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American Journal of Medical Genetics.... Dec 2022The evaluation of endocrine involvement in RASopathies is important for the care and follow-up of patients affected by these conditions. Short stature is a cardinal... (Review)
Review
The evaluation of endocrine involvement in RASopathies is important for the care and follow-up of patients affected by these conditions. Short stature is a cardinal feature of RASopathies and correlates with multiple factors. Growth hormone treatment is a therapeutic possibility to improve height and quality of life. Assessment of growth rate and growth laboratory parameters is routine, but age at start of therapy, dose and effects of growth hormone on final height need to be clarified. Puberty disorders and gonadal dysfunction, in particular in males, are other endocrinological areas to evaluate for their effects on growth and development. Thyroid dysfunction, autoimmune disease and bone involvement have also been reported in RASopathies. In this brief review, we describe the current knowledge on growth, growth hormone therapy, endocrinological involvement in patients affected by RASopathies.
Topics: Male; Humans; Quality of Life; Growth Hormone; Human Growth Hormone; Puberty; Body Height
PubMed: 36401574
DOI: 10.1002/ajmg.c.32013 -
European Journal of Pediatrics Mar 2024As we continue to understand more about the complex mechanism of growth, a plethora of novel therapies have recently been developed that aim to address barriers and... (Review)
Review
As we continue to understand more about the complex mechanism of growth, a plethora of novel therapies have recently been developed that aim to address barriers and optimize efficacy. This review aims to explore these novel therapies and provide a succinct review based on the latest clinical studies in order to introduce clinicians to therapies that will soon constitute the future in the field of short stature. Conclusion: The review focuses on long-acting growth hormone formulations, a novel growth hormone oral secretagogue, novel treatments for children with achondroplasia, and targeted therapies for rare forms of skeletal dysplasias. What is Known: • Recombinant human growth hormone has been the mainstay of treatment for children with short stature for years. • Such therapy is not always effective based on the underlying diagnosis (e.g achondroplasia, Turner syndrome). Compliance with daily injections is challenging and can directly affect efficacy. What is New: • Recent development of long-acting growth hormone regimens and oral secretagogues can overcome some of these barriers, however several limitations need to be taken into consideration. • Newer therapies for achondroplasia, and other rare forms of skeletal dysplasias introduce us to a new era of targeted therapies for children with short stature. Clinicians ought to be aware of pitfalls and caveats before introducing these novel therapies to every day practice.
Topics: Child; Humans; Growth Disorders; Human Growth Hormone; Growth Hormone; Turner Syndrome; Achondroplasia
PubMed: 37831302
DOI: 10.1007/s00431-023-05239-y -
Endocrinology and Metabolism Clinics of... Jun 2023Growth hormone (GH) secretion declines with aging (somatopause). One of the most controversial issues in aging is GH treatment of older adults without evidence of... (Review)
Review
Growth hormone (GH) secretion declines with aging (somatopause). One of the most controversial issues in aging is GH treatment of older adults without evidence of pituitary pathology. Although some clinicians have proposed reversing the GH decline in the older population, most information comes from not placebo-controlled studies. Although most animal studies reported an association between decreased GH levels (or GH resistance) and increased lifespan, human models have shown contradictory reports on the consequences of GH deficiency (GHD) on longevity. Currently, GH treatment in adults is only indicated for individuals with childhood-onset GHD transitioning to adulthood or new-onset GHD due to hypothalamic or pituitary pathologic processes.
Topics: Aged; Humans; Aging; Growth Hormone; Human Growth Hormone; Hypopituitarism; Insulin-Like Growth Factor I; Pituitary Gland
PubMed: 36948778
DOI: 10.1016/j.ecl.2022.10.003 -
Frontiers in Endocrinology 2022In contemporary ART, the use of "add-ons" during ovarian stimulation has increased, especially in poor responders. Growth Hormone (GH) is an adjunctive therapy that has... (Review)
Review
In contemporary ART, the use of "add-ons" during ovarian stimulation has increased, especially in poor responders. Growth Hormone (GH) is an adjunctive therapy that has been studied extensively in the translational and clinical setting, with an ongoing scientific debate over its effectiveness and optimal use. In this review, we aim to provide an overview of the physiologic basis for the use of GH in ART, and to summarize the latest evidence regarding its clinical use, primarily as an adjunct to ovarian stimulation, but also in the IVF lab and with regards to its effects on the endometrium.
Topics: Female; Humans; Growth Hormone; Fertilization in Vitro; Ovulation Induction; Human Growth Hormone; Reproduction
PubMed: 36531455
DOI: 10.3389/fendo.2022.1055097 -
Paediatric Drugs Jan 2022Lonapegsomatropin (lonapegsomatropin-tcgd; SKYTROFA), a long-acting prodrug of somatropin (human growth hormone), is in development by Ascendis Pharma as a treatment for... (Review)
Review
Lonapegsomatropin (lonapegsomatropin-tcgd; SKYTROFA), a long-acting prodrug of somatropin (human growth hormone), is in development by Ascendis Pharma as a treatment for growth hormone deficiency in pediatric and adult patients. Lonapegsomatropin received its first approval in August 2021 in the USA for the treatment of pediatric patients at least 1 year of age (and weighing ≥ 11.5 kg) with growth failure due to inadequate secretion of endogenous growth hormone. Lonapegsomatropin is administered as a once-weekly subcutaneous injection; the sustained release of somatropin from lonapegsomatropin eliminates the need for daily somatropin injections. This article summarizes the milestones in the development of lonapegsomatropin leading to this first pediatric approval for the treatment of growth hormone deficiency.
Topics: Adult; Child; Growth Hormone; Human Growth Hormone; Humans; Injections, Subcutaneous
PubMed: 34709591
DOI: 10.1007/s40272-021-00478-8 -
Molecular and Cellular Endocrinology Dec 2020In this review, I summarize historical and recent features of the classical pathways activated by growth hormone (GH) through the cell surface GH receptor (GHR). GHR is... (Review)
Review
In this review, I summarize historical and recent features of the classical pathways activated by growth hormone (GH) through the cell surface GH receptor (GHR). GHR is a cytokine receptor superfamily member that signals by activating the non-receptor tyrosine kinase, JAK2, and members of the Src family kinases. Activation of the GHR engages STATs, PI3K, and ERK pathways, among others, and details of these now-classical pathways are presented. Modulating elements, including the SOCS proteins, phosphatases, and regulated GHR metalloproteolysis, are discussed. In addition, a novel physical and functional interaction of GHR with IGF-1R is summarized and discussed in terms of its mechanisms, consequences, and physiological and therapeutic implications.
Topics: Animals; Growth Hormone; Human Growth Hormone; Humans; Receptors, Somatotropin; Signal Transduction
PubMed: 32835785
DOI: 10.1016/j.mce.2020.110999 -
Journal of Endocrinological... Jun 2017In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and... (Review)
Review
BACKGROUND
In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term efficacy and safety.
AIM
We here reviewed the emerging aspects of the use of PEG in clinical practice in the light of the most recent literature.
RESULTS
The clinical use of PEG is still suboptimal, considering that it remains the most powerful tool to control IGF-I in acromegaly allowing to obtain, with a pharmacological treatment, the most important clinical effects in terms of signs and symptoms, quality of life and comorbidities. The number of patients with acromegaly exposed to PEG worldwide has become quite elevated and the prolonged follow-up allows now to deal quite satisfactorily with many clinical issues including major safety issues, such as the concerns about possible tumour (re)growth under PEG. The positive or neutral impact of PEG on glucose metabolism has been highlighted, and the clinical experience, although limited, with sleep apnoea and pregnancy has been reviewed. Finally, the current concept of somatostatin receptor ligands (SRL) resistance has been addressed, in order to better define the acromegaly patients to whom the PEG option may be offered.
CONCLUSIONS
PEG increasingly appears to be an effective and safe medical option for many patients not controlled by SRL but its use still needs to be optimized.
Topics: Acromegaly; Animals; Human Growth Hormone; Humans
PubMed: 28176221
DOI: 10.1007/s40618-017-0614-1 -
Neuroendocrinology 2016Historically, medical treatment of acromegaly has mainly been used as an adjuvant therapy after surgery. In the last decades, an increased range of medical therapy... (Review)
Review
Historically, medical treatment of acromegaly has mainly been used as an adjuvant therapy after surgery. In the last decades, an increased range of medical therapy options has been available. Somatostatin analogues have become the cornerstones of medical treatment in acromegaly and are even seen as a primary treatment in a selected group of acromegaly patients. The most recent medical treatment available for acromegaly patients is pegvisomant, a growth hormone receptor antagonist. To date, it is the most effective medical treatment, but it is costly. Pegvisomant is used as monotherapy and combined with somatostatin analogues. In this article, we review clinical studies and cohorts that have documented the efficacy of pegvisomant monotherapy and combined therapy and give a concise overview of associated side effects.
Topics: Acromegaly; Drug Therapy, Combination; Hormone Antagonists; Human Growth Hormone; Humans; Octreotide; Somatostatin
PubMed: 25792221
DOI: 10.1159/000381644 -
Growth Hormone & IGF Research :... 2023Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain... (Review)
Review
Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain permanently below the 3rd centile for height, though their short stature might result from a multifactorial etiology, not-yet fully understood. The secretion of growth hormone (GH) following the classic GH stimulation tests is often normal, with baseline insulin-like growth factor-1 (IGF-1) levels at the lower normal limits, but patients with Noonan syndrome have also a possible moderate response to GH therapy, leading to a final increased height and substantial improvement in growth rate. Aim of this review was to evaluate both safety and efficacy of GH therapy in children and adolescents with Noonan syndrome, also evaluating as a secondary aim the possible correlations between the underlying genetic mutations and GH responses.
Topics: Adolescent; Humans; Child; Growth Hormone; Noonan Syndrome; Human Growth Hormone; Insulin-Like Growth Factor I; Growth Disorders; Mutation; Body Height
PubMed: 37084633
DOI: 10.1016/j.ghir.2023.101532 -
Endocrine-related Cancer Sep 2023Despite landmark advances in cancer treatments over the last 20 years, cancer remains the second highest cause of death worldwide, much ascribed to intrinsic and... (Review)
Review
Despite landmark advances in cancer treatments over the last 20 years, cancer remains the second highest cause of death worldwide, much ascribed to intrinsic and acquired resistance to the available therapeutic options. In this review, we address this impending issue, by focusing the spotlight on the rapidly emerging role of growth hormone action mediated by two intimately related tumoral growth factors - growth hormone (GH) and insulin-like growth factor 1 (IGF1). Here, we not only catalog the scientific evidences relating specifically to cancer therapy resistance inflicted by GH and IGF1 but also discuss the pitfalls, merits, outstanding questions and the future need of exploiting GH-IGF1 inhibition to tackle cancer treatment successfully.
Topics: Humans; Human Growth Hormone; Insulin-Like Growth Factor I; Neoplasms; Growth Hormone
PubMed: 37283510
DOI: 10.1530/ERC-22-0414