| 1. |
- Christiansen, J. S., et al.
(författare)
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Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
- 2016
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
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| 2. |
- Allen, D. B., et al.
(författare)
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GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults
- 2016
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:2
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 3. |
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| 4. |
- Collett-Solberg, Paulo F., et al.
(författare)
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Diagnosis, Genetics, and Therapy of Short Stature in Children : A Growth Hormone Research Society International Perspective
- 2019
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 92:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
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| 5. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth Hormone Research Society perspective on biomarkers of GH action in children and adults
- 2018
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
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| 6. |
- Boguszewski, C. L., et al.
(författare)
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Mechanisms in endocrinology: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism
- 2017
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Ingår i: European Journal of Endocrinology. - 0804-4643. ; 177:6
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system. As the first genetic variant to potentially influence the individual response to rhGH therapy in children with growth disorders, polymorphism in the GH receptor (GHR) has attracted a great interest as a target for pharmacogenetics. Studies have been conducted to compare the functional and molecular effects of the full-length GHR (fl-GHR) isoform with the exon 3 deleted (d3-GHR) isoform in children and adults treated with rhGH therapy. Additionally, the impact of the GHR polymorphism has been investigated in relation to the clinical status and response to medical treatment in acromegaly, especially to the GHR antagonist drug pegvisomant. We have performed a narrative review of the studies performed to date on the association of GHR polymorphism with rhGH response in children and adults, and its potential influence in the medical management of acromegaly. In addition, data from studies on the general population and in other chronic diseases examining a role of this genetic variant in the regulation of growth and metabolism are summarized. © 2017 European Society of Endocrinology.
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| 7. |
- Sakellariou, P., et al.
(författare)
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Chronic L-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health
- 2016
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Ingår i: Medical Hypotheses. - : Elsevier BV. - 0306-9877. ; 93, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT. Hypothesis: Recent evidence support a role of L-menthol cooling, mediated by TRPM8 receptor, on UCP1-dependent thermogenesis and BAT-like activity in classical WAT depots along with the recruitment of BAT at specific anatomical sites. L-Menthol-induced BAT thermogenesis has been suggested to occur by a beta-adrenergic-independent mechanism, avoiding potential side-effects due to extensive beta-adrenergic stimulation mediated by available beta receptor agonists. L-Menthol has been also linked to the activation of the cold-gated ion channel TRPA1. However, its role in L-menthol-induced UCP1-dependent thermogenic activity in BAT and WAT remains undetermined. White adipose tissue plasticity has important clinical implications for obesity prevention and/or treatment because higher levels of UCP1-dependent thermogenesis can lead to enhanced energy expenditure at a considerable extent. We hypothesize that chronic dietary L-menthol treatment could induce TRPM8- and TRPA1-dependent WAT adaptations, resembling BAT-like activity, and overall improve whole-body metabolic health in obese and overweight individuals. Conclusions: The putative impact of chronic L-menthol dietary treatment on the stimulation of BAT-like activity in classical WAT depots in humans remains unknown. A detailed experimental design has been proposed to investigate the hypothesized L-menthol-induced browning of WAT. If our hypothesis was to be confirmed, TRPM8/TRPA1-induced metabolic adaptations of WAT to BAT-like activity could provide a promising novel therapeutic approach for increasing energy expenditure, regulating body weight, and preventing obesity and its related co-morbidities in humans. (C) 2016 Elsevier Ltd. All rights reserved.
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| 8. |
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| 9. |
- Schilbach, K., et al.
(författare)
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Biomarkers of GH action in children and adults
- 2018
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 40, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) and IGF-I levels in serum are used as biomarkers in the diagnosis and management of GH-related disorders but have not been subject to structured validation. Auxological parameters in children and changes in body composition in adults, as well as metabolic parameters and patient related outcomes are used as clinical and surrogate endpoints. New treatment options, such as long acting GH and GH antagonists, require reevaluation of the currently used biochemical biomarkers. This article will review biomarkers, surrogate endpoints and clinical endpoints related to GH treatment in children and adults as well as in acromegaly. © 2018 Elsevier Ltd
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