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Frontiers in Endocrinology 2021Growth hormone (GH), once the age of linear growth is completed, continues to play a fundamental role for the human body. In adulthood, GH contributes to regulate... (Review)
Review
Growth hormone (GH), once the age of linear growth is completed, continues to play a fundamental role for the human body. In adulthood, GH contributes to regulate muscle, cardiovascular and bone metabolism. The same happens in old age, although there is less data on the effect of GH in the elderly. Regardless the age of onset, a reduced quality of life (QoL), an increased cardiovascular risk and an accelerated age-related decline in physical strength have been demonstrated in the elderly with GH deficiency (EGHD). In adults with GH deficiency (AGHD), recent studies suggest a role of GH replacement therapy (GHrt) in improving lean/fat mass ratio, blood pressure, lipid profile, bone metabolism and QoL. Despite these recent studies, there is still a lack of randomized controlled trials proving these positive effects in EGHD. Moreover, the lack of a long-term positive outcome on mortality, and the cost of GHrt could often impact on treatment decision-making and lead to postpone or avoid the prescription. The aim of this mini-review is to summarize the available data on GHrt in EGHD, in order to highlight its weaknesses and strengths and to provide directions to clinicians that will help in the management of this specific set of patients.
Topics: Aged; Body Composition; Cognition; Hormone Replacement Therapy; Human Growth Hormone; Humans; Muscle Strength; Quality of Life
PubMed: 34211437
DOI: 10.3389/fendo.2021.680579 -
Archives of Endocrinology and Metabolism 2019GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing... (Review)
Review
GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91.
Topics: Animals; Glucose; Human Growth Hormone; Humans; Insulin Resistance; Signal Transduction
PubMed: 31939483
DOI: 10.20945/2359-3997000000188 -
Archives of Disease in Childhood Oct 1963
Topics: 17-Ketosteroids; Adrenal Cortex Hormones; Growth Hormone; Human Growth Hormone; Humans; Infant; Lipodystrophy; Lipodystrophy, Congenital Generalized; Metabolism
PubMed: 14065985
DOI: 10.1136/adc.38.201.447 -
The Journal of Clinical Endocrinology... Jun 2013GH secretion is controlled by hypothalamic as well as intrapituitary and peripheral signals, all of which converge upon the somatotroph, resulting in integrated GH... (Review)
Review
GH secretion is controlled by hypothalamic as well as intrapituitary and peripheral signals, all of which converge upon the somatotroph, resulting in integrated GH synthesis and secretion. Enabling an accurate diagnosis of idiopathic adult GH deficiency (IAGHD) is challenged by the pulsatility of GH secretion, provocative test result variability, and suboptimal GH assay standardization. The spectrum between attenuated GH secretion associated with the normal aging process and with obesity and truly well-defined IAGHD is not distinct and may mislead the diagnosis. Adult-onset GHD is mainly caused by an acquired pituitary deficiency, commonly including prior head/neck irradiation, or an expanding pituitary mass causing functional somatotroph compression. To what extent rare cryptic causes account for those patients seemingly classified as IAGHD is unclear. About 15% of patients with adult GHD and receiving GH replacement in open-label surveillance studies are reported as being due to an idiopathic cause. These patients may also reflect a pool of subjects with an as yet to be determined occult defect, or those with unclear or incomplete medical histories (including forgotten past sports head injury or motor vehicle accident). Therefore, submaximal diagnostic evaluation likely leads to an inadvertent diagnosis of IAGHD. In these latter cases, adherence to rigorous biochemical diagnostic criteria and etiology exclusion may result in reclassification of a subset of these patients to a distinct known acquired etiology, or as GH-replete. Accordingly, rigorously verified IAGHD likely comprises less than 10% of adult GHD patients, an already rare disorder. Regardless of etiology, patients with adult GHD, including those with IAGHD, exhibit a well-defined clinical phenotype including increased fat mass, loss of lean muscle mass, decreased bone mass, and enhanced cardiac morbidity. Definition of unique efficacy and dosing parameters for GH replacement and resultant therapeutic efficacy markers in true IAGHD requires prospective study.
Topics: Adult; Hormone Replacement Therapy; Human Growth Hormone; Humans
PubMed: 23539718
DOI: 10.1210/jc.2012-4012 -
Endocrine Feb 2015In this review, the importance of growth hormone (GH) for the maintenance of normal cardiac function in adult life is discussed. Physiological effects of GH and... (Review)
Review
In this review, the importance of growth hormone (GH) for the maintenance of normal cardiac function in adult life is discussed. Physiological effects of GH and underlying mechanisms for interactions between GH and insulin-like growth factor I (IGF-I) and the cardiovascular system are covered as well as the cardiac dysfunction caused both by GH excess (acromegaly) and by GH deficiency in adult hypopituitary patients. In both acromegaly and adult GH deficiency, there is also increased cardiovascular morbidity and mortality possibly linked to aberrations in GH status. Finally, the status of the GH/IGF-I system in relation to heart failure and the potential of GH as a therapeutic tool in the treatment of heart failure are reviewed in this article.
Topics: Cardiovascular Physiological Phenomena; Heart; Heart Diseases; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Recombinant Proteins
PubMed: 24972804
DOI: 10.1007/s12020-014-0327-6 -
Genomics Jan 2020Personalized medicine, one of the main promises of the Human Genome Project (HGP) that began three decades ago, is now a new therapeutic paradigm. With its arrival the... (Review)
Review
Personalized medicine, one of the main promises of the Human Genome Project (HGP) that began three decades ago, is now a new therapeutic paradigm. With its arrival the era of developing drugs to suit all patients, yet often having to withdraw a promising new one because a minority of patients was at risk, even though it had proved valuable for the majority was consigned to history as were trial-and-error strategies being the predominant means of tailoring therapy. But how did it originate and the earliest examples emerge? Is it true that the first personalized diagnostic test was the companion test for Herceptin®? This account of a remarkable journey from genomic and translational research to therapeutic and diagnostic innovations, describes how sequencing the human growth hormone (hGH) locus provided proof of principle for HGP-inspired personalized medicine. Sequencing this locus and the resultant biomanufacture of HGH and the development of a test capable of detecting which patients would benefit from its administration helped silence the skeptics who questioned the validity of such an approach. The associated companion diagnostic was created four years before the invention of the HercepTest® (registered as the first companion diagnostics ever developed). By cultivating genomic research with passion and pursuing its applications, we and many others contributed to the emergence of a new diagnostics industry, the discovery of better actionable gene-targets and to a revitalized pharmaceutical industry capable of developing safer and more effective therapies. In combination, these developments are beginning to fulfill the promise of the HGP, offering each patient the opportunity to adopt the right treatment at the correct dosage in an opportune manner.
Topics: Genetic Loci; Genomics; Human Growth Hormone; Humans; Precision Medicine; Proof of Concept Study
PubMed: 31078717
DOI: 10.1016/j.ygeno.2019.05.006 -
Journal of Pediatric Endocrinology &... Jan 2018
Topics: Drug-Related Side Effects and Adverse Reactions; Growth Charts; Growth Disorders; Growth and Development; Human Growth Hormone; Humans; Reference Standards; Treatment Outcome; World Health Organization
PubMed: 29329107
DOI: 10.1515/jpem-2017-0531 -
Experimental Gerontology Aug 2015Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a... (Review)
Review
Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan.
Topics: Adolescent; Adult; Aging; Animals; Brain; Child; Growth Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Mice; Models, Biological; Neuronal Plasticity; Rats; Receptors, N-Methyl-D-Aspartate; Signal Transduction
PubMed: 25300732
DOI: 10.1016/j.exger.2014.10.002 -
Hormone Research 2007Children and adolescents treated for chronic diseases have non-specific metabolic abnormalities that lead to decreased growth velocity and abnormal body composition,... (Review)
Review
Children and adolescents treated for chronic diseases have non-specific metabolic abnormalities that lead to decreased growth velocity and abnormal body composition, including severe osteoporosis, muscle wasting and increased fat mass. Glucocorticoid (GC) therapy plays a major role in the complex pathogenesis of these metabolic abnormalities. Recombinant human growth hormone (rhGH) therapy was introduced a few years ago to reduce the severe disease- and GC-related metabolic consequences of juvenile idiopathic arthritis, other chronic diseases, and renal transplantation. Short- and mid-term rhGH treatment has consistently proved effective in overcoming GC-induced growth suppression, with a marked interindividual variability in the growth response to rhGH treatment. Safety of rhGH treatment, concerning the progression of the disease and glucose tolerance, was good. Prolonged follow-up until achievement of adult height is needed to better evaluate the impact of rhGH treatment on growth and body composition and the long-term consequences of hyperinsulinism.
Topics: Adolescent; Adrenal Cortex Hormones; Child; Growth Disorders; Human Growth Hormone; Humans; Metabolic Diseases; Recombinant Proteins
PubMed: 17356290
DOI: 10.1159/000100873 -
Neurologia Medico-chirurgica 2014The clinical syndrome of adult growth hormone deficiency (AGHD) was widely recognized in the 1980s. In this review, we first describe the clinical features and diagnosis... (Review)
Review
The clinical syndrome of adult growth hormone deficiency (AGHD) was widely recognized in the 1980s. In this review, we first describe the clinical features and diagnosis of AGHD and then state the effects of growth hormone (GH) therapy for these patients. The main characteristics of AGHD are abnormal body composition, dyslipidemia, insulin resistance, and an impaired quality of life (QoL) due to decreased psychological well-being. For diagnosing AGHD, the international consensus guidelines have suggested that an insulin tolerance test (ITT) is the gold standard, but in Japan, the growth hormone releasing peptide-2 (GHRP-2) test is available and is recommended as a convenient and safe GH stimulating test. The cut-off for diagnosing severe AGHD is a peak GH concentration of 9 g/L during the GHRP-2 test. Since 2006, GH therapy has been approved for Japanese patients with severe AGHD. For adults, GH replacement therapy should be initiated at a low dose (3 g/kg body weight/day), followed by individualized dose titration while monitoring patients' clinical status and serum insulin-like growth factor-I (IGF-I) concentrations. A variety of favorable effects of GH replacement have been indicated; however, it has not yet been established fully whether there is a direct effect of GH treatment on reducing mortality.
Topics: Adult; Age Factors; Body Composition; Diagnosis, Differential; Dyslipidemias; Human Growth Hormone; Humans; Insulin Resistance; Oligopeptides; Quality of Life
PubMed: 25070016
DOI: 10.2176/nmc.ra.2014-0088