Pub Date : 2024-02-21DOI: 10.1016/j.ghir.2024.101574
Xiaoyan Zhu , Fei Liang , Jieyun Yin , Xiaoliang Li , Lai Jiang , Yan Gao , Yan Lu , Yihe Hu , Ningbin Dai , Jian Su , Zhuoqiao Yang , Mengxin Yao , Yue Xiao , Wenxin Ge , Yue Zhang , Yi Zhong , Jun Zhang , Ming Wu
Objective
Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients.
Design
A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively.
Results
Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06–5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7.
Conclusion
IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.
{"title":"Duration-specific association between plasma IGFBP7 levels and diabetic complications in patients with type 2 diabetes mellitus","authors":"Xiaoyan Zhu , Fei Liang , Jieyun Yin , Xiaoliang Li , Lai Jiang , Yan Gao , Yan Lu , Yihe Hu , Ningbin Dai , Jian Su , Zhuoqiao Yang , Mengxin Yao , Yue Xiao , Wenxin Ge , Yue Zhang , Yi Zhong , Jun Zhang , Ming Wu","doi":"10.1016/j.ghir.2024.101574","DOIUrl":"10.1016/j.ghir.2024.101574","url":null,"abstract":"<div><h3>Objective</h3><p>Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients.</p></div><div><h3>Design</h3><p>A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively.</p></div><div><h3>Results</h3><p>Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06–5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7.</p></div><div><h3>Conclusion</h3><p>IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139921618","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}
Growth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility after GH replacement. The frequency of GH deficiency is not established in patients diagnosed with unexplained infertility. Here, we aim to present the prevalence of GH deficieny in this patient group.
Methods
We included patients diagnosed with unexplained infertility throughout 18 months. Insulin tolerance test (ITT) and glucagon stimulation tests (GST) were performed and insufficient response to both tests was required for the diagnosis of GH deficiency.
Results
Twenty-five patients were included in the study, the mean age was 27.4 ± 4.5 years and the median duration of infertility was 60 months (min:14, max:120). Two patients were GH deficient according to GST and 14 to ITT. Two patients (8%) showed lack of response on both tests and were diagnosed with GH deficiency.
Conclusion
The rate of GH deficiency among women with unexplained infertility was 8% in this preliminary study. There is need for further studies with larger patient groups to verify the results.
{"title":"Evaluation of growth hormone deficiency in women with unexplained infertility","authors":"Mehmet Serif Ortac , Aysa Hacioglu , Semih Zeki Uludag , Zuleyha Karaca , Kursad Unluhizarci , Fahrettin Kelestimur , Fatih Tanriverdi","doi":"10.1016/j.ghir.2024.101571","DOIUrl":"10.1016/j.ghir.2024.101571","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Growth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility after GH replacement. The frequency of GH deficiency is not established </span>in patients diagnosed with unexplained infertility. Here, we aim to present the prevalence of GH deficieny in this patient group.</p></div><div><h3>Methods</h3><p>We included patients diagnosed with unexplained infertility throughout 18 months. Insulin tolerance test<span> (ITT) and glucagon stimulation tests (GST) were performed and insufficient response to both tests was required for the diagnosis of GH deficiency.</span></p></div><div><h3>Results</h3><p>Twenty-five patients were included in the study, the mean age was 27.4 ± 4.5 years and the median duration of infertility was 60 months (min:14, max:120). Two patients were GH deficient according to GST and 14 to ITT. Two patients (8%) showed lack of response on both tests and were diagnosed with GH deficiency.</p></div><div><h3>Conclusion</h3><p>The rate of GH deficiency among women with unexplained infertility was 8% in this preliminary study. There is need for further studies with larger patient groups to verify the results.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562519","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}
Pub Date : 2024-02-01DOI: 10.1016/j.ghir.2024.101573
Craig Alter , Margaret Boguszewski , David Clemmons , Georgiana A. Dobri , Mitchell E. Geffner , Nicky Kelepouris , Bradley S. Miller , Richard Oh , Heidi Shea , Kevin C.J. Yuen
Objective
Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition.
Design
An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients.
Results/conclusions
Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.
{"title":"Insights from an advisory board: Facilitating transition of care into adulthood in brain cancer survivors with acquired pediatric growth hormone deficiency","authors":"Craig Alter , Margaret Boguszewski , David Clemmons , Georgiana A. Dobri , Mitchell E. Geffner , Nicky Kelepouris , Bradley S. Miller , Richard Oh , Heidi Shea , Kevin C.J. Yuen","doi":"10.1016/j.ghir.2024.101573","DOIUrl":"10.1016/j.ghir.2024.101573","url":null,"abstract":"<div><h3>Objective</h3><p>Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition.</p></div><div><h3>Design</h3><p>An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients.</p></div><div><h3>Results/conclusions</h3><p>Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1096637424000030/pdfft?md5=096342c1834a83d56df592c8537ea9c5&pid=1-s2.0-S1096637424000030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139897152","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}
GATA2 is a key transcription factor involved in the differentiation and determination of thyrotrophs and gonadotrophs in pituitary and hematopoietic development. However, studies on the upstream ligands of the GATA2 signal transduction pathway have been limited. To identify upstream ligands, we examined growth hormone (GH) as a plausible stimulator.
Design
We evaluated GH-induced GATA2 expression in murine TtT/GF thyrotrophic pituitary tumor cells and its direct impact on the GHR/JAK/STAT5 pathway using a combination of a reporter assay, real-time quantitative polymerase chain reaction, and western blotting.
Results
GATA2 expression increased with activated STAT5B in a dose-dependent manner and was inhibited by a STAT5 specific inhibitor. Moreover, we found functional STAT5B binding site consensus sequences at −359 bp in the GATA2 promoter region.
Conclusion
These findings suggest that GH directly stimulates GATA2 via the GHR/JAK/STAT pathway and participates in various developmental phenomena mediated by GATA2.
目的GATA2是一种关键的转录因子,参与垂体和造血发育过程中甲状腺和促性腺激素的分化和决定。然而,有关 GATA2 信号转导通路上游配体的研究还很有限。为了确定上游配体,我们将生长激素(GH)作为一种可能的刺激物进行了研究。结果GATA2的表达以剂量依赖的方式随活化的STAT5B而增加,并受到STAT5特异性抑制剂的抑制。此外,我们在 GATA2 启动子区域的 -359 bp 处发现了功能性 STAT5B 结合位点共识序列。
{"title":"Growth hormone directly stimulates GATA2 expression","authors":"Mana Mitsutani , Midori Matsushita , Mei Yokoyama , Ayumu Morita , Hiromi Hano , Tomomi Fujikawa , Tetsuya Tagami , Kenji Moriyama","doi":"10.1016/j.ghir.2024.101572","DOIUrl":"10.1016/j.ghir.2024.101572","url":null,"abstract":"<div><h3>Objective</h3><p><span>GATA2 is a key transcription factor involved in the differentiation and determination of thyrotrophs and </span>gonadotrophs<span> in pituitary and hematopoietic development. However, studies on the upstream ligands of the GATA2 signal transduction pathway have been limited. To identify upstream ligands, we examined growth hormone (GH) as a plausible stimulator.</span></p></div><div><h3>Design</h3><p>We evaluated GH-induced GATA2 expression in murine TtT/GF thyrotrophic pituitary tumor<span> cells and its direct impact on the GHR/JAK/STAT5 pathway using a combination of a reporter assay, real-time quantitative polymerase chain reaction, and western blotting.</span></p></div><div><h3>Results</h3><p>GATA2 expression increased with activated STAT5B<span> in a dose-dependent manner and was inhibited by a STAT5 specific inhibitor. Moreover, we found functional STAT5B binding site consensus sequences at −359 bp in the GATA2 promoter region.</span></p></div><div><h3>Conclusion</h3><p>These findings suggest that GH directly stimulates GATA2 via the GHR/JAK/STAT pathway and participates in various developmental phenomena mediated by GATA2.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562520","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}
Pub Date : 2023-10-01DOI: 10.1016/j.ghir.2023.101558
Eran Lavi , Amitay Cohen , Abdulsalam Abu Libdeh , Reuven Tsabari , David Zangen , Talya Dor
Objective
To evaluate the outcome of recombinant human Growth Hormone (rhGH) therapy in patients with Duchene Muscular Dystrophy (DMD) and glucocorticoid treatment with compromised growth.
Design
Four DMD patients on Deflzacort 0.6–0.85 mg/kg/day or prednisolone 0.625 mg/kg/day recieved rhGH (0.24 mg/kg/week) for 6–18 months. Primary outcomes were Growth velocity and Height for age Z-scores (Height SD).
Results
Growth velocity increased from 0 to 3.25 cm/year prior to GH therapy to 3.3–7.8 cm/year over a period of 6–18 months. The typical Height SD decline in DMD was reversed in two patients and blunted in one. No adverse events or deterioration in cardiac or respiratory parameters were associated with the rhGH treatment.
Conclusions
rhGH appears to be safe and efficient in promoting growth of patients with glucocorticoid induced growth failure in DMD.
{"title":"Growth hormone therapy for children with Duchenne muscular dystrophy and glucocorticoid induced short stature","authors":"Eran Lavi , Amitay Cohen , Abdulsalam Abu Libdeh , Reuven Tsabari , David Zangen , Talya Dor","doi":"10.1016/j.ghir.2023.101558","DOIUrl":"10.1016/j.ghir.2023.101558","url":null,"abstract":"<div><h3>Objective</h3><p><span><span>To evaluate the outcome of recombinant human Growth Hormone (rhGH) therapy </span>in patients<span> with Duchene Muscular Dystrophy (DMD) and </span></span>glucocorticoid<span> treatment with compromised growth.</span></p></div><div><h3>Design</h3><p><span>Four DMD patients on Deflzacort 0.6–0.85 mg/kg/day or prednisolone 0.625 mg/kg/day recieved rhGH (0.24 mg/kg/week) for 6–18 months. Primary outcomes were Growth velocity and Height for age </span><em>Z</em>-scores (Height SD).</p></div><div><h3>Results</h3><p>Growth velocity increased from 0 to 3.25 cm/year prior to GH therapy to 3.3–7.8 cm/year over a period of 6–18 months. The typical Height SD decline in DMD was reversed in two patients and blunted in one. No adverse events or deterioration in cardiac or respiratory parameters were associated with the rhGH treatment.</p></div><div><h3>Conclusions</h3><p>rhGH appears to be safe and efficient in promoting growth of patients with glucocorticoid induced growth failure in DMD.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10177776","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}
Pub Date : 2023-10-01DOI: 10.1016/j.ghir.2023.101561
Tathyana Benetis Piau, Aline de Queiroz Rodrigues, Fernanda Paulini
The role of the insulin-like growth factor (IGF) system has attracted close attention. The activity of IGF binding proteins (IGFBPs) within the ovary has not been fully elucidated to date. These proteins bind to IGF with an equal, or greater, affinity than to the IGF1 receptor, thus being in the main position to regulate IGF signalling, in addition to extending the half-life of IGFs within the bloodstream and promoting IGF storage in specific tissue niches. IGF1 has an important part in cell proliferation, differentiation and apoptosis. Considering the importance of IGFs in oocyte maturation, this review sought to elucidate aspects including: IGF production mechanisms; constituent members of their family and their respective functions; the role that these factors play during folliculogenesis, together with their functions during oocyte maturation and apoptosis, and their performance during luteal development. This review also explores the role of IGFs in biotechnological applications, focusing specifically on animal genetic gain.
{"title":"Insulin-like growth factor (IGF) performance in ovarian function and applications in reproductive biotechnologies","authors":"Tathyana Benetis Piau, Aline de Queiroz Rodrigues, Fernanda Paulini","doi":"10.1016/j.ghir.2023.101561","DOIUrl":"https://doi.org/10.1016/j.ghir.2023.101561","url":null,"abstract":"<div><p><span>The role of the insulin-like growth factor (IGF) system has attracted close attention. The activity of IGF binding proteins (IGFBPs) within the ovary has not been fully elucidated to date. These proteins bind to IGF with an equal, or greater, affinity than to the </span>IGF1<span><span><span> receptor, thus being in the main position to regulate IGF signalling, in addition to extending the half-life of IGFs within the bloodstream and promoting IGF storage in specific tissue niches. IGF1 has an important part in cell proliferation<span>, differentiation and apoptosis. Considering the importance of IGFs in </span></span>oocyte maturation, this review sought to elucidate aspects including: IGF production mechanisms; constituent members of their family and their respective functions; the role that these factors play during </span>folliculogenesis<span>, together with their functions during oocyte maturation and apoptosis, and their performance during luteal development. This review also explores the role of IGFs in biotechnological applications, focusing specifically on animal genetic gain.</span></span></p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138549364","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}
Pub Date : 2023-10-01DOI: 10.1016/j.ghir.2023.101560
Sophia Krombholz , Andreas Thomas , Philippe Delahaut , Martin Bidlingmaier , Katharina Schilbach , Geoffrey Miller , Mario Thevis
Objective
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.
Design
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.
Results
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 (R2 > 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.
Conclusion
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.
{"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":null,"pages":null},"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}
Pub Date : 2023-10-01DOI: 10.1016/j.ghir.2023.101559
Charles L. Cai , Matthew Marcelino , Jacob V. Aranda , Kay D. Beharry
Objective
Extremely low gestational age neonates requiring oxygen therapy for chronic lung disease experience repeated fluctuations in arterial oxygen saturation, or intermittent hypoxia (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, IGF binding protein (BP)-3, and growth hormone binding protein (GHBP), regardless of resolution in normoxia or hyperoxia between episodes.
Design
Newborn rats on the first day of life (P0) were exposed to two IH paradigms: 1) hyperoxia (50% O2) with brief hypoxia (12% O2); or 2) normoxia (21% O2) with hypoxia (12% O2); intermittent hypoxia (50% O2/21% O2); hyperoxia only (50% O2); or room air (RA, 21% O2). Pups were euthanized on P14 or placed in RA until P21. Controls remained in RA from P0-P21. Growth, liver histopathology, apoptosis, IGFI, IGFBP-3, and GHBP were assessed.
Results
Pathological findings of the liver hepatocytes, including cellular swelling, steatosis, apoptosis, necrosis and focal sinusoid congestion were seen in the IH and intermittent hyperoxia groups, and were particularly severe in the 21–12% O2 group during exposure (P14) with no significant improvements during recovery/reoxygenation (P21). These effects were associated with induction of HIF1α, and reductions in liver IGFI, IGFBP-3, and GHBP.
Conclusions
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.
{"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":null,"pages":null},"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}
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 postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15.
Subject and method
We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a 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.
Results
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).
Conclusion
GH seems to be effective for r(15) syndrome patients with short stature.
{"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":null,"pages":null},"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}
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.
Design
Sixty-five elderly patients aged 65 years and older with non-functioning pituitary neuroendocrine tumor (PitNET) who underwent 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.
Results
Thirty-two patients were assigned to the GH normal group and 33 to the GH deficiency group. The cortisol 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 (p < 0.001). The relationship between the cortisol and ACTH results and the GH response revealed significant correlations (p < 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).
Conclusion
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.
{"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":null,"pages":null},"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}