Sophia Krombholz , Andreas Thomas , Philippe Delahaut , Martin Bidlingmaier , Katharina Schilbach , Geoffrey Miller , Mario Thevis
{"title":"A combined top-down and bottom-up LC-HRMS/MS method for the quantification of human growth hormone in plasma and serum","authors":"Sophia Krombholz , Andreas Thomas , Philippe Delahaut , Martin Bidlingmaier , Katharina Schilbach , Geoffrey Miller , Mario Thevis","doi":"10.1016/j.ghir.2023.101560","DOIUrl":"10.1016/j.ghir.2023.101560","url":null,"abstract":"<div><h3>Objective</h3><p>The precise and accurate quantification of human growth hormone (GH) in plasma/ serum is crucial for the diagnosis and treatment of diseases like GH deficiency or acromegaly. However, the ligand-binding assays (LBAs) currently used for routine testing show considerable methodological variability. Here, we present a complementary, combined top-down and bottom-up LC-MS-based method to quantify (intact) GH in plasma and serum, which concurrently provides a basis for a MS-based analysis of GH in doping controls.</p></div><div><h3>Design</h3><p>Extraction of GH from plasma/ serum was accomplished by protein precipitation, followed by an immunocapture step using protein A-coupled magnetic beads and a polyclonal anti-GH antibody. The intact protein was subsequently analyzed top-down on a 2D-LC-HRMS/MS system. In addition, sample extracts were digested with trypsin and analyzed for signal peptides corresponding to ‘total’, 22 kDa and 20 kDa GH (bottom-up). Both assays were validated according to current guidelines and compared to the GH isoform differential immunoassay used in routine doping control analysis. GH concentrations in serum samples of healthy adults, patients with acromegaly, and in samples obtained after administration of recombinant GH were analyzed as proof-of-principle.</p></div><div><h3>Results</h3><p>The intact monomeric 22 kDa isoform of GH was selectively quantified in a representative working range of 0.5 to 10 ng/ml by top-down LC-HRMS/MS. Subsequent bottom-up analysis provided additional data on ‘total’ and 20 kDa GH. Top-down and bottom-up assay results for the 22 kDa isoform correlated well with the corresponding immunoassay results (R<sup>2</sup> > 0.95). For a possible application of the method in an anti-doping context, the ratio between 22 kDa and ‘total’ GH was evaluated, indicating differences between the various donor groups, but only with limited significance.</p></div><div><h3>Conclusion</h3><p>The top-down and bottom-up LC-HRMS/MS method developed here presents a valuable tool for the quantification of GH in plasma/ serum complementary to established LBAs used at present in clinical measurements. Albeit the examination of the GH isoform proportions by the LC-MS method does not yet allow for the assessment of GH abuse, the obtained findings provide an important basis to enable LC-MS-based GH analysis of doping control samples in the future.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"72 ","pages":"Article 101560"},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles L. Cai , Matthew Marcelino , Jacob V. Aranda , Kay D. Beharry
{"title":"Comparison of hyperoxia or normoxia resolution of intermittent hypoxia and intermittent hyperoxia episodes on liver histopathology, IGF-1, IGFBP-3, and GHBP in neonatal rats","authors":"Charles L. Cai , Matthew Marcelino , Jacob V. Aranda , Kay D. Beharry","doi":"10.1016/j.ghir.2023.101559","DOIUrl":"10.1016/j.ghir.2023.101559","url":null,"abstract":"<div><h3>Objective</h3><p>Extremely low gestational age neonates requiring oxygen therapy for chronic lung disease<span><span> experience repeated fluctuations in arterial oxygen saturation, or </span>intermittent hypoxia<span><span> (IH), during the first few weeks of life. These events are associated with a high risk for reduced growth, hypertension, and insulin resistance in later life. This study tested the hypothesis that IH, or intermittent hyperoxia have similar negative effects on the liver; somatic growth; and liver insulin-like growth factor (IGF)-I, </span>IGF binding protein<span> (BP)-3, and growth hormone binding protein (GHBP), regardless of resolution in normoxia or hyperoxia between episodes.</span></span></span></p></div><div><h3>Design</h3><p><span>Newborn rats on the first day of life (P0) were exposed to two IH paradigms: 1) hyperoxia (50% O</span><sub>2</sub><span>) with brief hypoxia (12% O</span><sub>2</sub>); or 2) normoxia (21% O<sub>2</sub>) with hypoxia (12% O<sub>2</sub>); intermittent hypoxia (50% O<sub>2</sub>/21% O<sub>2</sub>); hyperoxia only (50% O<sub>2</sub>); or room air (RA, 21% O<sub>2</sub><span><span>). Pups were euthanized on P14 or placed in RA until P21. Controls remained in RA from P0-P21. Growth, liver </span>histopathology<span>, apoptosis, IGF</span></span><img>I, IGFBP-3, and GHBP were assessed.</p></div><div><h3>Results</h3><p><span><span>Pathological findings of the liver hepatocytes, including cellular swelling, steatosis, apoptosis, necrosis and focal </span>sinusoid congestion were seen in the IH and intermittent hyperoxia groups, and were particularly severe in the 21–12% O</span><sub>2</sub> group during exposure (P14) with no significant improvements during recovery/reoxygenation (P21). These effects were associated with induction of HIF<sub>1α</sub>, and reductions in liver IGF<img>I, IGFBP-3, and GHBP.</p></div><div><h3>Conclusions</h3><p>Exposure to IH or intermittent hyperoxia during the first few weeks of life regardless of resolution in RA or hyperoxia is detrimental to the immature liver. These findings may suggest that interventions to prevent frequent fluctuations in oxygen saturation during early neonatal life remain a high priority.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"72 ","pages":"Article 101559"},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10590175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to growth hormone therapy in ring chromosome 15: Review and evidence from a new case on possible beneficial effect in neurodevelopment","authors":"Selmen Wannes , Ikram El Ahmer , Khouloud Rjiba , Nessrine Jemmali , Hamza Haj Abdallah , Rania Bel Haj , Asma Achour , Hassan Bouzidi , Ali Saad , Soumaya Mougou , Bahri Mahjoub","doi":"10.1016/j.ghir.2023.101550","DOIUrl":"10.1016/j.ghir.2023.101550","url":null,"abstract":"<div><p><span><span>Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and </span>postnatal growth<span><span> retardation, microcephaly<span> and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of </span></span>IGF1R, with limited data </span></span>in patients<span> carrying the most severe form of IGF1R defect, the ring chromosome 15.</span></p></div><div><h3>Subject and method</h3><p><span>We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype<span> and CGH array. We performed a </span></span>systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized.</p></div><div><h3>Results</h3><p>Twelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was −5.1(−5.9/−4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year).</p></div><div><h3>Conclusion</h3><p>GH seems to be effective for r(15) syndrome patients with short stature.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"71 ","pages":"Article 101550"},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of anterior pituitary reserve capacity based on growth hormone response to growth hormone-releasing peptide-2 test in the elderly","authors":"Shinichiro Teramoto , Shigeyuki Tahara , Yujiro Hattori , Akihide Kondo , Akio Morita","doi":"10.1016/j.ghir.2023.101545","DOIUrl":"10.1016/j.ghir.2023.101545","url":null,"abstract":"<div><h3>Objective</h3><p>The growth hormone (GH)-releasing peptide-2 (GHRP-2) test is relatively safe among endocrine stimulation tests for the elderly. We investigated whether anterior pituitary function in elderly patients could be assessed on the basis of GH response to the GHRP-2 test.</p></div><div><h3>Design</h3><p><span>Sixty-five elderly patients aged 65 years and older with non-functioning pituitary neuroendocrine tumor (PitNET) who underwent </span>pituitary surgery and preoperative endocrine stimulation tests were classified into the “GH normal group” and “GH deficiency group” based on GH response to the GHRP-2 test. The baseline characteristics and anterior pituitary function were compared between the groups.</p></div><div><h3>Results</h3><p><span><span>Thirty-two patients were assigned to the GH normal group and 33 to the GH deficiency group. The </span>cortisol<span> and adrenocorticotropic hormone (ACTH) results in the corticotropin-releasing hormone test were significantly higher in the GH normal group than in the GH deficiency group (</span></span><em>p</em> < 0.001). The relationship between the cortisol and ACTH results and the GH response revealed significant correlations (<em>p</em><span> < 0.001). In addition, receiver operating characteristic curve analysis identified that the optimal cut-off point for a peak GH level in the correlation between adrenocortical function and GH response to the GHRP-2 test was 8.08 ng/mL (specificity 0.868, sensitivity 0.852).</span></p></div><div><h3>Conclusion</h3><p>The present study indicated that adrenocortical function was significantly correlated with GH response to the GHRP-2 test in elderly patients before pituitary surgery. For elderly patients with non-functioning PitNET, GH response to the GHRP-2 test may support in diagnosing adrenocortical insufficiency.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"71 ","pages":"Article 101545"},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10575642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Megan Herodes , Nancy Le , Lindsey J. Anderson , Dorota Migula , Gary Miranda , Lauren Paulsen , Jose M. Garcia
{"title":"Metabolic and quality of life effects of growth hormone replacement in patients with TBI and AGHD: A pilot study","authors":"Megan Herodes , Nancy Le , Lindsey J. Anderson , Dorota Migula , Gary Miranda , Lauren Paulsen , Jose M. Garcia","doi":"10.1016/j.ghir.2023.101544","DOIUrl":"10.1016/j.ghir.2023.101544","url":null,"abstract":"<div><h3>Objective</h3><p>Traumatic brain injury (TBI), a common cause of adult growth hormone deficiency (AGHD), affects 20% of Veterans returning from Iraq and Afghanistan (OEF/OIF/OND). Growth hormone replacement therapy (GHRT) improves quality of life (QoL) in AGHD but remains unexplored in this population. This pilot, observational study investigates the feasibility and efficacy of GHRT in AGHD following TBI.</p></div><div><h3>Design</h3><p>In this 6-month study of combat Veterans with AGHD and TBI starting GHRT (<em>N</em> = 7), feasibility (completion rate and rhGH adherence) and efficacy (improvements in self-reported QoL) of GHRT were measured (primary outcomes). Secondary outcomes included body composition, physical and cognitive function, psychological and somatic symptoms, physical activity, IGF-1 levels and safety parameters. It was hypothesized that participants would adhere to GHRT and that QoL would significantly improve after six months.</p></div><div><h3>Results</h3><p>Five subjects (71%) completed all study visits. All patients administered daily rhGH injections, 6 (86%) of whom consistently administered the clinically-prescribed dose. While QoL demonstrated numeric improvement, this change did not reach statistical significance (<em>p</em> = 0.17). Significant improvements were observed in total lean mass (<em>p</em> = 0.02), latissimus dorsi strength (<em>p</em> = 0.05), verbal learning (Trial 1, <em>p</em> = 0.02; Trial 5, <em>p</em> = 0.03), attention (<em>p</em> = 0.02), short-term memory (<em>p</em> = 0.04), and post-traumatic stress disorder (PTSD) symptoms (<em>p</em> = 0.03). Body weight (<em>p</em> = 0.02) and total fat mass (<em>p</em> = 0.03) increased significantly.</p></div><div><h3>Conclusion</h3><p>GHRT is a feasible and well-tolerated intervention for U.S. Veterans with TBI-related AGHD. It improved key areas impacted by AGHD and symptoms of PTSD. Larger, placebo-controlled studies testing the efficacy and safety of this intervention in this population are warranted.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"71 ","pages":"Article 101544"},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10575638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camilla Borghammar , Victoria Boije , Charlotte Becker , Bengt Lindberg , Maria Elfving
{"title":"Prevalence of refractoriness when testing growth hormone levels in children","authors":"Camilla Borghammar , Victoria Boije , Charlotte Becker , Bengt Lindberg , Maria Elfving","doi":"10.1016/j.ghir.2023.101549","DOIUrl":"10.1016/j.ghir.2023.101549","url":null,"abstract":"<div><h3>Objective</h3><p>Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during arginine-insulin-tolerance test (AITT) after a GH peak during a short spontaneous nocturnal profile (SSNP) in children with short stature or low growth velocity.</p></div><div><h3>Design</h3><p>Using SSNP and subsequent AITT, we examined 257 children 4–18 years old (138 (53.7%) males) recruited from three hospitals. Medical records were reviewed retrospectively. Refractory children were defined as a GH peak ≥7 μg/L during SSNP but no GH peak ≥7 μg/L during AITT.</p></div><div><h3>Results</h3><p>In total, 201/257 children had a GH peak ≥7 μg/L at SSNP and/or AITT. Of these, 21.9% were refractory. The proportion of males (<em>p</em> = 0.033) and body mass index (BMI) standard deviation score (SDS) (<em>p</em> = 0.037) were higher in the refractory group than in children with a GH peak ≥7 μg/L during AITT. The median period between last GH peak ≥7 μg/L during SSNP and GH<sub>max</sub> at AITT was 210 (30–390) minutes. The GH<sub>max</sub> at AITT occurred 30 min earlier for children without a peak ≥7 μg/L during the SSNP (<em>p</em> = 0.004). The number of refractoriness differed somewhat between the hospitals (<em>p</em> = 0.025).</p></div><div><h3>Conclusions</h3><p>Many children with short stature were refractory at testing; among them we found few clinical characteristics. Refractoriness might be influenced by some differences in procedure, but needs to be considered when evaluating GH response in children.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"71 ","pages":"Article 101549"},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Administration of insulin like growth factor I (IGFI) lowers serum lipoprotein(a)-impact on atherosclerotic cardiovascular disease","authors":"Zvi Laron , Haim Werner","doi":"10.1016/j.ghir.2023.101548","DOIUrl":"10.1016/j.ghir.2023.101548","url":null,"abstract":"<div><p><span>Insulin like growth factor I (IGF</span><img><span>I) secreted by the liver upon stimulation by pituitary growth hormone (GH) acts as the most important growth stimulating hormone in children. The present review presents evidence that among its additional metabolic effects, IGF-I suppresses the synthesis of lipoprotein(a) [Lp(a)], an independent risk factor for atherosclerotic cardiovascular disease. In view of this property, it is suggested that the addition of IGF-I to the armamentarium of hyperlipoproteinemia<span> treatment should be considered.</span></span></p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"71 ","pages":"Article 101548"},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel Barker , Kalina Biernacka , Georgina Kingshott , Alex Sewell , Paida Gwiti , Richard M. Martin , J. Athene Lane , Lucy McGeagh , Anthony Koupparis , Edward Rowe , Jon Oxley , Claire M. Perks , Jeff M.P. Holly
{"title":"Associations of CTCF and FOXA1 with androgen and IGF pathways in men with localized prostate cancer","authors":"Rachel Barker , Kalina Biernacka , Georgina Kingshott , Alex Sewell , Paida Gwiti , Richard M. Martin , J. Athene Lane , Lucy McGeagh , Anthony Koupparis , Edward Rowe , Jon Oxley , Claire M. Perks , Jeff M.P. Holly","doi":"10.1016/j.ghir.2023.101533","DOIUrl":"10.1016/j.ghir.2023.101533","url":null,"abstract":"<div><h3>Aims</h3><p>To examine associations between the transcription factors CCCTC-binding factor (CTCF) and forkhead box protein A1<span><span> (FOXA1) and the androgen receptor (AR) and their association with components of the insulin-like growth factor (IGF)-pathway in a cohort of men with localized </span>prostate cancer.</span></p></div><div><h3>Methods</h3><p><span>Using prostate tissue samples collected during the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) trial (</span><em>N</em><span><span> = 70 to 92, depending on section availability), we assessed the abundance of CTCF, </span>FOXA1, AR, IGFIR, p-mTOR, PTEN and IGFBP-2 proteins using a modified version of the Allred scoring system. Validation studies were performed using large, publicly available datasets (TCGA) (</span><em>N</em> = 489).</p></div><div><h3>Results</h3><p>We identified a strong correlation between CTCF and AR staining with benign prostate tissue. CTCF also strongly associated with the IGF<img>IR, with PTEN and with phospho-mTOR. FOXA1 was also correlated with staining for the IGF-IR, with IGFBP-2 and with staining for activated phosphor-mTOR. The staining for the IGF-IR was strongly correlated with the AR.</p></div><div><h3>Conclusion</h3><p>Our findings emphasise the close and complex links between the endocrine controls, well known to play an important role in prostate cancer, and the transcription factors implicated by the recent genetic evidence.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"69 ","pages":"Article 101533"},"PeriodicalIF":1.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10040202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyungchul Song , Mo Kyung Jung , Jun Suk Oh , Su Jin Kim , Han Saem Choi , Myeongseob Lee , Junghwan Suh , Ahreum Kwon , Hyun Wook Chae , Ho-Seong Kim
{"title":"Comparison of growth response and adverse reaction according to growth hormone dosing strategy for children with short stature: LG Growth Study","authors":"Kyungchul Song , Mo Kyung Jung , Jun Suk Oh , Su Jin Kim , Han Saem Choi , Myeongseob Lee , Junghwan Suh , Ahreum Kwon , Hyun Wook Chae , Ho-Seong Kim","doi":"10.1016/j.ghir.2023.101531","DOIUrl":"10.1016/j.ghir.2023.101531","url":null,"abstract":"<div><h3>Objective</h3><p>Growth hormone (GH) dosage in children is conventionally determined either by body weight (BW) or body surface area (BSA). However, there is no consensus on the calculation method for proper GH treatment dose. We aimed to compare growth response and adverse reactions between BW- and BSA-based GH treatment doses for children with short statures.</p></div><div><h3>Design</h3><p>Data from 2284 GH-treated children were analyzed. Distributions of BW- and BSA-based GH treatment doses and their association with growth response parameters, including changes in height, height standard deviation score (SDS), body mass index (BMI), and safety parameters, such as changes in insulin-like growth factor (IGF)-I SDS and adverse events, were investigated.</p></div><div><h3>Results</h3><p><span><span>The mean BW-based doses were close to the recommended dose's<span> upper limit in participants with GH deficiency and </span></span>idiopathic short stature, while they were below the recommended dose </span>in patients<span> with Turner syndrome (TS). As age and BW increased, BW-based dose decreased, whereas BSA-based dose increased. Gain in height SDS was positively associated with BW-based dose in the TS group and negatively associated with BW in all groups. Despite having a lower BW-based dose, the overweight/obese groups had a higher BSA-based dose and higher frequencies of children with high IGF-I and adverse events than those of the normal-BMI group.</span></p></div><div><h3>Conclusions</h3><p>In children of older age or with high BW, BW-based doses can be overdosed in terms of BSA. and BW-based dose positively correlated with height gain only in the TS group. BSA-based doses represent an alternative dosing strategy in children who are overweight/obese.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"69 ","pages":"Article 101531"},"PeriodicalIF":1.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9666379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fengping Sun , Liqin Chao , Junxia Zhang , Xiaoli Pan
{"title":"Exercise combined with lysine-inositol vitamin B12 promotes height growth in children with idiopathic short stature","authors":"Fengping Sun , Liqin Chao , Junxia Zhang , Xiaoli Pan","doi":"10.1016/j.ghir.2023.101535","DOIUrl":"10.1016/j.ghir.2023.101535","url":null,"abstract":"<div><h3>Objective</h3><p>This study was aimed to systematically determine the effect of exercise combined with lysine-inositol vitamin B12<span> (VB12) therapy on the height of children with idiopathic short stature (ISS).</span></p></div><div><h3>Methods</h3><p>Sixty children with ISS were randomly divided into observation and control groups (<em>N</em><span> = 30). Each group was given lysine-inositol VB12 oral solution (10 mL bid). Simultaneously, the observation group exercised following the “ISS exercise instruction sheet”. The height (H), growth velocity (GV), height standard deviation score (HtSDS) and other indicators were compared after 6 and 12 months of intervention, respectively. After 12 months of intervention, the biochemical indicators of the two groups, together with the correlation between the average days of exercise per week and average minutes of exercise per day, GV and serum growth hormone were analyzed.</span></p></div><div><h3>Results</h3><p><span><span>After 6 and 12 months of treatment, the GV, serum </span>GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels in the observation group were significantly higher than those in the control group, and HtSDS was significantly lower than that in the control group (</span><em>P</em><0.01). After 12 months of treatment, the height of the observation group was significantly higher than that of the control group (<em>P</em><0.05). There was no significant difference in the biochemical indicators between two groups (<em>P</em>>0.05). Average days of exercise per week and average minutes of exercise per day were positively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were negatively correlated. Average minutes of exercise per day were negatively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were positively correlated.</p></div><div><h3>Conclusion</h3><p>Regular and moderate stretching exercises combined with lysine-inositol VB12 can effectively promote height growth of children with ISS, which is clinically safe. The mechanism promotes serum GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":"69 ","pages":"Article 101535"},"PeriodicalIF":1.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}