Injection Of Growth Hormone Research Articles

The effect of growth hormone on motor findings and dendrite morphology in an experimental Parkinson's disease model.

Approaches for the induction of neurogenesis and neuronal recovery through several modalities are gaining popularity in Parkinson's disease (PD). Growth hormone (GH) seems to have a role in the reversal of neural function following brain injury as well as in normal brain development and function; therefore, the use of GH may represent a feasible strategy in the management of PD. This experimental study aimed to evaluate the effect of growth hormone on motor function and dendrite morphology in rats with 6-hydroxydopamine (6-OHDA)-induced PD model. Thirty-six Sprague Dawley rats were included and randomly allocated into one of the six study groups: two controls and four treatment groups that received daily subcutaneous growth hormone injections for 21days, 1, 2, and 3months. PD model was induced through unilateral 6-OHDA injection to the nigrostriatal pathway. The following assessments were made: apomorphine rotation test, stepping test, and tissue examinations for tyrosine hydroxylase and dendrite morphology. The apomorphine rotation test and the stepping test confirmed the presence of PD. These tests as well as dendritic spine density/number and length assessments showed improvement in PD findings over time with GH administration. Findings of this study suggest that GH administration may improve dendrite morphology and motor function in the PD model, which may translate into symptom relief and quality of life improvement in patients with PD. Such potential benefits should be tested in robust clinical studies.

Development and validation of a novel treatment adherence, satisfaction and knowledge questionnaire (TASK-Q) for adult patients with hypothalamic-pituitary disorders

PurposeSuccessful treatment outcomes of adults with hypothalamic-pituitary disorders necessitate the adoption of intricate self-management behaviors, yet current scales for evaluating treatment adherence and satisfaction are inadequate for this patient group. This research introduces a novel treatment adherence, satisfaction and knowledge questionnaire (TASK-Q) developed specifically to identify patients’ unmet needs in better assessing and managing these disorders.MethodsThe study was conducted in three phases: (1) generating items and testing content validity, (2) refining these items through a pilot study, and (3) a main study evaluating the psychometric properties of the TASK-Q scale among 262 adults in a Pituitary Nurse-led Clinic, with 152 (58%) patients completing the questionnaire.ResultsExploratory factor analysis was used to test the factor structure and construct validity of the TASK-Q, revealing a 22-item scale divided into Satisfaction and Knowledge (17 items) and Adherence (5 items) subscales, and exhibiting high internal consistency (Cronbach’s α = 0.90). Significant correlations were identified between satisfaction and knowledge (r = 0.67, p < 0.001), satisfaction and adherence (r = 0.23, p = 0.005), and knowledge and adherence (r = 0.43, p < 0.001). Complex treatment regimens, like daily growth hormone injections and adjusting glucocorticoids during illness, negatively affected adherence (p < 0.001).ConclusionThe TASK-Q is a novel validated scale that can effectively evaluate patients’ perspectives on adherence, knowledge and satisfaction. Our findings highlight the significant impact of Advanced Nurse Practitioners in improving patient self-management behaviors, which likely leads to better treatment outcomes for people with hypothalamic-pituitary disorders.

I LAGH (ormoni della crescita long-acting): cosa sono e a chi proporli?

Children with growth hormone deficiency are currently treated with daily injections of recombinant growth hormone. The burden due to 365 injections per year and cold chain storage causes a poor medication adherence. Long-acting GH was developed to decrease injection frequency and to therefore promote a better therapeutic compliance. In this paper, we discuss about which long-acting drugs are currently on the market, their mechanism of action and which groups of patients may benefit from them.

Growth hormone treatment for neurologic symptoms of post-acute sequelae of COVID-19.

Following SARS-CoV-2 infection, some patients develop lingering neurologic symptoms of post-acute sequelae of COVID-19 (PASC) that commonly include fatigue and "brain fog." PASC symptoms are also linked with reduced growth hormone (GH) secretion, but GH treatment has not been tested to relieve symptoms. We enrolled 13 adults with neurologic PASC symptoms and peak stimulated GH secretion less than 10 ng/mL (glucagon stimulation) in a pilot study to receive 9 months of daily GH injections and an additional 3 months of off-treatment assessment. We compared peak stimulated GH secretion at baseline and 12 months and assessed measures of cognition, metabolism, body composition, and physical performance over the first 6 months of treatment. Patient-reported outcomes of fatigue, quality of life, sleep, and mood were recorded at baseline and compared with timepoints at 6, 9, and 12 months. GH treatment was associated with significantly improved scores for Brief Fatigue Inventory, Multidimensional Fatigue Symptom Inventory, Quality of Life Assessment of GrowthHormone Deficiency in Adults, Profile of Mood States, and Beck Depression Inventory-II, with no significant change in Pittsburgh Sleep Quality Index. Six months of adjunct GH treatment was not associated with significant changes in cognition, body composition, resting energy expenditure, or physical performance. Peak stimulated GH secretion was not altered at 12 months following 9 months of GH treatment. GH treatment significantly improved neurologic symptoms in PASC patients but cognition, sleep, and physical performance were not significantly altered.

Once-Weekly Somapacitan as an Alternative Management of Growth Hormone Deficiency in Prepubertal Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

Growth hormone treatment has effectively restored normal growth in children with growth hormone deficiency (GHD); however, it poses challenges in compliance with a daily growth hormone injection regimen, leading to low adherence and persistence rates. Once-weekly Somapacitan is a potential alternative for treating children with GHD. This study aimed to evaluate the efficacy, safety, and adherence of once-weekly subcutaneous Somapacitan compared to daily growth hormone injection in prepubertal children with GHD. A search for the published records was carried out on 17 October 2023 utilizing the searching feature available on PubMed, Embase, and Scopus. Primary study outcomes included (1) efficacy, measured by height velocity (HV), standard deviation score (SDs), height SDs, insulin-like growth factor-SDs (IGF-I SDs), and bone age vs. chronological age ratio (BA vs. CA); (2) safety, assessed through adverse events and injection site reactions; and (3) adherence, determined by the percentage of the sample completing treatments. Secondary outcomes evaluated disease burden scores, divided into three subgroup domains: emotional well-being, physical functional, and social well-being scores. We retrieved 6 studies that were eligible for the systematic review (417 versus 186 for intervention and control, respectively). Only 2 of the total included studies were eligible for pooled analysis (175 versus 82 for intervention and control, respectively). The efficacy profile of Somapacitan was similar to daily growth hormones, indicated by HV (mean difference (MD = 0.04; p = 0.96), HV SDs (MD = -0.71; p = 0.09), height SDs (MD = 0.11; p = 0.69), IGF-I SDs (MD = 0.06; p = 0.70), and CA vs. BA (MD = 0.67; p = 0.70)), demonstrated similar and non-inferior outcomes. Treatment adherence is 3 times higher in the Somapacitan group as compared to control (OR = 3.02; p = 0.03) with adherence rates reaching 95% and 88% for Somapacitan and Norditropin®, respectively. The disease burden measurement is similar in Somapacitan and daily growth hormones (MD = -0.62; p = 0.83), as indicated by the Growth Hormone Deficiency-Child Impact Measure. In almost all outcomes, the level of confidence is strong. The confidence level in the data is generally strong, but for CA vs. BA and the subgroup of severe adverse events with heterogeneity >50%, the confidence level is moderate. Although the efficacy and safety profiles of Somapacitan were found to be similar to those of daily growth hormones, a reduced frequency of once-weekly Somapacitan injections led to increased adherence. PROSPERO registration: CRD42023473209.

Nedostatak hormona rasta kod odraslih - dijagnoza i lečenje

Growth hormone deficiency (GHD) in adults is a rare clinical syndrome with an incidence of 1.4-4.2 per 100,000 persons per year and a prevalence of 350/million. It is characterized by unfavorable body composition, reduced muscle, and bone mass, lower capacity to endure physical effort, abnormal lipid profile, increased cardiovascular risk and poor quality of life. Despite these clinical manifestations, GHD is often unrecognized, so its diagnosis is often missed or delayed. The reason is the non-specific and subtle clinical characteristics, which require the testing of growth hormone (GH) secretion with stimulation tests. Two tests are in use, the insulin tolerance test and the glucagon test, which require the experience of the team performing them. Recently, an oral secretagogue of growth hormone - macimorelin has been used, which is simple test to perform and is safe for the patient. Insufficient secretion of GH in adults can be manifested as isolated or in combination with deficits of other pituitary hormones. However, GH is the most frequently detected hormonal deficit in adults as part of hypopituitarism. Causes of GHD can be congenital or acquired. Congenital reasons are the result of disorders of the embryogenic development of the pituitary gland and hypothalamus, and acquired are the most common complications of tumors of the sellar region and head trauma. Patients with GHD have an increased mortality rate compared to the general population. The causes of the shortened life span of these patients depend on the etiology of hypopituitarism, the applied therapy of tumors of the hypothalamus/pituitary region (surgery, radiotherapy), and the replacement of other missing pituitary hormones. During the last two decades, growth hormone therapy in adults has entered routine clinical practice. The beneficial effects of this substitution are reflected in the body composition, skeletal system, metabolic status, and improvement of the quality of life. GH replacement in adults returns the mortality rate to that expected for age in the general population. Due to the known proliferative, angiogenic, and anti-apoptotic properties of GH, there is still some caution regarding the recurrence of hypopituitarism-causing tumors or the appearance of new tumors during GH replacement. However, large and long-term follow-up studies of adults on GH therapy have shown a high safety profile of this treatment. Daily injections of GH were until recently the only way of its application, and now longacting weekly forms have been marketed, which will significantly improve adherence to this therapy.

Health-related quality of life in pre-pubertal children with pediatric growth hormone deficiency: 12-month results from a phase 3 clinical trial of once-weekly somatrogon versus once-daily somatropin

Objective Treatment of pediatric growth hormone deficiency (pGHD) with daily injection of recombinant human growth hormone (somatropin) aims to increase height velocity and improve health-related quality of life (HRQoL). The Quality of Life in Short Stature Youth (QoLISSY) questionnaire was administered in a phase 3 clinical trial that evaluated efficacy and safety of once-weekly somatrogon versus once-daily somatropin in children with pGHD (ClinicalTrials.gov no NCT02968004). Methods Treatment-naïve prepubertal children with pGHD received once-weekly somatrogon or once-daily somatropin for 12 months. The QoLISSY core module (physical/social/emotional subscales) was administered at baseline and 12 months after treatment initiation. QoLISSY-Parent was completed by parents/caregivers of children <7 years old and some parents/caregivers of children ≥7 years old; children ≥7 years old self-completed QoLISSY-Child. Results Baseline characteristics were similar between treatment groups (N = 117). Among children <7 years old, QoLISSY-Parent total and subscale scores showed similarly improved HRQoL at 12 months relative to baseline in both treatment groups. Self-reported QoLISSY-Child total and subscale scores in children ≥7 years old indicated HRQoL improvements at 12 months that were numerically better with somatrogon than somatropin (similar results with QoLISSY-Parent in this age group). At both time points, children reported better HRQoL than perceived by their parents/caregivers. Conclusion Treatment for 12 months with once-weekly somatrogon or once-daily somatropin resulted in comparable improvements in HRQoL among children with pGHD. Lower HRQoL perceived by parents/caregivers possibly reflect children’s tendency to emphasize adaptation. These results suggest that evaluation of HRQoL could help support treatment decisions in children with pGHD treated with growth hormone.

Growth Axis Somatostatin, Growth Hormone Receptor, and Insulin-like Growth Factor-1 Genes Express and Are Affected by the Injection of Exogenous Growth Hormone in Chinemys reevesii.

In this study, to explore the effect of growth hormone changes on the related genes and regulatory roles of the turtle, PCR amplification, real-time fluorescence quantitative analysis, and enzyme cutting technology were used to clone and sequence the somatostatin (SS) gene, growth hormone receptor (GHR), and insulin-like growth factor-1 (IGF-I) sequence of Chinemys reevesii. The effects of human growth hormone on the mRNA expression of growth-axis-related genes SS, GHR, and IGF-1 in different sexes were observed. The study of the SS gene in turtles using real-time fluorescence quantitative PCR showed that the SS gene was mainly expressed in the nervous system and the digestive system, with the highest expression found in the brain, while the GHR gene and the IGF-I gene were expressed in all tissues of Chinemys reevesii. The SS gene was expressed in the brain, pituitary, liver, stomach, and intestine, with the highest expression in the brain and the lowest expression in the liver. Within 4 weeks of the injection of exogenous growth hormone, the expression level of the SS gene in the brain of both sexes first increased and then decreased, showing a parabolic trend, and the expression level of the experimental group was lower than that of the control group. After the injection of growth hormone (GH), the expression of the GHR gene in the liver of both sexes showed a significant increase in the first week, decreasing to the control group level in the second week, and then gradually increasing. Finally, a significant level of difference in the expression of the GHR gene was reached at 3 and 4 weeks. In terms of the IGF-I gene, the changing trend of the expression level in the liver was the same as that of the GHR gene. After the injection of exogenous growth hormone, although the expression of the SS gene increased the inhibition of the secretion of the GHR gene by the Reeves' turtle, exogenous growth hormone could replace the synthesis of GH and GHR, accelerating the growth of the turtle. The experiments showed that the injection of recombinant human growth hormone affects the expression of SS, GHR, and IGF-1 genes, and promotes the growth of the Reeves' turtle.

THU049 Growth Hormone Treatment Reverses Deficits In POU1F1 Gene Mutation

Abstract Disclosure: S. Al-Samerria: None. J. Phelan: None. H. Xu: None. A. Negron: None. F. Wondisford: None. S. Radovick: None. Mutations in the Pit 1 gene, also known as POU1F1, have been linked to the deficient development of somatotrophs and the synthesis of growth hormone (GH) in the anterior pituitary gland. In a previous study, we reported a point mutation in the PIT1 gene caused by a substitution of a lysine (K) with a glutamic acid (E) at position 216 (K216E) on one allele in a patient presenting with combined pituitary hormone deficiency (CPHD). This patient had undetectable levels of GH, TSH, very low PRL, and severe mental retardation associated with short stature (SS). To study the effects of GH treatment on growth and metabolism in CPHD, we created a unique mouse model with the K216E mutation in the PIT1 gene using the CRISPR/Cas9 genome editing system. In this study, 4-week-old male and female homozygous mice were randomly divided into two groups. The treatment group received subcutaneous injections of GH (5 mg/g/day) for 5 consecutive days per week for 4 weeks, while the control group received saline injections on the same schedule. GH treatment significantly improved the growth and body composition of male and female mice bearing the K216E. GH treatment also increased metabolism as measured by oxygen consumption, carbon dioxide production, and energy expenditure. These effects were observed both during treatment and 4 weeks post-treatment, although some reversal of the changes in body composition was observed 4 weeks post-treatment. Our findings demonstrate the utility of this mouse model in studying the effects of GH deficiency and treatment on growth and metabolism. This model holds great promise in advancing our understanding of the underlying mechanisms of hypopituitarism and CPHD, potentially serving as a valuable tool in identifying metabolic biomarkers for these conditions. Presentation: Thursday, June 15, 2023

The Growth Hormone Deficiency (GHD) Reversal Trial: effect on final height of discontinuation versus continuation of growth hormone treatment in pubertal children with isolated GHD—a non-inferiority Randomised Controlled Trial (RCT)

Background Growth hormone deficiency (GHD) is the commonest endocrine cause of short stature and may occur in isolation (I-GHD) or combined with other pituitary hormone deficiencies. Around 500 children are diagnosed with GHD every year in the UK, of whom 75% have I-GHD. Growth hormone (GH) therapy improves growth in children with GHD, with the goal of achieving a normal final height (FH). GH therapy is given as daily injections until adult FH is reached. However, in many children with I-GHD their condition reverses, with a normal peak GH detected in 64–82% when re-tested at FH. Therefore, at some point between diagnosis and FH, I-GHD must have reversed, possibly due to increase in sex hormones during puberty. Despite increasing evidence for frequent I-GHD reversal, daily GH injections are traditionally continued until FH is achieved.Methods/designEvidence suggests that I-GHD children who re-test normal in early puberty reach a FH comparable to that of children without GHD. The GHD Reversal study will include 138 children from routine endocrine clinics in twelve UK and five Austrian centres with I-GHD (original peak GH < 6.7 mcg/L) whose deficiency has reversed on early re-testing. Children will be randomised to either continue or discontinue GH therapy. This phase III, international, multicentre, open-label, randomised controlled, non-inferiority trial (including an internal pilot study) will assess whether children with early I-GHD reversal who stop GH therapy achieve non-inferior near FH SDS (primary outcome; inferiority margin 0.55 SD), target height (TH) minus near FH, HRQoL, bone health index and lipid profiles (secondary outcomes) than those continuing GH. In addition, the study will assess cost-effectiveness of GH discontinuation in the early retesting scenario.DiscussionIf this study shows that a significant proportion of children with presumed I-GHD reversal generate enough GH naturally in puberty to achieve a near FH within the target range, then this new care pathway would rapidly improve national/international practice. An assumed 50% reversal rate would provide potential UK health service cost savings of £1.8–4.6 million (€2.05–5.24 million)/year in drug costs alone. This new care pathway would also prevent children from having unnecessary daily GH injections and consequent exposure to potential adverse effects.Trial registrationEudraCT number: 2020-001006-39

Growth Hormone Injection Log Analysis with Electronic Injection Device for Qualifying Adherence to Low-Irritant Formulation and Exploring Influential Factors on Adherence.

Although the treatment success of long-term growth hormone therapy (GHT) is dependent on maintaining patients' adherence to treatment, marked variations in adherence levels among children with GHT (eg, 7-71% nonadherence) have been reported. Barriers to or promoters of GHT adherence have been discussed and investigated, and digital health technologies, such as electronic GH injection devices, may have the potential to assess adherence to GHT more accurately. Thus, we conducted a multicenter, retrospective cohort study using GH injection log analysis of an electronic GH device, GROWJECTOR®L, to qualify adherence and explore the factors influencing adherence. This study enrolled 41 patients (median[range] age, 5.8[3.0 ~ 17.0] years) with short stature from nine Japanese medical institutions. The injection log data (12-48 weeks) were read by smartphones and collected into the data center through a cloud server. Although cumulative adherence rates remained higher than 95% throughout the observation period, five (12.2%) patients had low adherence (<85%). Subsequently, subgroup and logistic regression analyses for exploring factors affecting adherence revealed that self-selection of GH device and irregular injection schedule (ie, frequent injections after midnight) significantly affected adherence rate (p=0.034 and 0.048, respectively). In addition, higher rates of irregular injections significantly affected low adherence (median[range], 11.26[0.79 ~ 30.50]% vs 0.26[0.00 ~ 33.33]%, p = 0.029). Our study indicated that injection log analysis using an electronic GH device could detect irregular injection schedules due to a night owl or disturbance in lifetime rhythm affecting low adherence and had significant potential to encourage collaborative monitoring of adherence with healthcare providers and patients themselves/caregivers, along with growing autonomy and shared decision-making. Our study suggests the significance of narrative and personal approaches to adherence of patients with GHT and the usefulness of digital devices for such an approach and for removing various barriers to patient autonomy, leading to improvement and maintenance of adherence.

O-206 Growth hormone supplementation reduces aneuploidy and improves the quality of aged oocytes by activating the JAK2-ERK1/2 pathway

Abstract Study question Does growth hormone (GH) supplementation improves the quality of oocytes in aged mice via reducing aneuploidy? Summary answer Daily injections of GH for 8 weeks reduces aneuploidy by activating JAK2-ERK1/2 pathway and improves the quality of oocyte in aged mice. What is known already Aging-induced low-quality oocytes, which are mainly caused by aneuploidy, decrease female fertility. However, few treatments are available to improve the poor quality of oocytes in aged women. Age-related decline in GH levels may be related to the insufficient reproductive potential in aged women. Several studies have reported that GH improves assisted reproductive technology outcomes in poor ovarian response patients, although its role is still controversial. In animal models, GH supplementation improved the oocyte quality by enhancing mitochondrial function. However, whether GH reduces the aneuploidy rate in aged oocytes, and if so the underlying mechanisms, are unclear. Study design, size, duration The aged (8-month-old) C57BL/6J female mice were used in the study. For the in vivo experiments, the aged mice were intraperitoneally injected with GH (GenSci, Changchun, China; 1.6 mg/kg body weight) or an equivalent volume of normal saline for 8 weeks; For the in vitro experiments, germinal vesicle (GV) oocytes from aged mice were treated with GH (200 ng/mL) or PBS in M16 medium. Participants/materials, setting, methods We counted oocytes by immunohistochemistry to assess ovarian reserve. The expression of growth hormone receptor and mitochondrial genes were measured by quantitative real-time PCR. Time–lapse incubator was utilized to record the developmental potential of early embryos. Immunofluorescence was performed to assess parameters of oocyte quality (mitochondrial functions, spindle/chromosome defects, and DNA damage). Chromosome spread and DNA sequencing were used to analyze aneuploidy rate. We performed quantitative proteomics analysis to identify the potential targets of GH. Main results and the role of chance Firstly, we found that GH promoted GHR expression in aged oocytes (30.64±1.70 vs 21.68±1.08, P &amp;lt; 0.001). GH ameliorated aging-induced decline in ovarian reserve of aged mice, with increased ovarian index (0.040%±0.0031 vs 0.023%±0.0019, P &amp;lt; 0.01), and number of antral follicles (8.67±1.2 vs 3.33±0.88, P &amp;lt; 0.05) compared to the controls. In addition, GH improved the quality of aged oocytes, representing restored mitochondrial functions (P &amp;lt; 0.05), decreased DNA damage (23.37±1.76 vs 38.35±2.52, P &amp;lt; 0.001) . As expected, GH promoted the fertilization rate (39.9%±1.10 vs 14.4%±0.62, P &amp;lt; 0.001) and early embryo development (P &amp;lt; 0.01) of aged oocytes. Of note, GH recovered the spindle/chromosome defects (42.6%±2.12 vs 63.9%±1.83, P &amp;lt; 0.01, and reduced aneuploidy rate (20.9%±1.61 vs 39.3%±1.84, P &amp;lt; 0.01) in aged oocytes. GH activated ERK1/2 expression to decrease aneuploidy rate in aged oocytes. In addition, JAK2 might be involved in the regulation of GH on ERK1/2 expression in aged oocytes. Altogether, GH restored age-related decline in oocyte number, and decreased the occurrence rate of aneuploidy by activating JAK2-ERK1/2 pathway, thereby improving the quality of aged oocytes. Limitations, reasons for caution The molecular action mechanism of GH to regulate aneuploidy remains to be determined. Besides, future work should be extended to human oocyte to determine whether this mechanism is conserved between mice and humans Wider implications of the findings Our work expounds a theoretical basis for application of GH to improve the fertility of aged women. Besides, the results also feed new ideas for the prevention and treatment of oocyte quality decline in assisted reproductive technology. Trial registration number not applicable

Cost-effectiveness and cost-utility analysis of somatrogon once-weekly injections vs. daily growth hormone injection for treating paediatric growth hormone deficiency in Ireland

ObjectivesPaediatric growth hormone deficiency (pGHD) manifests as growth failure associated with inadequate growth hormone (GH) production. Daily injections of recombinant human GH (dGH) [somatropin] is the current standard of care, which has been shown to be well tolerated and effective, but associated with suboptimal adherence, leading to reduced effectiveness. Somatrogon, a once-weekly injectable long-acting human GH, has demonstrated clinical non-inferiority and significantly lower life interference (i.e. treatment burden) vs. somatropin in two Phase 3 studies. This work evaluated cost-effectiveness and cost-utility of somatrogon vs dGHs from an Irish payer perspective.MethodsA Markov model was developed for patients starting somatrogon or dGHs treatment at 3–12 years and continuing up to achievement of near adult height (NAH), with growth driven by trial-based height velocity (HV) and treatment-specific adherence. Patients could discontinue treatment at the end of Year 1 (4%). DGH adherence (95.3%–65% over treatment duration) and adherence-growth relationship were based on published evidence. Higher Year 1 adherence of 4%, tapering over time, for somatrogon vs. dGHs was based on clinical consultation. Treatment costs, monitoring costs and costs due to different wastage types (device setting and adherence) were sourced from local data. Health utilities based on height and injection frequency were derived from published literature. Scenario analysis, deterministic and probabilistic sensitivity analysis were performed.ResultsSomatrogon treatment led to 1.87–3.66 cm greater NAH gain and 0.21–0.50 higher quality adjusted life years (QALYs) vs. dGHs, across the base case and scenarios evaluated. Somatrogon treatment was associated with cost savings of €5,699–€21,974 and lower cost per cm gained vs. dGHs (€197–€527), per patient. Somatrogon was cost-effective vs. dGHs, with the result consistent across the sensitivity analyses conducted.ConclusionSomatrogon weekly injections were estimated to result in higher NAH, higher QALYs, lower overall costs and lower costs per cm gained than dGHs, in pGHD.

Mycobacterium Vaccae Vaccine Improve Incomplete Immune Recovery in AIDS Patients

Background: Mycobacterium seedling is rich in co-antigens and, a good immunomodulator with bidirectional immunomodulatory function. Objectives: The present study aimed to explore whether the Mycobacterium vaccae vaccine can improve the incomplete immune recovery of acquired immunodeficiency syndrome (AIDS) patients. Methods: According to the number of patients receiving human immunodeficiency virus (HIV) long-term treatment in the Ninth People’s Hospital of Chongqing, China, 100 patients with HIV-RNA quantitation of less than 103 cepies/ml, CD4 + T cell count less than 500/UL, and CD4+T cell count of more than 50/UL after 3 years of Haart treatment were selected. In total, they were randomly assigned to one of three groups, one group received an intramuscular injection of M. vaccae vaccine, one group received an intramuscular injection of growth hormone, and the last group received only a placebo injection. The levels and changes of naive T cells, Treg cells, total CD4+ T cells, T helper 1 (Th1), T helper 2 (Th2) cells, and interleukin 7 (IL-7) cytokine were measured at baseline and after 12, 48, and 50 weeks. Results: After 48 weeks of treatment, the total CD4+T cells, Th1 cells, and naive T cells in AIDS patients increased, while IL-7 cytokines, Treg cells, and Th2 cells decreased in M. vaccae vaccine and growth hormone group. There was no change in the placebo group, indicating that M. vaccae vaccine and growth hormone can improve the immune function of AIDS patients. After treatment, in group A (M. vaccae vaccine), there was an increase in the total CD4+T cells, Th1 cells, and naive T cells as well as a decrease in Treg cells, Th2 cells, and IL-7 cytokines. The only significant difference between M. vaccae vaccine and growth hormone groups was a decrease in Th1 cells in the M. vaccae vaccine group. After a 12-week follow-up, it was found that there were no cases of secondary infection in the M. vaccae vaccine group, one case in the growth hormone group, and five cases in the placebo group, demonstrating that the secondary infection rate in M. vaccae vaccine and the growth hormone groups was lower than that in the control group. Conclusion: The M. vaccae vaccine may decrease the levels of IL-7 as well as Treg and Th2 cells by increasing the levels of CD4+T cells, Th1 cells, and pure T cells in AIDS patients, leading to the improvement of immune reconstitution of AIDS patients to some extent.

Ghrelin regulates hyperactivity-like behaviors via growth hormone signaling pathway in zebrafish (Danio rerio).

Ghrelin is originally identified as the endogenous ligand for the growth hormone secretagogue receptor (GHSR) and partially acts by stimulating growth hormone (GH) release. Our previous studies have identified GHRELIN as a novel susceptibility gene for human attention-deficit hyperactivity disorder (ADHD), and ghrelin-depleted zebrafish (Danio rerio) display ADHD-like behaviors. However, the underlying molecular mechanism how ghrelin regulates hyperactivity-like behaviors is not yet known. Here, we performed RNA-sequencing analysis using adult ghrelin Δ/Δ zebrafish brains to investigate the underlying molecular mechanisms. We found that gh1 mRNA and genes related to the gh signaling pathway were significantly reduced at transcriptional expression levels. Quantitative polymerase chain reaction (qPCR) was performed and confirmed the downregulation of gh signaling pathway-related genes in ghrelin Δ/Δ zebrafish larvae and the brain of adult ghrelin Δ/Δ zebrafish. In addition, ghrelin Δ/Δ zebrafish displayed hyperactive and hyperreactive phenotypes, such as an increase in motor activity in swimming test and a hyperreactive phenotype under light/dark cycle stimulation, mimicking human ADHD symptoms. Intraperitoneal injection of recombinant human growth hormone (rhGH) partially rescued the hyperactivity and hyperreactive-like behaviors in ghrelin mutant zebrafish. Our results indicated that ghrelin may regulate hyperactivity-like behaviors by mediating gh signaling pathway in zebrafish. And the protective effect of rhGH on ghrelin Δ/Δ zebrafish hyperactivity behavior provides new therapeutic clues for ADHD patients.

Treatment burden, adherence, and quality of life in children with daily GH treatment in France.

The objective of this study was to describe in a real-life setting the treatment burden and adherence and quality of life (QOL) of children treated with daily injections of growth hormone and their relationship with treatment duration. This non-interventional, multicenter, cross-sectional French study involved children aged 3-17 years treated with daily growth hormone injections. Based on a recent validated dyad questionnaire, the mean overall life interference total score (100 = most interference) was described, with treatment adherence and QOL, using the Quality of Life of Short Stature Youth questionnaire (100 = best). All analyses were performed according to treatment duration prior to inclusion. Among the 275/277 analyzed children, 166 (60.4%) had only growth hormone deficiency (GHD). In the GHD group, the mean age was 11.7 ± 3.2 years; median treatment duration was 3.3 years (interquartile range 1.8-6.4). The mean overall life interference total score was 27.7 ± 20.7 (95% CI (24.2; 31.2)), with non-significant correlation with treatment duration (P = 0.1925). Treatment adherence was good (95.0% of children reported receiving >80% of planned injections over the last month); it slightly decreased with treatment duration (P = 0.0364). Children's overall QOL was good (81.5 ± 16.6 and 77.6 ± 18.7 according to children and parents, respectively), but subscores of the coping and treatment impact domains were <50. Similar results were observed in all patients independently of the condition requiring treatment. This real-life French cohort confirms the treatment burden of daily growth hormone injections, as previously reported in an interventional study.

Effectiveness of growth hormone in promoting endometrial growth in patients with endometrial dysplasia in frozen embryo transfer.

This study was designed to investigate the effect of growth hormone (GH) in promoting endometrial thickness, blood flow, and pregnancy outcome in patients with thin endometrium for frozen embryo transfer. Thirty-eight patients were recruited in the reproductive center of Jingzhou Hospital affiliated to Yangtze University who cancelled fresh embryo transfer due to thin endometrium and planned to undergo frozen-thawed embryo transfer (FET) from May 2019 to May 2020. The patients were randomly divided into the GH injection group (19 cases, endometrium preparation with hormone replacement therapy (HRT) and GH by subcutaneous injection) and the control group (19 cases, endometrium preparation with HRT). Both groups were similar in socio-demographic characteristics. After treatment, the thickness and volume of endometrium in the HRT & GH group were significantly increased (p < 0.05), and the growth rate was significantly higher than that in the control group (p < 0.05). The proportion of type A & B endometrium increased from 78.9% to 94.7% in the HRT & GH group. Moreover, the proportion of type Ⅰ and Ⅱ of endometrial blood perfusion in the HRT & GH group significantly increased compared with that before treatment. The human chorionic gonadotropin (hCG) positive rate (47.4 vs. 42.1%) and clinical pregnancy rate (36.8% vs. 31.6%) were slightly higher in the HRT&GH group than that in the control group. In conclusion, for patients with thin endometrium, HRT combined with subcutaneous injection of GH can increase the thickness and volume of the endometrium, improving the blood perfusion of the endometrium. This may play a positive role in improving endometrial receptivity and pregnancy outcome.

Somatotropin Penetration Testing from Formulations Applied Topically to the Skin

Growth hormone (somatotropin—STH) deficiency therapy requires daily injections of recombinant human growth hormone. The FDA approved treatment with STH with one dose per week for the first time in 2021. However, injectable drug application is accompanied by numerous inconveniences. Therefore, an attempt was made to formulate a less invasive STH formulation for topical application to the skin. A substrate was prepared based on a polymer, methylcellulose (MC), into which STH was introduced at a concentration of 1 mg/g. Simultaneously, formulations were made with STH, to which albumin (ALB) was added at different concentrations: 0.1%, 0.2% and 0.5%. A test of the degree of STH permeation was carried out, as well as the effect of ALB on STH permeation parameters. Selected rheological properties of the formulations obtained were investigated. A test of STH permeation in simulated in vivo conditions through porcine skin indicated a relatively good bioavailability of over 80% and confirmed the effectiveness of MC as a carrier for growth hormone. ALB prolonged the STH penetration rate and increased the penetration degree of STH to 93%. The hydrogels obtained were found to be typical shear-thinning, thixotropic fluids.

Growth hormone stimulates lipolysis in mice but not in adipose tissue or adipocyte culture.

The inhibitory effect of growth hormone (GH) on adipose tissue growth and the stimulatory effect of GH on lipolysis are well known, but the mechanisms underlying these effects are not completely understood. In this study, we revisited the effects of GH on adipose tissue growth and lipolysis in the lit/lit mouse model. The lit/lit mice are GH deficient because of a mutation in the GH releasing hormone receptor gene. We found that the lit/lit mice had more subcutaneous fat and larger adipocytes than their heterozygous lit/+ littermates and that these differences were partially reversed by 4-week GH injection. We also found that GH injection to the lit/lit mice caused the mature adipose tissue and adipocytes to reduce in size. These results demonstrate that GH inhibits adipose tissue growth at least in part by stimulating lipolysis. To determine the mechanism by which GH stimulates lipolysis, we cultured adipose tissue explants and adipocytes derived from lit/lit mice with GH and/or isoproterenol, an agonist of the beta-adrenergic receptors. These experiments showed that whereas isoproterenol, expectedly, stimulated potent lipolysis, GH, surprisingly, had no effect on basal lipolysis or isoproterenol-induced lipolysis in adipose tissue explants or adipocytes. We also found that both isoproterenol-induced lipolysis and phosphorylation of hormone-sensitive lipase were not different between lit/lit and lit/+ mice. Taken together, these results support the conclusion that GH has lipolytic effect in mice but argue against the notion that GH stimulates lipolysis by directly acting on adipocytes or by enhancing β-adrenergic receptors-mediated lipolysis.

Guidance for the treatment of adult growth hormone deficiency with somapacitan, a long-acting growth hormone preparation.

Adult growth hormone deficiency (AGHD) is a rare endocrine disorder characterized by an abnormal body composition, metabolic abnormalities associated with increased cardiovascular diseases, bone loss, and impaired quality of life. Daily subcutaneous injections with recombinant growth hormone (GH) can alleviate the abnormalities associated with AGHD. Several long-acting GH (LAGH) preparations are currently in development that aim to reduce treatment burden for patients receiving daily GH injections. Somapacitan (Sogroya®; Novo Nordisk, Denmark) is the first LAGH preparation that has been approved for treatment of AGHD in the United States, Europe, and Japan. The recent approval of somapacitan and anticipated approval of other LAGH molecules presents new questions for physicians planning to treat AGHD with LAGH in the future. Differences in the technologies used to prolong the half-life of recombinant GH are expected to result in variations in pharmacokinetic and pharmacodynamic profiles between preparations. Therefore, it is essential that physicians understand and consider such variations when treating patients with these novel GH replacement therapies. Here, we present a set of treatment recommendations that have been created to guide physicians initiating therapy with somapacitan in patients with AGHD who are eligible for GH replacement. Furthermore, we will review the published data that underlie these recommendations to explain the rationale for the treatment and monitoring advice provided.