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Best Practice & Research. Clinical... Feb 2017Growth hormone (GH) replacement therapy in adults with GH deficiency is still a challenge for the clinical endocrinologist and its implementation has still numerous... (Review)
Review
Growth hormone (GH) replacement therapy in adults with GH deficiency is still a challenge for the clinical endocrinologist and its implementation has still numerous difficulties and uncertainties. The decision to treat GH deficient adults requires a thoughtful and individualized evaluation of risks and benefits. Benefits have been found in body composition, bone health, cardiovascular risk factors, and quality of life. However, evidences for a reduction in cardiovascular events and mortality are still lacking, and treatment costs remain high. It is advisable to start treatment with low doses of GH, the goals being an appropriate clinical response, an avoidance of side effects, and IGF-I levels in the age-adjusted reference range. Although treatment appears to be overall safe, certain areas continue to require long-term surveillance, such as risks of glucose intolerance, pituitary/hypothalamic tumor recurrence, and cancer.
Topics: Adult; Body Composition; Bone and Bones; Cardiovascular Diseases; Glucose Intolerance; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hypopituitarism; Insulin-Like Growth Factor I; Male; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Reference Values; Risk Factors
PubMed: 28477728
DOI: 10.1016/j.beem.2017.03.001 -
International Journal of Molecular... Jun 2023Acromegaly is a rare disease with several systemic complications that may lead to increased overall morbidity and mortality. Despite several available treatments,... (Review)
Review
Acromegaly is a rare disease with several systemic complications that may lead to increased overall morbidity and mortality. Despite several available treatments, ranging from transsphenoidal resection of GH-producing adenomas to different medical therapies, complete hormonal control is not achieved in some cases. Some decades ago, estrogens were first used to treat acromegaly, resulting in a significant decrease in IGF1 levels. However, due to the consequent side effects of the high dose utilized, this treatment was later abandoned. The evidence that estrogens are able to blunt GH activity also derives from the evidence that women with GH deficiency taking oral estro-progestins pills need higher doses of GH replacement therapy. In recent years, the role of estrogens and Selective Estrogens Receptor Modulators (SERMs) in acromegaly treatment has been re-evaluated, especially considering poor control of the disease under first- and second-line medical treatment. In this review, we analyze the state of the art concerning the impact of estrogen and SERMs on the GH/IGF1 axis, focusing on molecular pathways and the possible implications for acromegaly treatment.
Topics: Humans; Female; Acromegaly; Selective Estrogen Receptor Modulators; Receptors, Estrogen; Estrogens; Adenoma; Insulin-Like Growth Factor I; Human Growth Hormone
PubMed: 37373068
DOI: 10.3390/ijms24129920 -
Hormone Research in Paediatrics 2022People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in... (Review)
Review
BACKGROUND
People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval.
SUMMARY
It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones.
KEY MESSAGES
The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.
Topics: Animals; Humans; Acromegaly; Dwarfism; Endocrine System Diseases; Growth Hormone; Human Growth Hormone; Pituitary Hormones, Anterior
PubMed: 36446319
DOI: 10.1159/000526440 -
International Journal of Molecular... May 2023Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review... (Review)
Review
Obesity is a growing public health problem worldwide, and GH and IGF-1 have been studied as potential therapeutic targets for managing this condition. This review article aims to provide a comprehensive view of the interplay between GH and IGF-1 and metabolism within the context of obesity. We conducted a systematic review of the literature that was published from 1993 to 2023, using MEDLINE, Embase, and Cochrane databases. We included studies that investigated the effects of GH and IGF-1 on adipose tissue metabolism, energy balance, and weight regulation in humans and animals. Our review highlights the physiological functions of GH and IGF-1 in adipose tissue metabolism, including lipolysis and adipogenesis. We also discuss the potential mechanisms underlying the effects of these hormones on energy balance, such as their influence on insulin sensitivity and appetite regulation. Additionally, we summarize the current evidence regarding the efficacy and safety of GH and IGF-1 as therapeutic targets for managing obesity, including in pharmacological interventions and hormone replacement therapy. Finally, we address the challenges and limitations of targeting GH and IGF-1 in obesity management.
Topics: Animals; Humans; Insulin-Like Growth Factor I; Growth Hormone; Obesity; Adipose Tissue; Insulin; Human Growth Hormone
PubMed: 37298507
DOI: 10.3390/ijms24119556 -
Archives of Endocrinology and Metabolism Aug 2019
Topics: Acromegaly; Brazil; Human Growth Hormone; Humans; Insulin-Like Growth Factor I
PubMed: 31460621
DOI: 10.20945/2359-3997000000163 -
Drug Design, Development and Therapy 2024Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily... (Review)
Review
Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy.
Topics: Adult; Humans; Child; United States; Human Growth Hormone; Dwarfism, Pituitary; Growth Hormone; Treatment Outcome; Insulin-Like Growth Factor I; Histidine; Mannitol; Phenol
PubMed: 38333899
DOI: 10.2147/DDDT.S315172 -
Frontiers in Endocrinology 2023Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity...
BACKGROUND
Growth hormone (GH) affects metabolism and regulates growth in childhood. The most prominent feature of GH deficiency (GHD) in children is diminished height velocity that eventually leads to short stature. In adult-onset GHD, lean body mass (LBM) is reduced, and visceral fat mass (FM) increased. Beneficial effects of GH treatment on body composition in adults with GHD, including an increase in muscle mass and a decrease in FM, are well established. Relatively few studies have investigated the effects of GH treatment on the body composition of pediatric patients with idiopathic or hypothalamic-pituitary disease-associated GH deficiency. This systematic review aimed to summarize available evidence relating to the effects of GH treatment on body composition in children with GHD.
METHODS
The PubMed, Science Direct, Cochrane Trials, and Embase databases, were searched with keywords including "GH", "body composition", "children", and "growth hormone" for English-language articles, published between January 1999 and March 2021. Two reviewers independently evaluated the search results and identified studies for inclusion based on the following criteria: participants had a confirmed diagnosis of GHD (as defined in each study); participants were pediatric patients who were receiving GH or had stopped GH treatment, regardless of whether they were pre- or post-pubertal; the intervention was recombinant human GH (rhGH; somatropin); and outcomes included changes in body composition during or after stopping GH therapy. Data extracted from each study included study quality, study sample characteristics, study interventions, and body composition. Data on fat-free mass and LBM were combined into a single category of LBM.
RESULTS
Sixteen studies reporting changes in body composition (i.e., FM and LBM) associated with GH treatment in children with GHD were identified and included in the review. Collectively, these studies demonstrated that FM decreased, and LBM increased in response to GH replacement therapy.
CONCLUSION
Despite study limitations (i.e., potential effects of diet and physical activity were not considered), we concluded that a periodic body composition assessment is required to ensure that a satisfactory body composition is achieved during GH replacement therapy in children with GHD.
Topics: Child; Humans; Body Composition; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism
PubMed: 36843617
DOI: 10.3389/fendo.2023.1093691 -
Molecular and Cellular Endocrinology Dec 2020Growth hormone (GH) and its mediator, insulin-like growth factor-1 (IGF-1), have long been recognized as central to human growth physiology. IGF-1 is known to complex... (Review)
Review
Growth hormone (GH) and its mediator, insulin-like growth factor-1 (IGF-1), have long been recognized as central to human growth physiology. IGF-1 is known to complex with IGF binding proteins as well as with the acid labile subunit (ALS) in order to prolong its half-life in circulation. Factors regulating the bioavailability of IGF-1 (i.e. the balance between free and bound IGF-1) were less well understood. Recently, pregnancy-associated plasma protein-A2 (PAPP-A2) was discovered as a protease which specifically cleaves IGF-binding protein (IGFBP)-3 and -5. PAPP-A2 deficient patients present with characteristic findings including growth failure, elevated total IGF-1 and -2, IGFBPs, and ALS, but decreased percentage of free to total IGF-1. Additionally, patients with PAPP-A2 deficiency have impairments in glucose metabolism and bone mineral density (BMD). Treatment with recombinant human IGF-1 (rhIGF-1) improved height SD scores, growth velocity, body composition, and dysglycemia. Mouse models recapitulate many of the human findings of PAPP-A2 deficiency. This review summarizes the function of PAPP-A2 and its contribution to the GH-IGF axis through an examination of PAPP-A2 deficient patients and mouse models, thereby emphasizing the importance of the regulation of IGF-1 bioavailability in human growth.
Topics: Animals; Female; Genetic Diseases, Inborn; Growth and Development; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Mice; Mutation; Pregnancy-Associated Plasma Protein-A; Signal Transduction
PubMed: 32739295
DOI: 10.1016/j.mce.2020.110967 -
Hepatology Communications Sep 2022Growth hormone and its mediator insulin-like growth factor-1 exert their effect on different organs and control various physiologic metabolic processes. Adult growth... (Review)
Review
Growth hormone and its mediator insulin-like growth factor-1 exert their effect on different organs and control various physiologic metabolic processes. Adult growth hormone deficiency (AGHD) presents with one or more components of metabolic syndrome and can be associated with nonalcoholic fatty liver disease (NAFLD). AGHD is present in spectrum of hypothalamic/pituitary disorders as well as cranial radiation of brain tumors and often remains underdiagnosed or untreated due to its nonspecific symptoms, relatively difficult diagnosis in some clinical scenarios, and various barriers to treatment. NAFLD usually develops soon after diagnosis of AGHD and might progress rapidly to nonalcoholic steatohepatitis (NASH) with advanced fibrosis, eventually requiring liver transplantation. A timely initiation of growth hormone replacement therapy might be important, although studies so far have demonstrated controversial results on NAFLD, primarily due to small sample size and different diagnostic methods of NAFLD. Increased awareness of the association between AGHD and NAFLD would facilitate early diagnosis of NAFLD and NASH if present. Therefore, a multidisciplinary approach involving hepatology and endocrinology should become a standard of care for these patients.
Topics: Adult; Hormone Replacement Therapy; Human Growth Hormone; Humans; Liver Transplantation; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
PubMed: 35765700
DOI: 10.1002/hep4.1953 -
The Journal of Clinical Endocrinology... Jun 2022Patients with obesity have a high prevalence of nonalcoholic fatty liver disease (NAFLD), representing a spectrum of simple steatosis to nonalcoholic steatohepatitis... (Review)
Review
Patients with obesity have a high prevalence of nonalcoholic fatty liver disease (NAFLD), representing a spectrum of simple steatosis to nonalcoholic steatohepatitis (NASH), without and with fibrosis. Understanding the etiology of NAFLD is clinically relevant since NAFLD is an independent risk factor for diabetes and cardiovascular disease. In addition, NASH predisposes patients to the development of cirrhosis and hepatocellular carcinoma, and NASH cirrhosis represents the fastest growing indication for liver transplantation in the United States. It is appreciated that multiple factors are involved in the development and progression of NAFLD. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) regulate metabolic, immune, and hepatic stellate cell function, and alterations in the production and function of GH is associated with obesity and NAFLD/NASH. Therefore, this review will focus on the potential role of GH and IGF1 in the regulation of hepatic steatosis, inflammation, and fibrosis.
Topics: Fibrosis; Growth Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Liver; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Obesity
PubMed: 35172328
DOI: 10.1210/clinem/dgac088