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Hormone Research in Paediatrics 2016On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in 2003 on the use of...
Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency.
BACKGROUND/AIMS
On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in 2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS) remains a controversial indication, and diagnostic challenges often blur the distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I therapy to the GH guidelines for the first time.
METHODS
This guideline was developed following the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation).
RESULTS
This guideline provides recommendations for the clinical management of children and adolescents with growth failure from GHD, ISS, or PIGFD using the best available evidence.
CONCLUSION
The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient. In many instances, careful review highlights areas that need further research.
Topics: Adolescent; Child; Child, Preschool; Female; Growth Disorders; Human Growth Hormone; Humans; Infant; Insulin-Like Growth Factor I; Male
PubMed: 27884013
DOI: 10.1159/000452150 -
Hormone Research in Paediatrics 2019The 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... (Review)
Review
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.
Topics: Child; Growth Disorders; Human Growth Hormone; Humans
PubMed: 31514194
DOI: 10.1159/000502231 -
Cells Jun 2021Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body... (Review)
Review
Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body maintenance, and in conditions of energy deprivation, favor catabolic feedback mechanisms switching from carbohydrate oxidation to lipolysis, with the aim to preserve protein storages and survival. IGF-I/insulin signaling was also the first one identified in the regulation of lifespan in relation to the nutrient-sensing. Indeed, nutrients are crucial modifiers of the GH/IGF-I axis, and these hormones also regulate the complex orchestration of utilization of nutrients in cell and tissues. The aim of this review is to summarize current knowledge on the reciprocal feedback among the GH/IGF-I axis, macro and micronutrients, and dietary regimens, including caloric restriction. Expanding the depth of information on this topic could open perspectives in nutrition management, prevention, and treatment of GH/IGF-I deficiency or excess during life.
Topics: Caloric Restriction; Carbohydrate Metabolism; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Lipolysis; Micronutrients; Signal Transduction
PubMed: 34199514
DOI: 10.3390/cells10061376 -
Nature Reviews. Endocrinology May 2018Growth hormone (GH) research and its clinical application for the treatment of growth disorders span more than a century. During the first half of the 20th century,... (Review)
Review
Growth hormone (GH) research and its clinical application for the treatment of growth disorders span more than a century. During the first half of the 20th century, clinical observations and anatomical and biochemical studies formed the basis of the understanding of the structure of GH and its various metabolic effects in animals. The following period (1958-1985), during which pituitary-derived human GH was used, generated a wealth of information on the regulation and physiological role of GH - in conjunction with insulin-like growth factors (IGFs) - and its use in children with GH deficiency (GHD). The following era (1985 to present) of molecular genetics, recombinant technology and the generation of genetically modified biological systems has expanded our understanding of the regulation and role of the GH-IGF axis. Today, recombinant human GH is used for the treatment of GHD and various conditions of non-GHD short stature and catabolic states; however, safety concerns still accompany this therapeutic approach. In the future, new therapeutics based on various components of the GH-IGF axis might be developed to further improve the treatment of such disorders. In this Review, we describe the history of GH research and clinical use with a particular focus on disorders in childhood.
Topics: Female; Growth Hormone; Human Growth Hormone; Humans; Male; Somatomedins
PubMed: 29546874
DOI: 10.1038/nrendo.2018.22 -
International Journal of Molecular... Dec 2021Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of... (Review)
Review
Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of the hypothalamic-pituitary-thyroid axis, and even generate melatonin and prolactin, human hair research has proven to be a treasure chest for the exploration of neurohormone functions. However, growth hormone (GH), one of the dominant neurohormones of human neuroendocrine physiology, remains to be fully explored in this context. This is interesting since it has long been appreciated clinically that excessive GH serum levels induce distinct human skin pathology. Acromegaly, or GH excess, is associated with hypertrichosis, excessive androgen-independent growth of body hair, and hirsutism in females, while dysfunctional GH receptor-mediated signaling (Laron syndrome) is associated with alopecia and prominent HF defects. The outer root sheath keratinocytes have recently been shown to express functional GH receptors. Furthermore, and contrary to its name, recombinant human GH is known to inhibit female human scalp HFs' growth ex vivo, likely via stimulating the expression of the catagen-inducing growth factor, TGF-β2. These limited available data encourage one to systematically explore the largely uncharted role of GH in human HF biology to uncover nonclassical functions of this core neurohormone in human skin physiology.
Topics: Female; Hair Follicle; Human Growth Hormone; Humans; Receptors, Somatotropin; Skin
PubMed: 34948002
DOI: 10.3390/ijms222413205 -
Sports Health 2018Recombinant human growth hormone (rHGH) has become a target of abuse in the sporting world. Conversely, sports medicine clinicians may encounter athletes using rHGH to... (Review)
Review
CONTEXT
Recombinant human growth hormone (rHGH) has become a target of abuse in the sporting world. Conversely, sports medicine clinicians may encounter athletes using rHGH to achieve normalcy in the context of growth hormone (GH) deficiency.
EVIDENCE ACQUISITION
Medline and PubMed databases were queried using the following keywords: GH, GH physiology, GH deficiency, acromegaly, GH athlete, GH sports, GH athletic performance, and GH deficiency concussion. Articles focusing on GH physiology, deficiency, excess, and its effects in both deficient and healthy patients were included.
STUDY DESIGN
Clinical review.
LEVEL OF EVIDENCE
Level 3.
RESULTS
GH is a naturally occurring hormone with important roles in human physiology. Patients with GH deficiency (GHD) present variably, and GHD has numerous etiologies. rHGH treatment has substantial therapeutic benefits for patients with GHD. The benefits of rHGH treatment in otherwise-healthy adults are uncertain. GH excess may cause health problems such as acromegaly. Professional, collegiate, and international sports leagues and associations have banned rHGH use to maintain athlete health, safety, and fair play. Athletes misusing GH may face prolonged suspensions from competition. Implementing GH abuse testing is challenging, but new methods, such as the biomarker testing procedure, are being finalized.
CONCLUSION
rHGH is not only an important therapeutic agent for GH-deficient patients but also a target of abuse in competitive athletics. Its benefits in a healthy, adult population are uncertain. A safe exercise and competition plan, developed with a physician knowledgeable of GH use, physiology, and abuse potential, should be of benefit to a longitudinal clinician-patient relationship.
Topics: Athletic Performance; Body Composition; Brain Concussion; Competitive Behavior; Counseling; Doping in Sports; Human Growth Hormone; Humans; Off-Label Use; Recombinant Proteins; Recurrence; Substance Abuse Detection
PubMed: 29932857
DOI: 10.1177/1941738118782688 -
Frontiers in Endocrinology 2021The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19 century. Its non-acquired variant (naGHD) is,... (Review)
Review
The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19 century. Its non-acquired variant (naGHD) is, at childhood onset, a rare syndrome of multiple etiologies, predominantly characterized by severe and permanent growth failure culminating in short stature. It is still difficult to diagnose GHD and, in particular, to ascertain impaired GH secretion in comparison to levels in normally-growing children. The debate on what constitutes an optimal diagnostic process continues. Treatment of the GH deficit replacement with cadaveric pituitary human GH (pit-hGH) had first been demonstrated in 1958, and opened an era of therapeutic possibilities, albeit for a limited number of patients. In 1985, the era of recombinant hGH (r-hGH) began: unlimited supply meant that substantial long-term experience could be gained, with greater focus on efficacy, safety and costs. However, even today, the results of current treatment regimes indicate that there is still a substantial fraction of children who do not achieve adult height within the normal range. Renewed evaluation of height outcomes in childhood-onset naGHD is required for a better understanding of the underlying causes, whereby the role of various factors - diagnostics, treatment modalities, mode of treatment evaluation - during the important phases of child growth - infancy, childhood and puberty - are further explored.
Topics: Adolescent; Body Height; Child; Child Development; Dwarfism, Pituitary; Growth Disorders; History, 19th Century; History, 20th Century; History, 21st Century; Hormone Replacement Therapy; Human Growth Hormone; Humans; Puberty; Time Factors
PubMed: 34539573
DOI: 10.3389/fendo.2021.720419 -
The Journal of Clinical Endocrinology... Feb 2022The use of recombinant human growth hormone (rhGH) in children and adolescents has expanded since its initial approval to treat patients with severe GH deficiency (GHD)... (Review)
Review
The use of recombinant human growth hormone (rhGH) in children and adolescents has expanded since its initial approval to treat patients with severe GH deficiency (GHD) in 1985. rhGH is now approved to treat several conditions associated with poor growth and short stature. Recent studies have raised concerns that treatment during childhood may affect morbidity and mortality in adulthood, with specific controversies over cancer risk and cerebrovascular events. We will review 3 common referrals to a pediatric endocrinology clinic, followed by a summary of short- and long-term effects of rhGH beyond height outcomes. Methods to mitigate risk will be reviewed. Finally, this information will be applied to each clinical case, highlighting differences in counseling and clinical outcomes. rhGH therapy has been used for more than 3 decades. Data are largely reassuring, yet we still have much to learn about pharmaceutical approaches to growth in children and the lifelong effect of treatment.
Topics: Adolescent; Child; Counseling; Female; Growth Disorders; Hormone Replacement Therapy; Human Growth Hormone; Humans; Male; Recombinant Proteins; Treatment Outcome
PubMed: 34636896
DOI: 10.1210/clinem/dgab746 -
American Journal of Health-system... Nov 2023
Topics: Humans; Human Growth Hormone
PubMed: 37703102
DOI: 10.1093/ajhp/zxad209 -
The Journal of Clinical Endocrinology... Oct 2021For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD.
OBJECTIVE
The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin.
DESIGN
The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3 trial (NCT02781727).
SETTING
This trial took place at 73 sites across 15 countries.
PATIENTS
This trial enrolled and dosed 161 treatment-naïve, prepubertal patients with GHD.
INTERVENTIONS
Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily.
MAIN OUTCOME MEASURE
The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS).
RESULTS
Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups.
CONCLUSIONS
The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.
Topics: Child; Dwarfism, Pituitary; Female; Follow-Up Studies; Hormone Replacement Therapy; Human Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Prognosis
PubMed: 34272849
DOI: 10.1210/clinem/dgab529