Sintonen, Harri; Hietanen, Heikki; Apajasalo, M; Alanne, Soili; Viita, Anna-Mari; Leinonen, Eeva

doi:10.1111/j.1651-2227.2010.01904.x

Cited by 27 publications

(15 citation statements)

References 26 publications

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“…For clinical evidence in the pediatric population, randomized controlled trials (RCTs) (20–26, 33–41), comparative observational studies (42–48), and long-term studies (>3.5 y) (5, 49–58) were included. Adult studies included RCTs of rhGH treatment for ≥ 6 months (7, 29, 59, 60) and uncontrolled trials (61–64), because data were more limited.…”

Section: Workhop Methodologymentioning

confidence: 99%

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome

Deal

Tony

Höybye

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

331

418

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Context:Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in 2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events.Objective:The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS.Evidence:We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries.Methodology:Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN).Conclusions:Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.

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Section: Workhop Methodologymentioning

confidence: 99%

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome

Deal

Tony

Höybye

et al. 2013

The Journal of Clinical Endocrinology &Amp; Metabolism

331

418

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“…Exercise capacity was tested with broad jump, agility run, sit-ups, and upper arm strength assessments; the assessors were blinded to treatment status, and the treated group showed improvements compared to controls in all areas. Other studies have shown a persisting benefit to body fat but not to LBM, compared with ranges for normal children; the natural history of PWS is for increasing fat mass with age compared with normal children, so this probably still represents a benefit 18 19…”

Section: Trials Of Gh In Pwsmentioning

confidence: 99%

What is the value of growth hormone therapy in Prader Willi syndrome?

Bridges

2013

Archives of Disease in Childhood

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Prader Willi syndrome (PWS) is a genetic condition caused by loss of the paternal copy of a region of imprinted genes on chromosome 15. There is severe muscular hypotonia in the neonatal period, with the onset of hyperphagia and food-seeking behaviour in childhood. All individuals with PWS have developmental delay. Without careful control of food intake and the food environment, individuals with PWS become morbidly obese and are likely to die as young adults from the complications of obesity. The aims of growth hormone (GH) treatment in PWS are distinct from the use of GH in other conditions-although GH does increase final height in PWS, the main benefits of treatment are improved body composition and better exercise capacity, which can help with the aim of preventing obesity. GH trials in PWS have demonstrated improved muscle bulk, reduced fat mass and increased levels of physical activity. GH has also been demonstrated to improve attainment of developmental and cognitive milestones in children with PWS. GH treatment appears to change respiratory status in PWS, possibly because of growth of lymphoid tissue at the start of treatment. Respiratory assessment is recommended prior to, and just after starting GH treatment. Ideal age for starting GH is not clear, although there has been a trend towards starting at younger ages. It may be that GH treatment in childhood confers benefits into adult life. There are less data to support continuing GH treatment into adult life.

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“…This protective action of GH on EMT and consequent functional injury in podocytes was found to be due to blockade of the formation of membrane raft platforms with GHR and NADPH oxidase subunits and consequent O 2 .-production. Although there were reports that excessive endogenous production of GH as a peptide hormone secreted by the pituitary gland may be an injurious factor in pathogenesis of some diseases or pathological process such as diabetes mellitus and progressive glomerulosclerosis [24,25], this hormone is often used as a therapeutic agent for different medical conditions, some of which were approved by the U.S. Food and Drug Administration, such as cachexia [26], Turner syndrome [27], chronic renal failure [28], Prader-Willi syndrome [29], and idiopathic short stature (ISS) [30]. In addition to these and other therapeutic uses for improvement of growth in children or adults, GH has also been reported to be used for healing of large burns [31]or in obesity [32], Crohn's disease [33], chronic fatigue syndrome, aging [34] and various degenerative diseases such as Alzheimer's disease [35], multiple sclerosis [36], atherosclerosis [37] and chronic heart failure [38].…”

Section: Discussionmentioning

confidence: 99%

Reversal by Growth Hormone of Homocysteine-induced Epithelial-to-Mesenchymal Transition through Membrane Raft-Redox Signaling in Podocytes

Xia

Han

et al. 2011

Cell Physiol Biochem

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Epithelial-to-Mesenchymal Transition (EMT) is an important pathogenic mechanism mediating glomerular injury or sclerosis in a variety of renal and systemic diseases such as hyperhomocysteinemia (hHcys). The present study was designed to test whether Hcys-induced EMT in podocytes is reversed by growth hormone (GH), a hormone regulating cell differentiation and growth and to explore the cellular and molecular mechanism mediating its action. It was found that Hcys induced significant EMT in podocytes, as shown by marked decreases in slit diaphragm-associated protein P-cadherin and zonula occludens-1 as epithelial markers and by dramatic increases in the expression of mesenchymal markers, fibroblast specific protein-1 and α-smooth muscle actin, which were detected by all examinations via immunocytochemistry, real time RT-PCR and Western blot analysis. When podocytes were treated with GH at 25 ng/mL, however, Hcys failed to induce podocyte EMT. Using electromagnetic spin resonance spectrometry, Hcys-induced superoxide (O₂.^-) production via NADPH oxidase was found to be significantly inhibited by GH (66%). Functionally, GH was shown to substantially inhibit Hcys-induced increases in the permeability of podocyte monolayers and to block the decrease in podocin expression in these cells. In addition, NADPH oxidase subunit, gp91^phox and GH receptors aggregated in membrane raft clusters, which produced O₂.^- in response to Hcys and could be blocked by GH, membrane raft disruptors filipin and MCD or NADPH oxidase inhibitor, apocynin. It is concluded that Hcys-induced podocyte EMT is associated with transmembrane membrane raft-redox signaling and that GH reverses this Hcys-induced EMT protecting podocytes from functional disturbance.

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Long‐term effects of growth hormone therapy on patients with Prader–Willi syndrome

Abstract: Growth hormone markedly improved adult height in subjects with PWS when compared to historical data. The cumulative dose of growth hormone correlated with reduction in body fat; nevertheless, patients remained severely obese.

Cited by 27 publications

References 26 publications

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome

Growth Hormone Research Society Workshop Summary: Consensus Guidelines for Recombinant Human Growth Hormone Therapy in Prader-Willi Syndrome

What is the value of growth hormone therapy in Prader Willi syndrome?

Reversal by Growth Hormone of Homocysteine-induced Epithelial-to-Mesenchymal Transition through Membrane Raft-Redox Signaling in Podocytes

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