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Original Article
Hypothalamus and pituitary gland
Obstructive Sleep Apnea Screening and Effects of Surgery in Acromegaly: A Prospective Study
Jaeyoung Cho, Jung Hee Kim, Yong Hwy Kim, Jinwoo Lee
Endocrinol Metab. 2024;39(4):641-652.   Published online June 26, 2024
DOI: https://doi.org/10.3803/EnM.2024.1933
  • 1,545 View
  • 57 Download
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To identify a screening tool for obstructive sleep apnea (OSA) and evaluate the effects of endoscopic transsphenoidal surgery on improving OSA in patients with acromegaly.
Methods
We prospectively enrolled adults with acromegaly scheduled for endoscopic transsphenoidal surgery. All measurements were conducted when participants were admitted for a baseline work-up for acromegaly before surgery and surveillance approximately 3 to 6 months after surgery. Respiratory event index (REI) was used as a surrogate for apnea-hypopnea index (Trial Registration: NCT03526016).
Results
Of the 35 patients with acromegaly (median age, 47 years; 40% men; median body mass index, 24.4 kg/m2), 24 (68.6%) had OSA (REI ≥5/hour), 15 (42.9%) had moderate-to-severe OSA (REI ≥15/hour). At baseline, serum insulin-like growth factor 1 (IGF-1) levels were positively correlated with the REI (ρ=0.53, P=0.001). The sensitivity and negative predictive value of a Snoring, Tiredness, Observed apnea, high blood Pressure-Body mass index, age, Neck circumference, and Gender (STOP-Bang) score ≥ 3 were 93.3% and 87.5%, respectively, detecting moderate-to-severe OSA. Biochemical acromegaly remission was achieved in 32 (91.4%) patients. The median difference in the REI was –9.5/hour (95% confidence interval, –13.3 to –5.3). Half of the 24 patients diagnosed with OSA preoperatively had REI <5/hour postoperatively. In a linear mixed-effects model, changes in the REI across surgery were related to changes in IGF-1 levels.
Conclusion
The STOP-Bang questionnaire is a reliable tool for OSA among patients with acromegaly. Improvement in OSA severity after surgery is related to decreased IGF-1 levels.

Citations

Citations to this article as recorded by  
  • How Different Treatments for Acromegaly Modulate Sleep Quality: A Psychometric Study
    Gaspare Alfì, Danilo Menicucci, Dalì Antonia Ciampa, Vito Di Giura, Giulia Marconcini, Claudio Urbani, Fausto Bogazzi, Angelo Gemignani
    Endocrines.2024; 5(3): 408.     CrossRef
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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
  • 37,346 View
  • 662 Download
  • 6 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • 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
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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
  • 4,290 View
  • 236 Download
  • 13 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • 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
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Original Article
Calcium & bone metabolism
Big Data Articles (National Health Insurance Service Database)
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea
Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku
Endocrinol Metab. 2023;38(6):690-700.   Published online October 30, 2023
DOI: https://doi.org/10.3803/EnM.2023.1782
  • 2,798 View
  • 123 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Acromegaly leads to various skeletal complications, and fragility fractures are emerging as a new concern in patients with acromegaly. Therefore, this study investigated the risk of fractures in Korean patients with acromegaly.
Methods
We used the Korean nationwide claims database from 2009 to 2019. A total of 931 patients with acromegaly who had never used an osteoporosis drug before and were treated with surgery alone were selected as study participants, and a 1:29 ratio of 26,999 age- and sex-matched osteoporosis drug-naïve controls without acromegaly were randomly selected from the database.
Results
The mean age was 46.2 years, and 50.0% were male. During a median follow-up of 54.1 months, there was no difference in the risks of all, vertebral, and non-vertebral fractures between the acromegaly and control groups. However, hip fracture risk was significantly higher (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.32 to 5.65), and non-hip and non-vertebral fractures risk was significantly lower (HR, 0.40; 95% CI, 0.17 to 0.98) in patients with acromegaly than in controls; these results remained robust even after adjustment for socioeconomic status and baseline comorbidities. Age, type 2 diabetes mellitus, cardio-cerebrovascular disease, fracture history, recent use of acid-suppressant medication, psychotropic medication, and opioids were risk factors for all fractures in patients with acromegaly (all P<0.05).
Conclusion
Compared with controls, patients surgically treated for acromegaly had a higher risk of hip fractures. The risk factors for fracture in patients with acromegaly were consistent with widely accepted risk factors in the general population.

Citations

Citations to this article as recorded by  
  • 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
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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
  • 3,354 View
  • 180 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • “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
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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
  • 5,553 View
  • 157 Download
  • 9 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   ePub   
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

Citations to this article as recorded by  
  • 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
    Thoracic Cancer.2023; 14(20): 1980.     CrossRef
  • 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
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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
  • 8,004 View
  • 270 Download
  • 8 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Biomarkers of response to treatment in acromegaly
    Leandro Kasuki, Elisa Lamback, Ximene Antunes, Mônica R. Gadelha
    Expert Review of Endocrinology & Metabolism.2024; 19(1): 71.     CrossRef
  • 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
    Endocrinology and Metabolism.2024; 39(6): 819.     CrossRef
  • 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
  • Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study
    Shinje Moon, Sangmo Hong, Kyungdo Han, Cheol-Young Park
    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
    Luiz Eduardo Wildemberg, Aline Helen da Silva Camacho, Renan Lyra Miranda, Paula C L Elias, Nina R de Castro Musolino, Debora Nazato, Raquel Jallad, Martha K P Huayllas, Jose Italo S Mota, Tobias Almeida, Evandro Portes, Antonio Ribeiro-Oliveira, Lucio Vi
    The Journal of Clinical Endocrinology & Metabolism.2021; 106(7): 2047.     CrossRef
  • Skin anomalies in acromegalic patients (Review of the practical aspects)
    Florica Sandru, Adelina Popa, Dan Paduraru, Alexandru Filipescu, Mara Carsote, Adina Ghemigian
    Experimental and Therapeutic Medicine.2021;[Epub]     CrossRef
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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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  • 4 Web of Science
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AbstractAbstract PDFPubReader   ePub   
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

Citations to this article as recorded by  
  • 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
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A Case of Thyroid Papillary Cancer Derived from Diffuse Goiter in a Patients with Acromegaly.
Dong Hee Kim, Jick Hwa Nam, Byoung Ho Sin, Ye Kyung Seo, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim, Young Ha Lee, In Su Seo
J Korean Endocr Soc. 1996;11(3):311-317.   Published online November 7, 2019
  • 1,291 View
  • 21 Download
AbstractAbstract PDF
Patients with acromegaly have a reduced life expectancy rnainly due to cardiovascular, respiratory or cerebrovascular diseas-. Malignancy also seems to occur with greater than the expected incidence. In particular, the published retrospective or prospective studies have suggested a strong association of colonic neoplasia with acromegaly. But, there were a few reports of thyroid cancer in acrornegaly. We report a case of thyroid papillary cancer derived from diffuse goiter in acromegaly, sugge- sting the possible carcinogenic role of growth hormone.
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Relationship between Blood Pressure and Insulin Level or Red Cell Membrane Na+ Transport in Acromegaly.
Seong Yeon Kim, Hyun Kyu Kim, Kyung Soo Park, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh
J Korean Endocr Soc. 1995;10(1):35-44.   Published online November 6, 2019
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AbstractAbstract PDF
To test the hypothesis that hyperinsulinemia and/or abnormalities of red cell membrane Na^+ transport are concerned in the pathogenesis of hypertension, we investigated the relationship between blood pressure, insulin level and red cell membrane Na^+ transport in patients with acromegaly which is frequently associated with hypertension, hyperinsulinemia and abnormalities of red cell membrane Na^+ transport.The results were as follows;1) BMI and both systolic and diastolic blood pressure were significantly higher in patients with acromegaly than in control subjects.2) Fasting glucose and insulin levels were higher, and both serum glucose and insulin responses after a 75g glucose load were significantly increased in patients with acromegaly as compared with control subjects.3) Vmax of Na^+-Li^+ countertransport were significantly higher in patients with acromegaly than in control subjects while red cell Na^+ concentration and Vmax of Na^+, K^+ ATPase were similar in the two groups.4) In multiple stepwise regression analysis, age was directly correlated with both systolic and diastolic blood pressure in acromegaly. On the other hand both insulin level and red cell membrane Na^+ transport showed little correlation with either systolic or diastolic pressure. 5) Prevalence of hypertension in acromegaly was 39%(9 out of 23) and only age except for blood pressure was significantly higher in hypertensive acromegalic patients than in normotensive acromegalic patients while GH level, insulin levels and red cell membrane Na^+ transport were similar in the two groupsThese results suggest that hyperinsulinemia or abnormalities of red cell membrane Na^+ transport are not causally related to hypertension in patients with acromegaly.
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Special Article
Hypothalamus and Pituitary gland
Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong Jun Lim, Dong Yeob Shin, Se Hwa Kim, Min Jeong Kwon, Ha Young Kim, Jin Hwa Kim, Dong Sun Kim, Chong Hwa Kim
Endocrinol Metab. 2019;34(1):53-62.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.53
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AbstractAbstract PDFPubReader   ePub   

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

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Review Article
Recent Progress in the Medical Therapy of Pituitary Tumors
Fabienne Langlois, Shirley McCartney, Maria Fleseriu
Endocrinol Metab. 2017;32(2):162-170.   Published online May 19, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.2.162
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AbstractAbstract PDFPubReader   ePub   

Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.

Citations

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    Kyungwon Kim, Cheol Ryong Ku, Eun Jig Lee
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    Aging.2022; 14(15): 6066.     CrossRef
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    Tuo Wang, Ping Mao, Yan Zhang, Bo Cui, Mao-De Wang, Ya Li, Ke Gao
    Anti-Cancer Drugs.2022; 33(10): 1058.     CrossRef
  • Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas
    Carolina Carrillo-Najar, Daniel Rembao-Bojórquez, Martha L. Tena-Suck, Sergio Zavala-Vega, Noemí Gelista-Herrera, Miguel A. Ramos-Peek, Juan L. Gómez-Amador, Febe Cazares-Raga, Fidel de la Cruz Hernández-Hernández, Alma Ortiz-Plata
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Case Reports
Adrenal gland
Multiple Myeloma in a Patient with Acromegaly
Yu Mi Kang, Jong Han Choi, Min Jung Lee, Ari Ahn, Chan-Jeoung Park, Kiju Chang, Seyoung Seo, Sun In Hong, Min-Seon Kim
Endocrinol Metab. 2015;30(1):110-115.   Published online March 27, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.1.110
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AbstractAbstract PDFPubReader   

Acromegaly is a slowly progressing condition resulting from excess growth hormone (GH), generally caused by a GH-secreting pituitary adenoma. Cancer is the third most common cause of mortality in patients with acromegaly, and insulin-like growth factor 1 (IGF-1) is known to influence tumor formation by increasing cell proliferation and inhibiting apoptosis. Multiple myeloma (MM) is a plasma cell neoplasm, and previous studies have suggested the possible role of IGF-1 in its development of MM. However, no cases of acromegaly accompanied with MM have been reported in Asia to date. We here report the case of a 58-year-old woman with acromegaly accompanied with MM who presented with longstanding acromegalic manifestations resulting from a GH-secreting pituitary adenoma and also exhibited anemia, a reversed albumin/globulin ratio, and plasmacytosis on bone marrow examination. Because IGF-1 has been suggested to play an important role in the development and progression of MM, the patient promptly underwent surgical removal of the pituitary adenoma via a transsphenoidal approach. Since there is currently no consensus on therapeutic guidelines and suggested prognosis for MM with acromegaly, long-term follow-up of such cases is needed.

Citations

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  • Co-Occurrence of Acromegaly and Hematological Disorders: A Myth or Common Pathogenic Mechanism
    Prakamya Gupta, Pinaki Dutta
    Integrative Medicine International.2017; 4(1-2): 94.     CrossRef
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Adrenal gland
Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor
Sang Ouk Chin, Jin-Kyung Hwang, Sang Youl Rhee, Suk Chon, Seungjoon Oh, Misu Lee, Natalia S. Pellegata, Sung-Woon Kim
Endocrinol Metab. 2015;30(3):389-394.   Published online January 5, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.389
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AbstractAbstract PDFPubReader   

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor.

Citations

Citations to this article as recorded by  
  • Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study
    Caiyan Mo, Han Chen, Jian Xu, Ying Guo, Yao Wang, Zheng Li, Tao Tong, Songbai Gui, Liyong Zhong
    Endocrine Practice.2024; 30(5): 441.     CrossRef
  • Growth Hormone Excess: Implications and Management
    Suneela Dhaneshwar, Shrishti Shandily, Vatsalya Tiwari
    Endocrine, Metabolic & Immune Disorders - Drug Targets.2023; 23(6): 748.     CrossRef
  • Pleiomorphism plurihormonal Pit-1-positive macroadenoma with central hyperthyroidism: a rare case report and literature review
    Guiliang Peng, Chuanhong Guo, Yangfan Lv, Dandan Li, Ling Zhou, Rufei Shen, Yong Chen, Xin Zheng, Zheng Sun, Hongting Zheng, Min Long
    BMC Endocrine Disorders.2022;[Epub]     CrossRef
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Original Article
Adrenal gland
Association between the Growth Hormone Receptor Exon 3 Polymorphism and Metabolic Factors in Korean Patients with Acromegaly
Hye Yoon Park, In Ryang Hwang, Jung Bum Seo, Su Won Kim, Hyun Ae Seo, In Kyu Lee, Jung Guk Kim
Endocrinol Metab. 2015;30(3):312-317.   Published online January 5, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.312
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AbstractAbstract PDFPubReader   
Background

This study investigated the association between the frequency of growth hormone receptor (GHR) exon 3 polymorphism (exon 3 deletion; d3-GHR) and metabolic factors in patients with acromegaly in Korea.

Methods

DNA was extracted from the peripheral blood of 30 unrelated patients with acromegaly. GHR genotypes were evaluated by polymerase chain reaction and correlated with demographic data and laboratory parameters.

Results

No patient had the d3/d3 genotype, while four (13.3%) had the d3/fl genotype, and 26 (86.7%) had the fl/fl genotype. Body mass index (BMI) in patients with the d3/fl genotype was significantly higher than in those with the fl/fl genotype (P=0.001). Age, gender, blood pressure, insulin-like growth factor-1, growth hormone, fasting plasma glucose, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol levels showed no significant differences between the two genotypes.

Conclusion

The d3-GHR polymorphism may be associated with high BMI but not with other demographic characteristics or laboratory parameters.

Citations

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  • The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function
    Ghadeer Falah, Lital Sharvit, Gil Atzmon
    International Journal of Molecular Sciences.2023; 24(18): 13908.     CrossRef
  • Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents
    Xiaotian Chen, Chunlan Liu, Song Yang, Yaming Yang, Yanchun Chen, Xianghai Zhao, Weiguang Zhu, Qihui Zhao, Chuan Ni, Xiangyuan Huang, Weili Yan, Chong Shen, Harvest F. Gu
    Frontiers in Pediatrics.2022;[Epub]     CrossRef
  • Exon 3-deleted growth hormone receptor isoform is not related to worse bone mineral density or microarchitecture or to increased fracture risk in acromegaly
    J. Pontes, M. Madeira, C. H. A. Lima, L. L. Ogino, F. de Paula Paranhos Neto, L. M. C. de Mendonça, M. L. F. Farias, L. Kasuki, M. R. Gadelha
    Journal of Endocrinological Investigation.2020; 43(2): 163.     CrossRef
  • MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?
    Reetobrata Basu, Yanrong Qian, John J Kopchick
    European Journal of Endocrinology.2018; 178(5): R155.     CrossRef
  • MECHANISMS IN ENDOCRINOLOGY: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism
    Cesar L Boguszewski, Edna J L Barbosa, Per-Arne Svensson, Gudmundur Johannsson, Camilla A M Glad
    European Journal of Endocrinology.2017; 177(6): R309.     CrossRef
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