Endocrinology and Metabolism

Review Articles

Adrenal gland
The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Factor-1, and Insulin: Eline C. Nijenhuis-Noort, Kirsten A. Berk, Sebastian J. C. M. M. Neggers, Aart J. van der Lely; Endocrinol Metab. 2024;39(1):83-89. Published online January 9, 2024; DOI: https://doi.org/10.3803/EnM.2024.101

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This review intends to provide the reader with a practical overview of several (patho)physiological conditions in which knowledge of the interplay between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin is important. This might help treating physicians in making the right decisions on how to intervene and improve metabolism for the benefit of patients, and to understand why and how metabolism responds in their specific cases. We will specifically address the interplay between GH, IGF-1, and insulin in type 1 and 2 diabetes mellitus, liver cirrhosis, and acromegaly as examples in which this knowledge is truly necessary.

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Signaling pathways and targeted therapies in Ewing sarcoma
Ke Jia, Li Cao, Yihan Yu, Doudou Jing, Wei Wu, Brian Andrew Van Tine, Zengwu Shao
Pharmacology & Therapeutics.2025; 266: 108765. CrossRef
IGF-1 and IGF-2 as Molecules Linked to Causes and Consequences of Obesity from Fetal Life to Adulthood: A Systematic Review
Justyna Szydlowska-Gladysz, Adrianna Edyta Gorecka, Julia Stepien, Izabela Rysz, Iwona Ben-Skowronek
International Journal of Molecular Sciences.2024; 25(7): 3966. CrossRef
Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial
Benjamin D. Horne, Jeffrey L. Anderson, Heidi T. May, Tami L. Bair, Viet T. Le, Leslie Iverson, Kirk U. Knowlton, Joseph B. Muhlestein
npj Metabolic Health and Disease.2024;[Epub] CrossRef
Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies
Jie Miao, Yanli Zhang, Chen Su, Qiandan Zheng, Junhong Guo
Molecular Neurobiology.2024;[Epub] CrossRef
GHRH in diabetes and metabolism
Charlotte Steenblock, Stefan R. Bornstein
Reviews in Endocrine and Metabolic Disorders.2024;[Epub] CrossRef
Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin
Kevin C. J. Yuen, Rikke Hjortebjerg, Ashok Ainkaran Ganeshalingam, David R. Clemmons, Jan Frystyk
Frontiers in Endocrinology.2024;[Epub] CrossRef
Expanding the Clinical and Mutational Spectrum of Biallelic POC1A Variants: Characterization of Four Patients and a Comprehensive Review of POC1A‐Related Phenotypes
Umut Altunoglu, Gozde Tutku Turgut, Esin Karakılıç Özturan, Tuğba Kalaycı, Mert Kaya, Güven Toksoy, Firdevs Baş, Hülya Kayserili, Feyza Darendeliler
Clinical Genetics.2024;[Epub] CrossRef

Calcium & bone metabolism
Acromegaly and Bone: An Update: Andrea Giustina; Endocrinol Metab. 2023;38(6):655-666. Published online December 22, 2023; DOI: https://doi.org/10.3803/EnM.2023.601

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Since our discovery in 2006 that acromegaly is associated with an increased risk of vertebral fractures, many authors have confirmed this finding in both cross-sectional and prospective studies. Due to the high epidemiological and clinical impact of this newly discovered comorbidity of acromegaly, this topic has progressively become more important and prominent over the years, and the pertinent literature has been enriched by new findings on the pathophysiology and treatment. The aim of this narrative review was to discuss these novel findings, integrating them with the seminal observations, in order to give the reader an updated view of how the field of acromegaly and bone is developing, from strong clinical observations to a mechanistic understanding and possible prevention and treatment.

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New insights into the vitamin D/PTH axis in endocrine-driven metabolic bone diseases
Luigi di Filippo, John P. Bilezikian, Ernesto Canalis, Umberto Terenzi, Andrea Giustina
Endocrine.2024; 85(3): 1007. CrossRef
Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot single center experience
Sabrina Chiloiro, Antonella Giampietro, Amato Infante, Pier Paolo Mattogno, Liverana Lauretti, Alessandro Olivi, Laura De Marinis, Alfredo Pontecorvi, Francesco Doglietto, Antonio Bianchi
Pituitary.2024; 27(3): 303. CrossRef
Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE)
Andrea Giustina, M. M. Uygur, S. Frara, A. Barkan, N. R. Biermasz, P. Chanson, P. Freda, M. Gadelha, L. Haberbosch, U. B. Kaiser, S. Lamberts, E. Laws, L. B. Nachtigall, V. Popovic, M. Reincke, A. J. van der Lely, J. A. H. Wass, S. Melmed, F. F. Casanueva
Pituitary.2024; 27(4): 381. CrossRef
Vertebral fractures in patients with non-functioning pituitary adenomas - a new frontier?
Nicholas A. Tritos
Pituitary.2024; 27(4): 311. CrossRef
Suspected silent pituitary somatotroph neuroendocrine tumor associated with acromegaly-like bone disorders: a case report
Tongxin Xiao, Xinxin Mao, Ou Wang, Yong Yao, Kan Deng, Huijuan Zhu, Lian Duan
BMC Endocrine Disorders.2024;[Epub] CrossRef
Skeletal fragility in pituitary disease: how can we predict fracture risk?
Fabio Bioletto, Alessandro Maria Berton, Marco Barale, Luigi Simone Aversa, Lorenzo Sauro, Michela Presti, Francesca Mocellini, Noemi Sagone, Ezio Ghigo, Massimo Procopio, Silvia Grottoli
Pituitary.2024; 27(6): 789. CrossRef
Vitamin D in pituitary driven osteopathies
Sabrina Chiloiro, Flavia Costanza, Elena Riccardi, Antonella Giampietro, Laura De Marinis, Antonio Bianchi, Alfredo Pontecorvi, Andrea Giustina
Pituitary.2024; 27(6): 847. CrossRef
GH receptor polymorphisms guide second-line therapies to prevent acromegaly skeletal fragility: preliminary results of a pilot study
Sabrina Chiloiro, Flavia Costanza, Antonella Giampietro, Amato Infante, Pier Paolo Mattogno, Flavia Angelini, Consolato Gullì, Liverana Lauretti, Mario Rigante, Alessandro Olivi, Laura De Marinis, Francesco Doglietto, Antonio Bianchi, Alfredo Pontecorvi
Frontiers in Endocrinology.2024;[Epub] CrossRef
Vitamin D and hip protectors in osteosarcopenia: a combined hip fracture preventing approach
Alessandro Giustina, Andrea Giustina
Reviews in Endocrine and Metabolic Disorders.2024;[Epub] CrossRef
Growth hormone and bone: a basic perspective
Simona Bolamperti, Isabella Villa, Luigi di Filippo
Pituitary.2024; 27(6): 745. CrossRef
Approach to the patient with controlled acromegaly and acromegalic arthropathy: clinical diagnosis and management
Iris C. M. Pelsma, Herman M. Kroon, Cornelie D. Andela, Enrike M. J. van der Linden, Margreet Kloppenburg, Nienke R. Biermasz, Kim M. J. A. Claessen
Pituitary.2024; 27(6): 824. CrossRef
Modern approach to bone comorbidity in prolactinoma
Meliha Melin Uygur, Sara Menotti, Simona Santoro, Andrea Giustina
Pituitary.2024; 27(6): 802. CrossRef
Novel approach to bone comorbidity in resistant acromegaly
Stefano Frara, Matteo Acanfora, Vincenzo Franzese, Maria Luisa Brandi, Marco Losa, Andrea Giustina
Pituitary.2024; 27(6): 813. CrossRef

Songwon Lecture 2022

Hypothalamus and pituitary gland
Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine: Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2023;38(5):463-471. Published online October 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1820

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The clinical characteristics and prognoses of acromegaly vary among patients. Assessment of current and novel predictors can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and a reduction in the increased morbidity and mortality associated with acromegaly. Despite advances in the diagnosis and treatment of acromegaly, its pathophysiology remains unclear. Recent advancements in multiomics technologies, including genomics, transcriptomics, proteomics, metabolomics, and radiomics, have offered new opportunities to unravel the complex pathophysiology of acromegaly. This review comprehensively explores the emerging role of multiomics approaches in elucidating the molecular landscape of acromegaly. We discuss the potential implications of multiomics data integration in the development of novel diagnostic tools, identification of therapeutic targets, and the prospects of precision medicine in acromegaly management. By integrating diverse omics datasets, these approaches can provide valuable insights into disease mechanisms, facilitate the identification of diagnostic biomarkers, and identify potential therapeutic targets for precision medicine in the management of acromegaly.

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“Micromegaly”: Acromegaly with apparently normal GH, an entity on its own?
Lucio Vilar, Luciana Ansaneli Naves, Manoel Ricardo Alves Martins, Antônio Ribeiro-Oliveira Jr
Best Practice & Research Clinical Endocrinology & Metabolism.2024; 38(3): 101878. CrossRef

Review Article

Hypothalamus and Pituitary Gland
Independent Skeletal Actions of Pituitary Hormones: Se-Min Kim, Farhath Sultana, Funda Korkmaz, Daria Lizneva, Tony Yuen, Mone Zaidi; Endocrinol Metab. 2022;37(5):719-731. Published online September 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.1573

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Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector glands axis. Bone cells—osteoblasts and osteoclasts—express receptors for growth hormone, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin, and vasopressin. Independent skeletal actions of pituitary hormones on bone have been studied using genetically modified mice with haploinsufficiency and by activating or inactivating the receptors pharmacologically, without altering systemic effector hormone levels. On another front, the discovery of a TSH variant (TSH-βv) in immune cells in the bone marrow and skeletal action of FSHβ through tumor necrosis factor α provides new insights underscoring the integrated physiology of bone-immune-endocrine axis. Here we discuss the interaction of each pituitary hormone with bone and the potential it holds in understanding bone physiology and as a therapeutic target.

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Cushing’s disease and bone
Aleksandra Zdrojowy-Wełna, Barbara Stachowska, Marek Bolanowski
Pituitary.2024; 27(6): 837. CrossRef
Skeletal fragility in pituitary disease: how can we predict fracture risk?
Fabio Bioletto, Alessandro Maria Berton, Marco Barale, Luigi Simone Aversa, Lorenzo Sauro, Michela Presti, Francesca Mocellini, Noemi Sagone, Ezio Ghigo, Massimo Procopio, Silvia Grottoli
Pituitary.2024; 27(6): 789. CrossRef
Role of oxytocin in bone
Tianming Wang, Jianya Ye, Yongqiang Zhang, Jiayi Li, Tianxiao Yang, Yufeng Wang, Xiao Jiang, Qingqiang Yao
Frontiers in Endocrinology.2024;[Epub] CrossRef
Plasma proteomic profiles reveal proteins and three characteristic patterns associated with osteoporosis: A prospective cohort study
Yi Zheng, Jincheng Li, Yucan Li, Jiacheng Wang, Chen Suo, Yanfeng Jiang, Li Jin, Kelin Xu, Xingdong Chen
Journal of Advanced Research.2024;[Epub] CrossRef
Modern approach to bone comorbidity in prolactinoma
Meliha Melin Uygur, Sara Menotti, Simona Santoro, Andrea Giustina
Pituitary.2024; 27(6): 802. CrossRef
New tools for bone health assessment in secreting pituitary adenomas
Meliha Melin Uygur, Stefano Frara, Luigi di Filippo, Andrea Giustina
Trends in Endocrinology & Metabolism.2023; 34(4): 231. CrossRef
A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility
Dongjin Lee, Moon Ahn
Metabolites.2023; 13(3): 372. CrossRef
The mechanism of oxytocin and its receptors in regulating cells in bone metabolism
Liu Feixiang, Feng Yanchen, Li Xiang, Zhang Yunke, Miao Jinxin, Wang Jianru, Lin Zixuan
Frontiers in Pharmacology.2023;[Epub] CrossRef
To investigate the mechanism of Yiwei Decoction in the treatment of premature ovarian insufficiency-related osteoporosis using transcriptomics, network pharmacology and molecular docking techniques
Weisen Fan, Yan Meng, Jing Zhang, Muzhen Li, Yingjie Zhang, Xintian Qu, Xin Xiu
Scientific Reports.2023;[Epub] CrossRef

Original Article

Hypothalamus and Pituitary Gland
Metabolic Impacts of Discontinuation and Resumption of Recombinant Human Growth Hormone Treatment during the Transition Period in Patients with Childhood-Onset Growth Hormone Deficiency: Yun Jeong Lee, Yunha Choi, Han-Wook Yoo, Young Ah Lee, Choong Ho Shin, Han Saem Choi, Ho-Seong Kim, Jae Hyun Kim, Jung Eun Moon, Cheol Woo Ko, Moon Bae Ahn, Byung-Kyu Suh, Jin-Ho Choi; Endocrinol Metab. 2022;37(2):359-368. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1384

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Background
Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.
Methods
This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.
Results
Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.
Conclusion
GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Citations

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Impact of non-weight-dependent low-dose somatropin on bone accrual in childhood-onset GH deficient in the transition: an 18-month randomized controlled trial
Valesca Mansur Kuba, Antonia B.S. Castro, Cláudio Leone, Durval Damiani
Jornal de Pediatria.2025;[Epub] CrossRef
Ghrelin regulating liver activity and its potential effects on liver fibrosis and Echinococcosis
Jiang Zhu, Tanfang Zhou, Meng Menggen, Kalibixiati Aimulajiang, Hao Wen
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
Composición de la microbiota en pacientes con déficit de hormona de crecimiento antes y después de recibir tratamiento
Patricia García Navas, María Yolanda Ruíz del Prado, Pablo Villoslada Blanco, Emma Recio Fernández, María Ruíz del Campo, Patricia Pérez Matute
Anales de Pediatría.2024; 100(6): 404. CrossRef
Composition of the microbiota in patients with growth hormone deficiency before and after treatment with growth hormone
Patricia García Navas, María Yolanda Ruíz del Prado, Pablo Villoslada Blanco, Emma Recio Fernández, María Ruíz del Campo, Patricia Pérez Matute
Anales de Pediatría (English Edition).2024; 100(6): 404. CrossRef
Clinical Management of Postoperative Growth Hormone Deficiency in Hypothalamic-Pituitary Tumors
Pedro Iglesias
Journal of Clinical Medicine.2024; 13(15): 4307. CrossRef
An Overview of Cardiovascular Risk in Pituitary Disorders
Georgia Ntali, Vyron Markussis, Alexandra Chrisoulidou
Medicina.2024; 60(8): 1241. CrossRef
The role of IGF1 in determining body composition in children and adolescents with growth hormone deficiency and those with idiopathic short stature
Hussein Zaitoon, Michal Yackobovitch-Gavan, Eyas Midlej, Adi Uretzky, Irina Laurian, Anna Dorfman, Hagar Interator, Yael Lebenthal, Avivit Brener
Endocrine.2024; 86(3): 1110. CrossRef
Policy for transitioning childhood-onset growth hormone deficiency from pediatric to adult endocrine care in Belgium
Willem Staels, Jean De Schepper, Marianne Becker, Philippe Lysy, Daniel Klink, Karl Logghe, Marieken den Brinker, Anne Rochtus, Bruno Lapauw, Martine Cools, Orsalia Alexopoulou, Marie Bex, Bernard Corvilain, Laurent Crenier, Christophe De Block, Julian Do
Frontiers in Endocrinology.2024;[Epub] CrossRef
Transition Period and Young Adulthood in Patients with Childhood Onset Growth Hormone Deficiency (COGHD): Impact of Growth Hormone Replacement on Bone Mass and Body Composition
Mirjana Doknic, Marko Stojanovic, Aleksandra Markovic
International Journal of Molecular Sciences.2024; 25(19): 10313. CrossRef
Baseline Clinical Factors Associated with Cessation of Growth Hormone Therapy in Patients with Severe Growth Hormone Deficiency - Real World Evidence
Nageswary Nadarajah, Emmanuel Ssemmondo, Shani Brooks, Remi Akinyombo, Kazeem Adeleke, Harshal Deshmukh, Thozhukat Sathyapalan
International Journal of Endocrinology and Metabolism.2024;[Epub] CrossRef
Clinical and genetic features of childhood-onset congenital combined pituitary hormone deficiency: a retrospective, single-center cohort study
Yoonha Lee, Young Ah Lee, Jung Min Ko, Choong Ho Shin, Yun Jeong Lee
Annals of Pediatric Endocrinology & Metabolism.2024; 29(6): 379. CrossRef
Relationship between the Stimulated Peak Growth Hormone Level and Metabolic Parameters in Children with Growth Hormone Deficiency
Seong Yong Lee
The Ewha Medical Journal.2023;[Epub] CrossRef
Dyslipidaemia and growth hormone deficiency – A comprehensive review
Matthias Hepprich, Fahim Ebrahimi, Emanuel Christ
Best Practice & Research Clinical Endocrinology & Metabolism.2023; 37(6): 101821. CrossRef

Review Article

Miscellanenous
Cushing Syndrome Associated Myopathy: It Is Time for a Change: Martin Reincke; Endocrinol Metab. 2021;36(3):564-571. Published online June 18, 2021; DOI: https://doi.org/10.3803/EnM.2021.1069

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Cushing syndrome is the result of excessive levels of glucocorticoids. Endogenous Cushing syndrome is rare with an incidence of two to three cases per million per year. Clinically, the presentation consists of a characteristic phenotype including skin symptoms and metabolic manifestations. A frequent co-morbidity with high impact on quality of life is Cushing syndrome associated myopathy. It characteristically affects the proximal myopathy, impairing stair climbing and straightening up. The pathophysiology is complex and involves protein degradation via the forkhead box O3 (FOXO3) pathway, intramuscular fat accumulation, and inactivity-associated muscle atrophy. Surgical remission of Cushing syndrome is the most important step for recovery of muscle function. Restoration depends on age, co-morbidities and postoperative insulin-like growth factor concentrations. At average, functionality remains impaired during the long-term compared to age and sex matched control persons. Growth hormone therapy in individuals with impaired growth hormone secretion could be an option but has not been proved in a randomized trial.

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Osteosarcopenic adiposity and its relation to cancer and chronic diseases: Implications for research to delineate mechanisms and improve clinical outcomes
Jasminka Z. Ilich, Biljana Pokimica, Danijela Ristić-Medić, Snjezana Petrović, Aleksandra Arsić, Nadja Vasiljević, Vesna Vučić, Owen J. Kelly
Ageing Research Reviews.2025; 103: 102601. CrossRef
Long-Term Consequences of Cushing Syndrome: A Systematic Literature Review
Soraya Puglisi, Anna Maria Elena Perini, Cristina Botto, Francesco Oliva, Massimo Terzolo
The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e901. CrossRef
Perioperative Management of an Unusual Case of Dual Etiology Myopathy Undergoing Surgery for an Adrenal Tumor
Himanshu Sekhar Satapathy, Sakshi Gera, Lalit Sehgal
Journal of Indian College of Anaesthesiologists.2024; 3(2): 86. CrossRef
The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
Diabetes & Metabolism Journal.2023; 47(2): 153. CrossRef
Intelligent Systems for Muscle Tracking: A Review on Sensor‐Algorithm Synergy
Arjun Putcha, Tien Nguyen, Regina Smith, Rachel Choffin, Wubin Bai
Advanced Intelligent Systems.2023;[Epub] CrossRef
Sarcopenia in youth
Han Na Jung, Chang Hee Jung, You-Cheol Hwang
Metabolism.2023; 144: 155557. CrossRef
Cushing Syndrome
Martin Reincke, Maria Fleseriu
JAMA.2023; 330(2): 170. CrossRef
Musculoskeletal complications of Cushing syndrome
Dorota Leszczyńska, Alicja Szatko, Lucyna Papierska, Wojciech Zgliczyński, Piotr Glinicki
Rheumatology.2023; 61(4): 271. CrossRef
Circulating myomiRNAs as biomarkers in patients with Cushing’s syndrome
C. Pivonello, R. Patalano, C. Simeoli, T. Montò, M. Negri, F. Amatrudo, N. Di Paola, A. Larocca, E. M. Crescenzo, R. Pirchio, D. Solari, C. de Angelis, R. S. Auriemma, L. M. Cavallo, A. Colao, R. Pivonello
Journal of Endocrinological Investigation.2023; 47(3): 655. CrossRef
Low-grade inflammation during the glucocorticoid withdrawal phase in patients with Cushing's syndrome
Frederick Vogel, Leah Braun, Stephanie Zopp, Elisabeth Nowak, Jochen Schreiner, Irina Benz, German Rubinstein, Heike Künzel, Katrin Ritzel, Matthias Kroiss, Jürgen Honegger, Felix Beuschlein, Katharina Schilbach, Daniel Teupser, Martin Bidlingmaier, Marti
European Journal of Endocrinology.2023; 188(4): 375. CrossRef
An odd case of immune-mediated necrotizing myopathy, complicated with sagittal, transverse and sigmoid sinus thrombosis
Andreea Trandafir, Violeta Claudia Bonjincă, Delia Tulba, Gelu Onose
Balneo and PRM Research Journal.2023; 14(Vol.14, no): 630. CrossRef
Morbidität und Mortalität beim Cushing-Syndrom
Frederick Vogel, Leah Braun, Martin Reincke
Der Internist.2022; 63(1): 34. CrossRef
Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside
Vittoria Favero, Arianna Cremaschi, Chiara Parazzoli, Alberto Falchetti, Agostino Gaudio, Luigi Gennari, Alfredo Scillitani, Fabio Vescini, Valentina Morelli, Carmen Aresta, Iacopo Chiodini
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Leah T. Braun, Frederick Vogel, Martin Reincke
Journal of Neuroendocrinology.2022;[Epub] CrossRef
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Elena Valassi
Journal of Neuroendocrinology.2022;[Epub] CrossRef
Pyruvate dehydrogenase kinase 4 promotes ubiquitin–proteasome system‐dependent muscle atrophy
Ibotombi Singh Sinam, Dipanjan Chanda, Themis Thoudam, Min‐Ji Kim, Byung‐Gyu Kim, Hyeon‐Ji Kang, Jung Yi Lee, Seung‐Hoon Baek, Shin‐Yoon Kim, Bum Jin Shim, Dongryeol Ryu, Jae‐Han Jeon, In‐Kyu Lee
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Consensus on diagnosis and management of Cushing's disease: a guideline update
Maria Fleseriu, Richard Auchus, Irina Bancos, Anat Ben-Shlomo, Jerome Bertherat, Nienke R Biermasz, Cesar L Boguszewski, Marcello D Bronstein, Michael Buchfelder, John D Carmichael, Felipe F Casanueva, Frederic Castinetti, Philippe Chanson, James Findling
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Original Article

Clinical Study
Associations of GNAS Mutations with Surgical Outcomes in Patients with Growth Hormone-Secreting Pituitary Adenoma: Hyein Jung, Kyungwon Kim, Daham Kim, Ju Hyung Moon, Eui Hyun Kim, Se Hoon Kim, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2021;36(2):342-350. Published online March 23, 2021; DOI: https://doi.org/10.3803/EnM.2020.875

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Background
The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics.
Methods
We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor.
Results
GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively).
Conclusion
GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

Citations

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Genetic diagnosis in acromegaly and gigantism: From research to clinical practice
Claudia Ramírez-Rentería, Laura C. Hernández-Ramírez
Best Practice & Research Clinical Endocrinology & Metabolism.2024; 38(3): 101892. CrossRef
Unlocking the Genetic Secrets of Acromegaly: Exploring the Role of Genetics in a Rare Disorder
Ioana Balinisteanu, Lavinia Caba, Andreea Florea, Roxana Popescu, Laura Florea, Maria-Christina Ungureanu, Letitia Leustean, Eusebiu Vlad Gorduza, Cristina Preda
Current Issues in Molecular Biology.2024; 46(8): 9093. CrossRef
Advancements in Molecular Diagnosis and Pharmacotherapeutic Strategies for Invasive Pituitary Adenomas
Dingkai Xu, Ling Wang, Maohua Zheng
Immunity, Inflammation and Disease.2024;[Epub] CrossRef
CD8/PD-L1 immunohistochemical reactivity and gene alterations in cutaneous squamous cell carcinoma
Haruto Nishida, Yoshihiko Kondo, Takahiro Kusaba, Kazuhiro Kawamura, Yuzo Oyama, Tsutomu Daa, Avaniyapuram Kannan Murugan
PLOS ONE.2023; 18(2): e0281647. CrossRef
Dynamic monitoring of circulating tumor DNA to analyze genetic characteristics and resistance profile of lorlatinib in ALK positive previously treated NSCLC
Xiya Ma, Kun Zhang, Jing Xu, Hongjun Gao, Shaoxing Yang, Haifeng Qin, Hong Wang, Fang Gao, Xiaoqing Liu
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Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine
Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee
Endocrinology and Metabolism.2023; 38(5): 463. CrossRef
Hotspots of Somatic Genetic Variation in Pituitary Neuroendocrine Tumors
Mariana Torres-Morán, Alexa L. Franco-Álvarez, Rosa G. Rebollar-Vega, Laura C. Hernández-Ramírez
Cancers.2023; 15(23): 5685. CrossRef

Brief Report

Hypothalamus and Pituitary gland
Reference Ranges of Serum Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3: Results from a Multicenter Study in Healthy Korean Adults: In-Kyung Jeong, Jong Kyu Byun, Junghyun Noh, Sang Wan Kim, Yoon-Sok Chung, Tae Sun Park, Sung-Woon Kim; Endocrinol Metab. 2020;35(4):954-959. Published online December 1, 2020; DOI: https://doi.org/10.3803/EnM.2020.785

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Insulin-like growth factor-I (IGF-I) plays a pivotal role in the diagnosis and treatment of growth hormone (GH) excess or deficiency. The GH study group of the Korean Endocrine Society aims to establish the Korean reference ranges of serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) and assess the relationship between IGF-I and IGFBP-3 and clinical parameters. Fasting serum was collected from healthy Korean adults at health promotion centers of five hospitals nationwide. Serum IGF-I and IGFBP-3 were measured via an immunoradiometric assay using a DSL kit (Diagnostic Systems Laboratories). Serum samples from 354 subjects (180 male, 174 female) were analyzed based on sex at 10-year intervals from 21 to 70 years. IGF-I levels were inversely correlated with age. After adjustment of age, the IGF-I/IGFBP-3 ratio was significantly negatively associated with blood pressure and free thyroxine and positively associated with weight, hemoglobin, creatinine, alanine transferase, fasting glucose, and thyroid stimulating hormone. Therefore, age- and sex-specific reference ranges of serum IGF-I and IGFBP-3 can be efficient in evaluating GH excess or deficiency in Korean population.

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Ji-Hee Sung, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
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Special Article

Miscellaneous
Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology: Jung Hee Kim, Hyun Wook Chae, Sang Ouk Chin, Cheol Ryong Ku, Kyeong Hye Park, Dong Jun Lim, Kwang Joon Kim, Jung Soo Lim, Gyuri Kim, Yun Mi Choi, Seong Hee Ahn, Min Ji Jeon, Yul Hwangbo, Ju Hee Lee, Bu Kyung Kim, Yong Jun Choi, Kyung Ae Lee, Seong-Su Moon, Hwa Young Ahn, Hoon Sung Choi, Sang Mo Hong, Dong Yeob Shin, Ji A Seo, Se Hwa Kim, Seungjoon Oh, Sung Hoon Yu, Byung Joon Kim, Choong Ho Shin, Sung-Woon Kim, Chong Hwa Kim, Eun Jig Lee; Endocrinol Metab. 2020;35(2):272-287. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.272

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Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

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Anastasia Ibba, Chiara Guzzetti, Lavinia Sanfilippo, Sandro Loche
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L‐DOPA Test in the Diagnosis of Childhood Short Stature: Evaluation of Growth Hormone Peaks Over Time
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Kaiyu Pan, Xiaoguang Jiang, Xiaohong Hu, Jianhua Zhan, Chengyue Zhang
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Nageswary Nadarajah, Emmanuel Ssemmondo, Shani Brooks, Remi Akinyombo, Kazeem Adeleke, Harshal Deshmukh, Thozhukat Sathyapalan
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Charlotte Steenblock, Stefan R. Bornstein
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Hyeon Jun Jung, Jeong Rye Kim, Jeesuk Yu
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Evaluation of Adult Height in Patients with Non-Permanent Idiopathic GH Deficiency
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Review Article

Hypothalamus and Pituitary gland
Precision Therapy in Acromegaly Caused by Pituitary Tumors: How Close Is It to Reality?: Cheol Ryong Ku, Vladimir Melnikov, Zhaoyun Zhang, Eun Jig Lee; Endocrinol Metab. 2020;35(2):206-216. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.206

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Acromegaly presents with an enigmatic range of symptoms and comorbidities caused by chronic and progressive growth hormone elevations, commonly due to endocrinologic hypersecretion from a pituitary gland tumor. Comprehensive national acromegaly databases have been appearing over the years, allowing for international comparisons of data, although still presenting varying prevalence and incidence rates. Lack of large-scale analysis in geographical and ethnic differences in clinical presentation and management requires further research. Assessment of current and novel predictors of responsiveness to distinct therapy can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and reduction of increased morbidity and mortality associated with acromegaly. This review compares current data from epidemiological studies and assesses the present-day application of prognostic factors in medical practice, the reality of precision therapy, as well as its future prospects in acromegaly, with a special focus on its relevance to the South Korean population.

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Predictors of morphofunctional features of somatotrophic tumors and of the effectiveness of treatment with first-generation somatostatin receptor ligands
E. V. Pronin, V. S. Pronin, M. B. Antsiferov, A. V. Petryaykin, T. M. Alexeeva, A. M. Lapshina, L. S. Urusova, A. N. Khoruzhaya, S. M. Tamaeva
Meditsinskiy sovet = Medical Council.2024; (6): 98. CrossRef
Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma
Min-Ho Lee, Jae Won Hong, Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee
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Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine
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Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study
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European Journal of Endocrinology.2023; 189(3): 363. CrossRef
The Future of Somatostatin Receptor Ligands in Acromegaly
Monica R Gadelha, Luiz Eduardo Wildemberg, Leandro Kasuki
The Journal of Clinical Endocrinology & Metabolism.2022; 107(2): 297. CrossRef
Innovative therapeutics in acromegaly
Leandro Kasuki, Mônica R. Gadelha
Best Practice & Research Clinical Endocrinology & Metabolism.2022; 36(6): 101679. CrossRef
Risk of Neurodegenerative Diseases in Patients With Acromegaly
Sangmo Hong, Kyungdo Han, Kyung-Soo Kim, Cheol-Young Park
Neurology.2022;[Epub] CrossRef
Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands
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The Journal of Clinical Endocrinology & Metabolism.2021; 106(7): 2047. CrossRef
Skin anomalies in acromegalic patients (Review of the practical aspects)
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Experimental and Therapeutic Medicine.2021;[Epub] CrossRef

Original Articles

Endocrine Research
Therapeutic Effect of a Novel Chimeric Molecule Targeting Both Somatostatin and Dopamine Receptors on Growth Hormone-Secreting Pituitary Adenomas: Jean Kim, Ju Hun Oh, Heather Harlem, Michael D. Culler, Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2020;35(1):177-187. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.177

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Background

Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs with improved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist.

Methods

The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigated with MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration of BIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changes in IGF-1 levels before and after treatment was further investigated.

Results

In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065 using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantly following treatment with BIM23B065 for 4 weeks.

Conclusion

The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeutic agent for acromegaly.

Citations

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Pituitary Tumorigenesis—Implications for Management
Rodanthi Vamvoukaki, Maria Chrysoulaki, Grigoria Betsi, Paraskevi Xekouki
Medicina.2023; 59(4): 812. CrossRef
Current and Emerging Medical Therapies in Pituitary Tumors
Nicolas Sahakian, Frédéric Castinetti, Thierry Brue, Thomas Cuny
Journal of Clinical Medicine.2022; 11(4): 955. CrossRef
Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells
Thomas Cuny, Thomas Graillon, Célines Defilles, Rakesh Datta, Shengwen Zhang, Dominique Figarella-Branger, Henry Dufour, Grégory Mougel, Thierry Brue, Tanya Landsman, Heather A. Halem, Michael D. Culler, Anne Barlier, Alexandru Saveanu
Pituitary.2021; 24(3): 351. CrossRef
Efficacy of a Novel Second-Generation Somatostatin-Dopamine Chimera (TBR-065) in Human Medullary Thyroid Cancer: A Preclinical Study
Alessandra Dicitore, Maria Celeste Cantone, Germano Gaudenzi, Davide Saronni, Silvia Carra, Maria Orietta Borghi, Manuela Albertelli, Diego Ferone, Leo J. Hofland, Luca Persani, Giovanni Vitale
Neuroendocrinology.2021; 111(10): 937. CrossRef
Emerging drugs for the treatment of acromegaly
Claudia Campana, Giuliana Corica, Federica Nista, Francesco Cocchiara, Giulia Graziani, Keyvan Khorrami, Marta Franco, Mara Boschetti, Diego Ferone, Federico Gatto
Expert Opinion on Emerging Drugs.2020; 25(4): 409. CrossRef

Clinical Effects of E. coli Derived Recombinant Human Growth Hormone (DA - 3001) in Patients with Growth Hormone Deficiency.: Sei Won Yang, Jeh Hoon Shin, Duk Hi Kim, Byung Churl Lee, Hyung Ro Moon; J Korean Endocr Soc. 1995;10(4):377-385. Published online November 7, 2019

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Abstract PDF: Recently, methionyl-hGH was produced in the E. coil K-12, W3110 by recombinant DNA technology in Korea. In this paper, the clinical efficacy and immunogenicity of this GH were studied in 43 patients with growth hormone deficency.The subjects of this study were aged 4.3-18.5 years and each patient received GH 0.5-0.71U/kg week subcutaneously, 6-7 times a week for 1 year. During treatment, height, body weight and bone age were checked. Blood count, urinalysis, blood chemistry and thyroid hormonal concentrations were checked before and every 3 months. The measurement of IGF-1 was performed and assay of antibody against hGH was performed before and every 6 months.The height velocities significantly increased from 3.7+-3.0 cm/year to 11.0+-4.2 cm/year and 9.9+-3.2 cm/year at 6 and 12 months after GH therapy, respectively. The Height SDS were significantly improved after GH therapy with increasing ratio of bone age to chronological age from 0.60+-0.19 at pretreatment to 0.68+-0.16 at 6 month, 0.69+-0.16 at 12 month of therapy. The plasma IGF-1 levels significantly increased during treatment. Three out of 35 patients(8.3%) showed antibody against hGH after 1 year of treatment. Thoughout study, we could not observe any remarkable side effect with GH treatment.These results indicate that this E. coli derived methionyl recombinant growth hormone is effective in improving the index of linear growth in the children with growth hormone deficiency without significant side effect.

Correlation between Urinary Growth Hormone Level and Peak Serum Growth Hormone Level in Growth Hormone Provocation Test Using Insulin and L - dopa.: Woo Yeong Chung, Byung Kiu Park, Chul Ho Kim; J Korean Endocr Soc. 1995;10(4):370-376. Published online November 7, 2019

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Abstract PDF: To investigate the correlation between urinary growth hormone(GH) level and peak serum GH level, urinary GH value measured by overnight collection of urine for 10 hours and serum GH value in response to GH provocation test using insulin and L-dopa were measured in 9 cases of GH complete deficiency(GCD), 19 cases of GH partial deficiency(GPD) and 40 cases of GH normal short stature(GHN). Urinary GH values were measured by the EIA method using PICOIA HGH plate(Joo Woo Pharmaceutical Co., Japan). Urinary GH was expressed in terms of nanograms per gm creatinine(ng/gCr). Serum GH was measured by immunoradiometric assay using "Daiichi kit"(Je Il Pharmaceutical Co., Japan). Wilcoxon ranked sum test and student's t-test were used to assess the significance of differences between the groups of the patients. The correlation between urinary GH level and peak serum GH level was assessed by the parametric Pearson correlation test. The correlation between peak serum GH level in GH provocation test using insulin and urinary GH level measured by overnight 10 hours collection method showed statistically significant results in all the patients(Y=0.464072X +9.208044, r=0.48987, p=0.0001) and in the GH deficiency groups(GCD+GPD) (Y=0.924659X +9.2385509, r=0.80437, p=0.0001). In case of L-dopa stimulation test, urinary GH values were also positively correlated with peak serum GH level when all the patients were participated(Y=0.572988X +8.312993, r=0.58212, p=0.0001). In contrast, no correlation was found when patients were confined to GH deficiency group(GCD+GPD)(Y=0.127712X +8.3129939, r=0.08044, p=0.6841).

Changes of Bone Turnover Markers after Treatment with Growth Hormone Therapy in Children with Growth Retardation.: In Myung Yang, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Ki Oak han, Duk Yoon Kim, Hyung In Yang; J Korean Endocr Soc. 1994;9(4):344-349. Published online November 6, 2019

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Abstract PDF: The effects of growth hormone(GH) deficiency and recombinant human GH replacement(0.5IU/kg per week) on bone mineral metabolism in 21GH-deficiency children were studied. All children had significantly reduction of bone density(Z score;-1.4+-0.71). After 1 month of therapy, the levels of serum insulin-like growth factor 1(IGF-1), osteocalcin(OC) and carboxyterminal propeptede of type 1 procollagen(PICP) were significantly elevated. But IGFBP-3 were not shown to change significantly. The changes in serum levels of PICP during the first month of recombinant human GH treatment were positively related to growth velocity, whereas the changes in IGF-1 and OC during the first month of therapy were not. We conclude that the recombinant human GH treatment caused significant modifications of mineral metablism and that the measurement of the changes of biochemical markers of bone metablism espacially PICP may be a useful tool in prediction improved growth velocity during long term GH replacement therpy.

In Situ Hybridization Analysis of Human Growth Hormone and Prolactin Secreting Pitultary Adenomas.: Jae Wha Jo, Eun Jig Lee, Moon Suk Nam, Kyung Rae Kim, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Tae Seung Kim, Sun Ho Kim, Joong Uhn Choi, Kyu Chang Lee, Hyun Joo Jung, Sang Seop Chung; J Korean Endocr Soc. 1994;9(2):82-92. Published online November 6, 2019

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Abstract PDF: A non-isotopic in situ hybridization method with biotin-labelled oligonucleotide probes was used to examine growth hormone(GH) and prolactin(PRL) gene expression in 32 patients with pituitary adenomas; 13 were prolactinomas, 8 GH secreting adenomas, and 11 mixed GH and PRL secreting adenomas.Positive immunostaining for GH was found in all patients with GH secreting adenomas, and mixed GH and PRL secreting adenomas. Positive immunostaining for PRL was found in all patients with prolactinomas and 9(81.8%) of 11 mixed GH and PRL secreting adenomas, 5(62.5%) of 8 GH secreting adenomas. Immunohistochemistry revealed that 13 were lactotrope adenomas, 5 somatotrope adenomas, and 14 GH and PRL cell adenomas.In situ hybridization revealed that GH mRNA expression was found in all the patients with somatotrope adenomas and GH and PRL cell adenomas, and 6(46.1%) of 13 lactotrope adenomas. PRL mRNA expression was 100% in lactotrope and GH and PRL cell adenomas, and 4(80.0%) of 5 somatotrope adenomas.The patients with a clinical diagnosis of acromegaly had detectable PRL mRNA in their neoplasm and it is suggested that the PRL cells in the adenomas did not result from dedifferentiation, but from the neoplastic stimulus for some mixed tumors probably occurred in cells previously committed to produce PRL and GH. In lactotrope adenomas, the PRL cells of the patients without expression of GH mRNA may be arised from cells programmed to secrete PRL or precussor PRL cells rather than from mixed GH-PRL cells. The finding that some patients produced mRNA detectable by in situ hybridization, but no hormone detectable by immunohistochemistry within tumor was suggested of a silent adenoma.These observations indicated that in situ hybridization studies may improve the classification of pituitary adenomas and may provide a precise knowledge of the biology of these neoplasms.

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