Endocrinology and Metabolism

Ju Hyung Moon

3 Articles

Mineral, Bone & Muscle 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

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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

Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data
Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2025; 40(1): 1. CrossRef
Musculoskeletal disease in acromegaly—a population-based registry study
Christian Rosendal, Mai Christiansen Arlien-Søborg, Eigil Husted Nielsen, Claus Larsen Feltoft, Åse Krogh Rasmussen, Marianne Skovsager Andersen, Jens Otto Lunde Jørgensen, Jakob Dal
European Journal of Endocrinology.2025; 192(3): 308. 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

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

Citations to this article as recorded by

Contract to kill: GNAS mutation
Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy
Molecular Cancer.2025;[Epub] CrossRef
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
GNAS mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma
CHAO TANG, CHUNYU ZHONG, JUNHAO ZHU, FENG YUAN, JIN YANG, YONG XU, CHIYUAN MA
Oncology Research.2024; 32(6): 1079. 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

⁶⁸Ga-DOTATOC PET/CT in the Localization of Pituitary Tumors in Cushing’s Disease: Kyungwon Kim, Dongwoo Kim, Min-Ho Lee, Yae Won Park, Sung Soo Ahn, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Cheol Ryong Ku, Eun Jig Lee; Received November 20, 2024 Accepted January 21, 2025 Published online March 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2249 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
This study aimed to determine the value of ⁶⁸Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) in localizing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas.
Methods
In this retrospective cohort study, we enrolled 30 patients with Cushing’s disease and positive ACTH immunoreactivity. All patients underwent ⁶⁸Ga-DOTATOC PET/CT and pituitary magnetic resonance imaging (MRI) before transsphenoidal adenomectomy.
Results
Twenty-five patients showed ⁶⁸Ga-DOTATOC uptake in their pituitary glands on PET/CT. Median age, pre-operative ACTH levels, pre-operative cortisol, and tumor size on MRI were comparable irrespective of DOTATOC uptake. ⁶⁸Ga-DOTATOC PET/CT showed a 77% success rate for localizing adenomas, which was not statistically different from that of MRI. The ACTH level in the successful localization group was significantly higher than that in the failed group (84.41 pg/mL vs. 37.26 pg/mL, P=0.001). The ACTH level was statistically significant predictor of successful localization using ⁶⁸Ga-DOTATOC PET/CT (P=0.013). The area under the curve was 0.932 with a cutoff of 53.86 pg/mL for ACTH levels to determine successful localization. Pre-operative ACTH levels above 53.86 pg/mL showed the best diagnostic accuracy in predicting the success of localizing adenomas (sensitivity, 91.3%; specificity, 85.7%). Mean and maximum standardized uptake value of adenoma negatively correlated to pre-operative ACTH level.
Conclusion
Plasma ACTH level is a favorable predictor for the successful localization and negative correlation with ⁶⁸Ga-DOTATOC uptake of corticotroph adenomas in ⁶⁸Ga-DOTATOC PET/CT. ⁶⁸Ga-DOTATOC PET/CT did not improve tumor localization for Cushing’s disease compared with MRI alone.

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