Evaluation of layer-by-layer assembly systems for drug delivery and antimicrobial properties in orthopaedic application.

Layer-by-layer self-assembly systems were developed using monolayer and multilayer carriers to prevent infections and improve bone regeneration of porous Ti-6Al-4V scaffolds. These polymeric carriers incorporated (Gel/Alg-IGF-1 + Chi-Cef) and (4Gel/Alg-IGF-1 + Chi-Cef) on the surface of porous implants produced via electron beam melting (EBM). The results showed that the drug release from multilayer carriers was higher than that of monolayers after 14 days. However, the carrier containing Gel/Alg-IGF-1 + Chi-Cef exhibited more sustained behavior. Cell morphology was characterized, revealing that multilayer carriers had higher cell adhesion than monolayers. Additionally, cell differentiation was significantly greater for (Gel/Alg-IGF-1) + Chi-Cef, and (4Gel/Alg-IGF-1) + Chi-Cef multilayer carriers than for the monolayer groups after 7 days. Notably, the drug dosage was effective and did not interfere, and the cell viability assay showed safe results. Antibacterial evaluations demonstrated that both multilayer carriers had a greater effect on Staphylococcus aureus during treatment. The carriers containing lower alginate had notably less effect than the other studied carriers. This study aimed to test systems for controlling drug release, which will be applied to improve MG63 cell behavior and prevent bacterial accumulation during orthopaedic applications.

IGF-1 rs6218 polymorphisms modulate the susceptibility to age-related cataract.

Background: Single nucleotide polymorphisms (SNPs), as the most abundant form of DNA variation in the human genome, contribute to age-related cataracts (ARC) development. Apoptosis of lens epithelial cells (LECs) is closely related to ARC formation. Insulin-like growth factor 1 (IGF1) contributes to cell apoptosis regulation. Moreover, IGF1 was indicated to exhibit a close association with cataract formation. Afterward, an investigation was conducted to examine the correlation between polymorphisms in IGF1 and the susceptibility to ARC. Methods: The present investigation was a case-control study. Venous blood draws were collected from the participants for DNA genotyping. Lens capsule samples were collected to detect mRNA and apoptosis. TaqMan RT-PCR was used to detect IGF1 polymorphism genotypes and qRT PCR was used to detect IGF1 mRNA levels in LECs. LEC apoptosis was evaluated through flow cytometry. The chi-square test was used to compare differences between ARCs and controls of each SNP. Results: We found that the G allele frequency in the IGF1-rs6218 was higher in the ARCs than in the controls. Furthermore, it was observed that the rs6218 GG genotype exhibited a positive correlation to elevated levels of IGF1 mRNA in LECs. The IGF1 mRNA in the LECs and the apoptosis of LECs in nuclear type of ARCs (ARNC) was higher than the controls. Conclusion: The susceptibility to ARC was related to IGF1-rs6218 polymorphism, and this polymorphism is associated with IGF1 expression at the mRNA level. Moreover, apoptosis in LECs of ARNCs was found to be increased.

Intramuscular injection of mesenchymal stem cells augments basal muscle protein synthesis after bouts of resistance exercise in male mice.

Skeletal muscle mass is critical for activities of daily living. Resistance training maintains or increases muscle mass, and various strategies maximize the training adaptation. Mesenchymal stem cells (MSCs) are multipotent cells with differential potency in skeletal muscle cells and the capacity to secrete growth factors. However, little is known regarding the effect of intramuscular injection of MSCs on basal muscle protein synthesis and catabolic systems after resistance training. Here, we measured changes in basal muscle protein synthesis, the ubiquitin-proteasome system, and autophagy-lysosome system-related factors after bouts of resistance exercise by intramuscular injection of MSCs. Mice performed three bouts of resistance exercise (each consisting of 50 maximal isometric contractions elicited by electrical stimulation) on the right gastrocnemius muscle every 48 h, and immediately after the first bout, mice were intramuscularly injected with either MSCs (2.0 × 106 cells) labeled with green fluorescence protein (GFP) or vehicle only placebo. Seventy-two hours after the third exercise bout, GFP was detected only in the muscle injected with MSCs with concomitant elevation of muscle protein synthesis. The injection of MSCs also increased protein ubiquitination. These results suggest that the intramuscular injection of MSCs augmented muscle protein turnover at the basal state after consecutive resistance exercise.

Growth hormone resistance induced by amino acid deprivation in fao cells is independent of FGF21.

Adequate dietary intake of amino acids is imperative for normal animal growth. Our previous work using rat hepatocarcinoma Fao cells demonstrated that growth hormone (GH) resistance, coupled with a concurrent reduction in insulin-like growth factor 1 (Igf1) mRNA levels, may underlie the growth retardation associated with a low-protein diet (LPD). In this study, we investigated whether FGF21 contributes to liver GH resistance in Fao rat hepatoma cells under amino acid deprivation conditions. Mice subjected to an LPD exhibited growth retardation, compromised GH signaling in the liver, and decreased blood IGF-1 levels compared with those on a control diet. To assess the potential involvement of fibroblast growth factor (FGF) 21, produced in response to amino acid deficiency, in the development of GH resistance, we examined GH signaling and Igf1 mRNA levels in Fao cells cultured in amino acid-deprived medium. Despite the inhibition of Fgf21 expression by the integrated stress response inhibitor, an inhibitor of the eukaryotic initiation factor 2-activating transcription factor 4 pathway, GH resistance persisted in response to amino acid deprivation. Additionally, the introduction of FGF21 into the control medium did not impair either GH signaling or GH-induced Igf1 transcription. These data suggest that, in Fao cells, amino acid deprivation induces GH resistance independently of FGF21 activity. By shedding light on the mechanisms behind growth retardation-associated GH resistance linked to amino acid deficiencies, our findings provide valuable insights for clinicians in formulating effective treatment strategies for individuals facing these challenges.

Association of Insulin-like Growth Factor-1 with Bone Mineral Density in Survivors of Childhood Acute Leukemia.

In this study, we investigated bone mineral deficits in children who survived childhood acute leukemia and explored the association between the insulin-like growth factor-1 (IGF-1) level and bone mineral density (BMD). This retrospective analysis enrolled 214 patients treated for acute leukemia, measuring various factors including height, weight, body mass index (BMI), and lumbar spine BMD after the end of treatment. The study found an overall prevalence of low BMD in 15% of participants. Notably, IGF-1 levels were significantly different between patients with low BMD and those with normal BMD, and correlation analyses revealed associations of the IGF-1 level and BMI with lumbar spine BMD. Regression analyses further supported this relationship, suggesting that higher IGF-1 levels were associated with a decreased risk of low BMD. The study findings suggest that IGF-1 may serve as a valuable tool for evaluating and predicting osteoporosis in survivors of childhood acute leukemia.

IGF1R deficiency in vascular smooth muscle cells impairs myogenic autoregulation and cognition in mice.

Introduction: Cerebrovascular pathologies contribute to cognitive decline during aging, leading to vascular cognitive impairment and dementia (VCID). Levels of circulating insulin-like growth factor 1 (IGF-1), a vasoprotective hormone, decrease during aging. Decreased circulating IGF-1 in animal models leads to the development of VCID-like symptoms, but the cellular mechanisms underlying IGF-1-deficiency associated pathologies in the aged cerebrovasculature remain poorly understood. Here, we test the hypothesis that vascular smooth muscle cells (VSMCs) play an integral part in mediating the vasoprotective effects of IGF-1. Methods: We used a hypertension-based model of cerebrovascular dysfunction in mice with VSMC-specific IGF-1 receptor (Igf1r) deficiency and evaluated the development of cerebrovascular pathologies and cognitive dysfunction. Results: VSMC-specific Igf1r deficiency led to impaired cerebral myogenic autoregulation, independent of blood pressure changes, which was also associated with impaired spatial learning and memory function as measured by radial arm water maze and impaired motor learning measured by rotarod. In contrast, VSMC-specific IGF-1 receptor knockdown did not lead to cerebral microvascular rarefaction. Discussion: These studies suggest that VSMCs are key targets for IGF-1 in the context of cerebrovascular health, playing a role in vessel stability alongside other cells in the neurovascular unit, and that VSMC dysfunction in aging likely contributes to VCID.

Transplantation of Neural Stem Cells Loaded in an IGF-1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI.

Anabolic myokine responses and muscular performance following 8 weeks of autoregulated compared to linear resistance exercise in recreationally active males.

BACKGROUND: To date, no studies, to our knowledge, have compared the efficacy of autoregulated periodized and linear resistance exercises on anabolic myokines and muscular performance among recreationally active individuals. This study aimed to compare the effects of an 8-week autoregulated periodized resistance exercise (APRE) program with a linear resistance exercise (LRE) program on insulin-like growth factor-1 (IGF-1), follistatin (FST), myostatin (MST), body composition, muscular strength, and power in recreationally active males. METHODS: Thirty males were randomly assigned to either the APRE group (n = 15) or the LRE group (n = 15). Participants completed training three times a week for 8 weeks. The outcome measures included serum IGF-1, FST, MST, muscular strength (isometric knee extension and handgrip), power (vertical jump), lean body mass, and fat mass. RESULTS: IGF-1 circulating levels increased over time following APRE (34%) and with no significant change following LRE (~-1%). There were no significant differences over time or between groups for FST or MST. Muscular strength (knee extension [21.5 vs. ~16%] and handgrip [right: 31 vs. 25%; left: 31.7 vs. 28.8%]) and power (~ 33 vs. ~26%) significantly increased to a greater extent following APRE compared to LRE. Interestingly, the results revealed that lean body mass increased over time only after APRE (~ 3%), but not LRE. CONCLUSION: These findings suggest that APRE may be more effective than LRE in increasing muscular strength, power, and lean body mass, as well as circulating IGF-1 levels, in recreationally active males. The observed differences may be attributed to the increased training volume associated with APRE. However, further research is needed to directly assess muscle protein synthesis.

Surface modification of additive manufactured Ti6Al4V scaffolds with gelatin/alginate- IGF-1 carrier: An effective approach for healing bone defects.

The study investigates the potential of porous scaffolds with Gel/Alg-IGF-1 coatings as a viable candidate for orthopaedic implants. The scaffolds are composed of additively manufactured Ti6Al4V lattices, which were treated in an alkali solution to obtain the anatase and rutile phases. The treated surface exhibited hydrophilicity of <11.5°. A biopolymer carrier containing Insulin-like growth factor 1 was coated on the samples using immersion treatment. This study showed that the surface-modified porous Ti6Al4V scaffolds increased cell viability and proliferation, indicating potential for bone regeneration. The results demonstrate that surface modifications can enhance the osteoconduction and osteoinduction of Ti6Al4V implants, leading to improved bone regeneration and faster recovery. The porous Ti6Al4V scaffolds modified with surface coating of Gel/Alg-IGF-1 exhibited a noteworthy increase in cell viability (from 80.7 to 104.1%viability) and proliferation. These results suggest that the surface modified scaffolds have potential for use in treating bone defects.

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension.

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = -0.49), systolic blood pressure (SBP) (-0.44), and carotid intima-media thickness (cIMT) (-0.43). The IGF-1R expression was negatively correlated with PWV (r = -0.42) and SBP (r = -0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions.

Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.

Cancer remains a significant global health concern, with lung cancer consistently leading as one of the most common malignancies. Genetic aberrations involving receptor tyrosine kinases (RTKs) are known to be associated with cancer initiation and development, but RTK involvement in smoking-associated lung cancer cases is not well understood. The Insulin-like Growth Factor 1 Receptor (IGF-1R) is a receptor that plays a critical role in lung cancer development. Its signaling pathway affects the growth and survival of cancer cells, and high expression is linked to poor prognosis and resistance to treatment. Several reports have shown that by activating IGF-1R, tobacco smoke-related carcinogens promote lung cancer and chemotherapy resistance. However, the relationship between IGF-1R and cancer is complex and can vary depending on the type of cancer. Ongoing investigations are focused on developing therapeutic strategies to target IGF-1R and overcome chemotherapy resistance. Overall, this review explores the intricate connections between tobacco smoke-specific carcinogens and the IGF-1R pathway in lung carcinogenesis. This review further highlights the challenges in using IGF-1R inhibitors as targeted therapy for lung cancer due to structural similarities with insulin receptors. Overcoming these obstacles may require a comprehensive approach combining IGF-1R inhibition with other selective agents for successful cancer treatment.

Association of Insulin-like Growth Factor-1 and Neurofilament Light Chain in Patients with Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is the most common primary tauopathy. The definite diagnosis of PSP is established by histopathologic changes in the brain. There are no reliable blood-based biomarkers to aid the diagnosis of this fatal disease at an early stage. Also, the precise etiopathology of PSP and its variants is inadequately understood. Objective: Blood-based molecules such as neurofilament light chain (NfL) and insulin-like growth factor-1 (IGF-1) are shown as important markers of neurodegenerative and aging processes, respectively. These two biomarkers have not been analyzed simultaneously in PSP patients. Methods: To address this knowledge gap, 40 PSP patients and equal number of healthy individuals were recruited and serum levels of NfL and IGF-1 were assayed in all the study participants by enzyme-linked immunosorbent assay (ELISA). Motor and nonmotor symptoms were evaluated in PSP patients using various scales/questionnaires. Cardiac autonomic function tests were performed in a subset of patients (n = 27). Results: A significantly high serum level of NfL (P < 0.01) and a reduced level of IGF-1 (P = 0.02) were observed in PSP patients compared to healthy controls. Besides, a negative correlation (r = -0.54, P < 0.01) between NfL and IGF-1 levels was observed in PSP patients. Conclusion: The finding of this study reinforces the important role of blood NfL level as a potential biomarker of PSP. Further, the current study provides novel insights into the reciprocal correlation between NfL and IGF-1 in PSP patients. Combined analysis of blood levels of these two functionally relevant markers might be useful in the prediction and diagnosis of PSP.

Identification of IGF-1 Effects on White Adipose Tissue and Hippocampus in Alzheimer's Disease Mice via Transcriptomic and Cellular Analysis.

Alzheimer's disease (AD) stands as the most prevalent neurodegenerative disorder, characterized by a multitude of pathological manifestations, prominently marked by the aggregation of amyloid beta. Recent investigations have revealed a compelling association between excessive adiposity and glial activation, further correlating with cognitive impairments. Additionally, alterations in levels of insulin-like growth factor 1 (IGF-1) have been reported in individuals with metabolic conditions accompanied by memory dysfunction. Hence, our research endeavors to comprehensively explore the impact of IGF-1 on the hippocampus and adipose tissue in the context of Alzheimer's disease. To address this, we have conducted an in-depth analysis utilizing APP/PS2 transgenic mice, recognized as a well-established mouse model for Alzheimer's disease. Upon administering IGF-1 injections to the APP/PS2 mice, we observed notable alterations in their behavioral patterns, prompting us to undertake a comprehensive transcriptomic analysis of both the hippocampal and adipose tissues. Our data unveiled significant modifications in the functional profiles of these tissues. Specifically, in the hippocampus, we identified changes associated with synaptic activity and neuroinflammation. Concurrently, the adipose tissue displayed shifts in processes related to fat browning and cell death signaling. In addition to these findings, our analysis enabled the identification of a collection of long non-coding RNAs and circular RNAs that exhibited significant changes in expression subsequent to the administration of IGF-1 injections. Furthermore, we endeavored to predict the potential roles of these identified RNA molecules within the context of our study. In summary, our study offers valuable transcriptome data for hippocampal and adipose tissues within an Alzheimer's disease model and posits a significant role for IGF-1 within both the hippocampus and adipose tissue.

Efficacy of pasireotide LAR for acromegaly: a prolonged real-world monocentric study.

Background: Acromegaly is caused by excessive growth hormone (GH) and insulin-like growth factor 1 (IGF1). Medical therapy plays a role as a treatment option for persistent disease after non-curative surgery or as a first-line therapy when surgery is not feasible. Pasireotide-LAR (Pas-LAR) is recommended for patients with acromegaly as second-line treatment. Aim: To evaluate the patients characteristics predictive of an adequate response to Pas-LAR and the long-term efficacy and safety of the Pas-LAR treatment. Methods: Data from 19 patients with active acromegaly, who were and resistant or intolerant to first-line medical therapy and were switched to pas-LAR have been retrospectively collected. We compared the baseline clinical and biochemical characteristics of patients who were found to respond to Pas-LAR therapy (responders, n=14) with those of patients who did not respond (non-responders, n=5). We then evaluated the Pas-LAR efficacy and safety during long-term follow-up in responders. Results: IGF1 normalization occurred in 71.4% of responders after one injection. IGF1 levels, [median(interquartile range) of the upper limit of the normal range (ULN) fold increase] were higher in non-responders compared to responders within the initial month of therapy [1.40(1.30-2.34) vs 0.70(0.55-1.25), respectively, p=0.009] and after three [1.77(1.74-2.29) vs 0.94(0.82-1.13), respectively, p=0.029] and six months [1.68(1.33-1.72) vs 1.00(0.65 -1.28), respectively, p=0.002]. Out of 6 patients with symptomatic headache (all in responder group), 5 and 1 reported the resolution and improvement of headache, respectively, already after the first injection. Median HbA1c levels tended to increase from baseline to 6 months both in responder (36 mMol/Mol to 42 mMol/Mol) and non-responder patients (45 mMol/Mol to 48 mMol/Mol). During long term follow up, in the responder group 2 new patients developed diabetes. Tumor shrinkage was observed in 6 out of 7 evaluated responders, with no cases of size increase during the long-term follow-up. Conclusion: Pas-LAR is effective and safe and the early identification of responders is possible just after the first administration.

Traditional Pediatric Massage Enhanced Hippocampal GR, BDNF and IGF-1 Expressions and Exerted an Anti-depressant Effect in an Adolescent Rat Model of CUMS-induced Depression.

This study aimed to investigate the anti-depressant effect of traditional pediatric massage (TPM) in adolescent rats and its possible mechanism. The adolescent depression model in rats was established by using chronic unpredictable mild stress (CUMS). All rats were randomly divided into five groups (seven per group), including the groups of control (CON), CUMS, CUMS with TPM, CUMS with back stroking massage (BSM) and CUMS with fluoxetine (FLX). The tests of sucrose preference, Morris water maze and elevated plus maze were used to evaluate depression-related behaviors. Plasma corticosterone (CORT) level was measured by ELISA. The gene and protein expressions of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) were measured by RT-qPCR and IHC respectively. The results showed that CUMS induced depression-related behaviors in the adolescent rats, along with decreased weight gain and reduced hippocampal expressions of GR, IGF-1 and BDNF. TPM could effectively prevent depression-related behaviors in CUMS-exposed adolescent rats, manifested as increasing weight gain, sucrose consumption, ratio of open-arm entry, times of crossing the specific quadrant and shortening escape latency. TPM also decreased CORT level in plasma, together with enhancing expressions of GR, IGF-1 and BDNF in the hippocampus. These results may support the clinical application of TPM to prevent and treat adolescent depression.

Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects.

Cerebrovascular fragility and cerebral microhemorrhages (CMH) contribute to age-related cognitive impairment, mobility defects, and vascular cognitive impairment and dementia, impairing healthspan and reducing quality of life in the elderly. Insulin-like growth factor 1 (IGF-1) is a key vasoprotective growth factor that is reduced during aging. Circulating IGF-1 deficiency leads to the development of CMH and other signs of cerebrovascular dysfunction. Here our goal was to understand the contribution of IGF-1 signaling on vascular smooth muscle cells (VSMCs) to the development of CMH and associated gait defects. We used an inducible VSMC-specific promoter and an IGF-1 receptor (Igf1r) floxed mouse line (Myh11-CreERT2 Igf1rf/f) to knockdown Igf1r. Angiotensin II in combination with L-NAME-induced hypertension was used to elicit CMH. We observed that VSMC-specific Igf1r knockdown mice had accelerated development of CMH, and subsequent associated gait irregularities. These phenotypes were accompanied by upregulation of a cluster of pro-inflammatory genes associated with VSMC maladaptation. Collectively our findings support an essential role for VSMCs as a target for the vasoprotective effects of IGF-1, and suggest that VSMC dysfunction in aging may contribute to the development of CMH.

Climate change and its effects on body size and shape: the role of endocrine mechanisms.

In many organisms, rapidly changing environmental conditions are inducing dramatic shifts in diverse phenotypic traits with consequences for fitness and population viability. However, the mechanisms that underlie these responses remain poorly understood. Endocrine signalling systems often influence suites of traits and are sensitive to changes in environmental conditions; they are thus ideal candidates for uncovering both plastic and evolved consequences of climate change. Here, we use body size and shape, a set of integrated traits predicted to shift in response to rising temperatures with effects on fitness, and insulin-like growth factor-1 as a case study to explore these ideas. We review what is known about changes in body size and shape in response to rising temperatures and then illustrate why endocrine signalling systems are likely to be critical in mediating these effects. Lastly, we discuss research approaches that will advance understanding of the processes that underlie rapid responses to climate change and the role endocrine systems will have. Knowledge of the mechanisms involved in phenotypic responses to climate change will be essential for predicting both the ecological and the long-term evolutionary consequences of a warming climate. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Growth hormone-secreting pituitary adenoma combined with Graves' disease: retrospective case series and literature review.

Purpose: The coexistence of growth hormone-secreting pituitary adenoma (GHPA) and Graves' disease (GD) is rare. This study aimed to investigate the relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) levels and thyroid function in patients with GHPA combined with GD and to explore the underlying mechanisms. Methods: Eleven patients with GHPA combined with GD during 2015-2022 were collected by searching the medical record system of Beijing Tiantan Hospital, Capital Medical University. Changes in GH/IGF-1 levels and thyroid function were compared before and after the application of antithyroid drugs (ATD) and before and after transsphenoidal surgery (TSS) or somatostatin analog (SSA) treatment, respectively. Results: After the application of ATD, with the decrease of thyroid hormone levels, GH/IGF-1 levels also decreased gradually. In patients without ATD application, after surgery or SSA treatment, thyroid hormone levels decreased as GH/IGF-1 decreased. Conclusion: Hyperthyroidism due to GD promotes the secretion of GH/IGF-1, and when thyroid hormone levels were decreased by the use of ATD, GH and IGF-1 levels were also decreased, suggesting that thyroid hormones may influence the synthesis and secretion of GH/IGF-1. The use of ATD to control thyrotoxicosis before TSS is not only beneficial in reducing the risk of anesthesia but may help to promote biochemical control of GHPA. On the other hand, high levels of GH/IGF-1 in patients with GHPA also exacerbate GD hyperthyroidism, which is ameliorated by a decrease in GH/IGF-1 levels by TSS or SSA treatment, suggesting that the GH-IGF-1 axis promotes growth, thyroid function, and thyroid hormone metabolism.

Challenges of insulin-like growth factor-1 testing.

Insulin-like growth factor 1 (IGF-1), primarily synthesized in the liver, was initially discovered due to its capacity to replicate the metabolic effects of insulin. Subsequently, it emerged as a key regulator of the actions of growth hormone (GH), managing critical processes like cell proliferation, differentiation, and apoptosis. Notably, IGF-1 displays a longer half-life compared to GH, making it less susceptible to factors that may affect GH concentrations. Consequently, the measurement of IGF-1 proves to be more specific and sensitive when diagnosing conditions such as acromegaly or GH deficiency. The recognition of the existence of IGFBPs and their potential to interfere with IGF-1 immunoassays urged the implementation of various techniques to moderate this issue and provide accurate IGF-1 results. Additionally, in response to the limitations associated with IGF-1 immunoassays and the occurrence of discordant IGF-1 results, modern mass spectrometric methods were developed to facilitate the quantification of IGF-1 levels. Taking advantage of their ability to minimize the interference caused by IGF-1 variants, mass spectrometric methods offer the capacity to deliver robust, reliable, and accurate IGF-1 results, relying on the precision of mass measurements. This also enables the potential detection of pathogenic mutations through protein sequence analysis. However, despite the analytical challenges, the discordance in IGF-1 reference intervals can be attributed to a multitude of factors, potentially leading to distinct interpretations of results. The establishment of reference intervals for each assay is a demanding task, and it requires nationwide multicenter collaboration among laboratorians, clinicians, and assay manufacturers to achieve this common goal in a cost-effective and resource-efficient manner. In this comprehensive review, we examine the challenges associated with the standardization of IGF-1 measurement methods, the minimization of pre-analytical factors, and the harmonization of reference intervals. Particular emphasis will be placed on the development of IGF-1 measurement techniques using "top-down" or "bottom-up" mass spectrometric methods.

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.