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Growth Hormone & IGF Research :... Feb 2024Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children...
OBJECTIVE
Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition.
DESIGN
An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients.
RESULTS/CONCLUSIONS
Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.
Topics: Adult; Child; Humans; Brain; Brain Neoplasms; Cancer Survivors; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Patient Transfer
PubMed: 38368660
DOI: 10.1016/j.ghir.2024.101573 -
Clinical Endocrinology Apr 2024Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of somapacitan in Japanese children with GHD after 104 weeks of treatment and after switch from daily GH.
DESIGN
Subanalysis on Japanese patients from a randomised, open-labelled, controlled parallel-group phase 3 trial (REAL4, NCT03811535).
PATIENTS AND MEASUREMENTS
Thirty treatment-naïve patients were randomised 2:1 to somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day) up to Week 52, after which all patients received somapacitan. Height velocity (HV; cm/year) at Weeks 52 and 104 were the primary measurements. Additional assessments included HV SD score (SDS), height SDS, bone age, insulin-like growth factor-I (IGF-I) SDS, and observer-reported outcomes.
RESULTS
At Week 52, observed mean HV was similar between treatment groups (10.3 vs. 9.8 cm/year for somapacitan and daily GH, respectively). Similar HVs between groups were also observed at Week 104: 7.4 cm/year after continuous somapacitan treatment (soma/soma) and 7.9 cm/year after 1-year somapacitan treatment following switch from daily GH (switch). Other height-related endpoints supported continuous growth. IGF-I SDS increased in both groups with mean IGF-I SDS within -2 and +2 during the study. Somapacitan was well tolerated, one mild injection site reaction was reported, with no reports of injection site pain. Patient preference questionnaires showed that most patients and their caregivers (90.9%) who switched treatment at Week 52 preferred once-weekly somapacitan over daily GH treatment.
CONCLUSIONS
Somapacitan showed sustained efficacy in Japanese children with GHD over 104 weeks and for 52 weeks after switching from daily GH. Somapacitan was well tolerated and preferred over daily GH.
Topics: Child; Humans; Growth Hormone; Insulin-Like Growth Factor I; Japan; Human Growth Hormone; Dwarfism, Pituitary; Histidine; Mannitol; Phenol
PubMed: 38368603
DOI: 10.1111/cen.15025 -
Gene May 2024Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR)....
BACKGROUND
Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR). The aim of this study was to identify the molecular etiology of a Chinese boy with IGHD.
METHODS
Whole-exome sequencing, sanger sequencing and bioinformatic analysis were performed to screen for candidate mutations. The impacts of candidate mutation on gene expression, intracellular localization and protein function were further evaluated by in vitro assays.
RESULTS
A novel heterozygous frameshift mutation in the GHRH gene (c.91dupC, p.R31Pfs*98) was identified in a Chinese boy clinically diagnosed as having IGHD. The mutation was absent in multiple public databases, and considered as deleterious using in silico prediction, conservative analysis and three-dimensional homology modeling. Furthermore, mRNA and protein expression levels of mutant GHRH were significantly increased than wild-type GHRH (p < 0.05). Moreover, mutant GHRH showed an aberrant accumulation within the cytoplasm, and obviously reduced ability to stimulate GH secretion and cAMP accumulation in human GHRHR-expressing pituitary GH3 cells compared to wild-type GHRH (p < 0.05).
CONCLUSION
Our study discovered the first loss-of function mutation of GHRH in a Chinese boy with IGHD and provided new insights on IGHD pathogenesis caused by GHRH haploinsufficiency.
Topics: Humans; Male; China; Dwarfism, Pituitary; Frameshift Mutation; Growth Hormone; Human Growth Hormone; Mutation; Receptors, Neuropeptide; Receptors, Pituitary Hormone-Regulating Hormone; Growth Hormone-Releasing Hormone; East Asian People
PubMed: 38354915
DOI: 10.1016/j.gene.2024.148283 -
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) is crucial to growth and development. GH secretion is regulated by a complex feedback system involving the pituitary gland, hypothalamus, and other... (Review)
Review
Growth hormone (GH) is crucial to growth and development. GH secretion is regulated by a complex feedback system involving the pituitary gland, hypothalamus, and other organs, and predominantly occurs during deep sleep. Isolated and idiopathic growth hormone deficiency (GHD) is a condition characterized by GHD without any other signs or symptoms associated with a specific syndrome or disease. The aim of this narrative review was to evaluate the relationship between GH and sleep in children using published data. Various databases (Medline/PubMed, Scopus, and Web of Science) were systematically searched for relevant English language articles published up to April 2023. Search strategies included the terms 'children/pediatric', 'growth hormone', 'growth hormone deficiency' and 'sleep'. Data were extracted by two independent reviewers; 185 papers were identified of which 58 were duplicates and 118 were excluded (unrelated n=83, syndromic/genetic GHD n=17, non-English n=13, abstract n=1, case report n=1). Overall, nine studies (six clinical studies, two case series, and one survey) were included. GHD appears to have an adverse effect on sleep in children, and GH therapy has only been shown to have a beneficial effect on sleep parameters in some individuals. Notably, identified data were limited, old/poor quality, and heterogenous/inconsistent. Further research of GHD in pediatric populations is necessary to improve the understanding of GHD impact on sleep and its underlying mechanisms, and to determine the specific impacts of GH therapy on sleep in children.
Topics: Humans; Child; Growth Hormone; Human Growth Hormone; Hypopituitarism; Dwarfism, Pituitary; Sleep
PubMed: 38327902
DOI: 10.3389/fendo.2023.1332114 -
Indian Pediatrics Feb 2024To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS).
OBJECTIVE
To analyse the clinical and radiological characteristics of pituitary stalk interruption syndrome (PSIS).
METHODS
A retrospective analysis of confirmed cases of PSIS was performed. The development of new pituitary hormonal deficiencies and response to recombinant human growth hormone (rhGH) therapy were assessed during follow-up.
RESULTS
This study included 14 children (10 boys) of PSIS with median (range) age of 12.15 years (2 months - 18 years). Short stature was the most common presentation (n = 13), and micropenis (n = 4), cleft lip (n = 1) and single central incisor (n = 1) were other midline defects. Growth hormone (GH) deficiency was present in 14 children and 7 of them also had multiple pituitary hormone deficiencies at baseline. Central hypothyroidism (n = 5), secondary adrenal deficiency (n = 4) and gonadotropin deficiencies (n = 2) were also seen. All children received rhGH. The mean height gain on follow-up was 12.78 cm in first year (n = 14), 6.5 cm in second year (n = 8) and 4.07 cm in third year (n = 7) of rhGH therapy. Four children developed additional pituitary hormone deficiency on follow-up.
CONCLUSION
Short stature with isolated GH deficiency was the most common presentation of PSIS that showed good response to rhGH therapy.
Topics: Child; Humans; Male; Dwarfism, Pituitary; Growth Hormone; Human Growth Hormone; Hypopituitarism; Pituitary Gland; Retrospective Studies; Female; Infant; Child, Preschool; Adolescent
PubMed: 38321728
DOI: No ID Found -
Growth Hormone & IGF Research :... Feb 2024Growth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility...
PURPOSE
Growth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility after GH replacement. The frequency of GH deficiency is not established in patients diagnosed with unexplained infertility. Here, we aim to present the prevalence of GH deficieny in this patient group.
METHODS
We included patients diagnosed with unexplained infertility throughout 18 months. Insulin tolerance test (ITT) and glucagon stimulation tests (GST) were performed and insufficient response to both tests was required for the diagnosis of GH deficiency.
RESULTS
Twenty-five patients were included in the study, the mean age was 27.4 ± 4.5 years and the median duration of infertility was 60 months (min:14, max:120). Two patients were GH deficient according to GST and 14 to ITT. Two patients (8%) showed lack of response on both tests and were diagnosed with GH deficiency.
CONCLUSION
The rate of GH deficiency among women with unexplained infertility was 8% in this preliminary study. There is need for further studies with larger patient groups to verify the results.
Topics: Humans; Female; Young Adult; Adult; Hypopituitarism; Growth Hormone; Dwarfism, Pituitary; Human Growth Hormone; Infertility; Insulin
PubMed: 38280246
DOI: 10.1016/j.ghir.2024.101571 -
Journal of Clinical Research in... May 2024The aim of this study was to evaluate executive function (EF), such as inhibition and working memory, in children with isolated growth hormone deficiency (IGHD) using...
OBJECTIVE
The aim of this study was to evaluate executive function (EF), such as inhibition and working memory, in children with isolated growth hormone deficiency (IGHD) using performance-based tests and parent-report scales.
METHODS
A total of seventy children between the ages of 7 and 12 years were included in the study. Half (n=35) had children with IGHD and half were healthy controls. To evaluate the EF performances of the participants, the Visual Aural Digit Span Test-B Form (VADS-B) and Stroop task were applied. EF was also evaluated using the Behavior Rating Inventory of Executive Function (BRIEF).
RESULTS
Children with IGHD scored lower on the VADS-B form for short-term memory (p<0.05) compared to healthy controls. In addition, the completion time for the Stroop-color/word test was significantly longer in children with IGHD (p<0.05). For children with IGHD, their parents reported higher scores on all sub-scales of the BRIEF scale, with statistically significant differences for all sub-scales with the exception of “organization of materials” (p<0.05).
CONCLUSION
In this study, children with IGHD had poorer EF skills compared to unaffected peers. EF skills may influence academic success by affecting children’s language skills, mathematical comprehension, cognitive flexibility, and hypothetical thinking. We believe that psychiatric evaluation of children with IGHD before and during treatment may positively contribute to both their academic performance and social relationships.
Topics: Humans; Child; Female; Executive Function; Male; Cross-Sectional Studies; Human Growth Hormone; Neuropsychological Tests; Dwarfism, Pituitary; Memory, Short-Term; Case-Control Studies
PubMed: 38275147
DOI: 10.4274/jcrpe.galenos.2024.2023-10-6 -
Journal of Endocrinological... Jul 2024Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on...
PURPOSE
Growth hormone deficiency (GHD) is a rare condition with a worldwide prevalence of 1 patient in 4000 to 10,000 live births, placing a significant economic burden on healthcare systems. The aim of this study is to generate evidence on the economic burden of children and adolescents with GHD treated with rhGH and their parents in Italy.
METHODS
A cost of illness analysis, adopting the prevalence approach, has been developed, producing evidence on the total annual cost sustained by the Italian National Health System (NHS) and by the society. The study is based on original data collected from a survey conducted among Italian children and adolescents with GHD and their parents.
RESULTS
143 children/adolescents with GHD and their parents participated to the survey, conducted from May to October 2021. Patients had a mean age of 12.2 years (SD: 3.1) and were mostly males (68.5%). The average direct healthcare cost sustained by the NHS was € 8,497.2 per patient/year; adding the out-of-pocket expenses (co-payments and expenses for private healthcare service), the total expense was € 8,568.6. The indirect costs, assessed with the human capital approach, were € 847.9 per patient/year. The total of direct and indirect cost is € 9,345.1 from the NHS perspective, and € 9,416.5 from a social perspective. The total cost incurred by the Italian NHS for children with GHD (range: 5,708-8,354) was estimated in € 48.5-71.0 million, corresponding to 0.04-0.06% of the total Italian public health expense in the year 2020.
CONCLUSIONS
The total annual cost for GHD children is close to € 10,000, and is mainly due to the cost of rhGH treatment. This cost is almost entirely sustained by the NHS, with negligible out-of-pocket expenses. The economic burden on the Italian NHS for the health care of established GHD children is fourfold higher than the prevalence of the disease in the overall Italian population.
Topics: Humans; Male; Italy; Cost of Illness; Child; Female; Adolescent; Human Growth Hormone; Health Care Costs; Health Expenditures; Dwarfism, Pituitary; Growth Disorders; Prevalence; Parents
PubMed: 38198073
DOI: 10.1007/s40618-023-02277-z -
Zhongguo Dang Dai Er Ke Za Zhi =... Dec 2023The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in...
The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.
Topics: Child; Humans; Growth Hormone; Insulin-Like Growth Factor I; Insulin-Like Peptides; Insulin-Like Growth Factor Binding Protein 3; Human Growth Hormone; Dwarfism, Pituitary
PubMed: 38112135
DOI: 10.7499/j.issn.1008-8830.2308076