Endocrinology and Metabolism

Original Articles

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

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; : 101892. 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
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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

Clinical Study
Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer: Eun Jeong Ban, Daham Kim, Jin Kyong Kim, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Kunhong Kim; Endocrinol Metab. 2021;36(1):96-105. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.819

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Abstract PDF Supplementary Material PubReader ePub

Background
Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV^600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker.
Methods
LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV^600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results.
Results
LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV^600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV^600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages.
Conclusion
LDHA overexpression is associated with the BRAFV^600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.

Citations

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Nature Communications.2024;[Epub] CrossRef
Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors
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Cancer Medicine.2023; 12(8): 9384. CrossRef
LncRNA GLTC targets LDHA for succinylation and enzymatic activity to promote progression and radioiodine resistance in papillary thyroid cancer
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Cell Death & Differentiation.2023; 30(6): 1517. CrossRef
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Guochao Ye, Xiaomei Zhang, Mansheng Li, Zixiang Lin, Yongcan Xu, Haoru Dong, Jie Zhou, Jiaqi Zhang, Sheng Wang, Yunping Zhu, Xiaobo Yu, Xu Qian
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Targeting metabolism by B-raf inhibitors and diclofenac restrains the viability of BRAF-mutated thyroid carcinomas with Hif-1α-mediated glycolytic phenotype
Marianna Aprile, Simona Cataldi, Caterina Perfetto, Antonio Federico, Alfredo Ciccodicola, Valerio Costa
British Journal of Cancer.2023; 129(2): 249. CrossRef
circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
Hongguo Xie, Xiaopeng Lu
Open Medicine.2023;[Epub] CrossRef
The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer
Sai-li Duan, Min Wu, Zhe-Jia Zhang, Shi Chang
Journal of Translational Medicine.2023;[Epub] CrossRef
CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma
Hui-feng Wu, Hao Liu, Zhe-wei Zhang, Ji-min Chen
European Journal of Medical Research.2023;[Epub] CrossRef
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Jaime Eduardo Pachón Suárez, Marcela C. Salazar, Victor Z. Rizo
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Development of Metabolic Synthetic Lethality and Its Implications for Thyroid Cancer
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Drug delivery for metabolism targeted cancer immunotherapy
Taravat Khodaei, Sahil Inamdar, Abhirami P. Suresh, Abhinav P. Acharya
Advanced Drug Delivery Reviews.2022; 184: 114242. CrossRef
Sulfur quantum dot based fluorescence assay for lactate dehydrogenase activity detection
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STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis
Nan Huo, Rui Cong, Zhi-jia Sun, Wen-chao Li, Xiang Zhu, Chun-yuan Xue, Zhao Chen, Lu-yuan Ma, Zhong Chu, Yu-chen Han, Xiao-feng Kang, Song-hao Jia, Nan Du, Lei Kang, Xiao-jie Xu
Cell Death & Disease.2021;[Epub] CrossRef

Case Report

1-34 PTH Could Reverse Impaired Bone Mineralization Induced By the Overdose of Bisphosphonate.: Kyeong Hye Park, Kwang Joon Kim, Han Seok Choi, Kyoung Min Kim, Eun Young Lee, Seonhui Han, Hyun Sil Kim, Daham Kim, Hannah Seok, Eun Yeong Choe, Yumie Rhee, Sung Kil Lim; Endocrinol Metab. 2012;27(3):247-250. Published online September 19, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.3.247

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Abstract PDF: Bisphosphonates are the mainstay of osteoporosis treatment. Despite the fact that bisphosphonates have a relatively good safety record and are tolerated well by the majority of patients, serious adverse events have been associated with their use. A 41-year-old man had been diagnosed with osteoporosis and had taken etidronate 200 mg/day daily for 2 years due to the judgmental error. He was referred for the management of refractory bone pain and generalized muscle ache. Serum calcium, phosphate, 25-hydroxy-vitamin D (25(OH)D), and immunoreactive parathyroid hormone (iPTH) were within normal range. Plain X-ray showed multiple fractures. Whole body bone scan confirmed multiple sites of increased bone uptakes. Tetracycline-labeled bone biopsy showed typical findings of osteomalacia. He was diagnosed with iatrogenic, etidronate-induced osteomalacia. The patient received daily parathyroid hormone (PTH) injection for 18 months. PTH effectively reverses impaired bone mineralization caused by etidronate misuse. Currently, he is doing well without bone pain. Bone mineral density significantly increased, and the increased bone uptake was almost normalized after 18 months. This case seems to suggest that human PTH (1-34) therapy, possibly in association with calcium and vitamin D, is associated with important clinical improvements in patients with impaired bone mineralization due to the side effect of bisphosphonate.

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