Endocrinology and Metabolism

Special Articles

Miscellaneous
Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society: Hyemi Kwon, Eun Roh, Chang Ho Ahn, Hee Kyung Kim, Cheol Ryong Ku, Kyong Yeun Jung, Ju Hee Lee, Eun Heui Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Jun Sung Moon, Jin Hwa Kim, Mi-kyung Kim, The Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2022;37(6):839-850. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.1627

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Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

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Pembrolizumab plus lenvatinib for radically unresectable or metastatic renal cell carcinoma in the Japanese population
Ryo Fujiwara, Takeshi yuasa, kenichi kobayashi, tetsuya yoshida, susumu kageyama
Expert Review of Anticancer Therapy.2023; 23(5): 461. CrossRef

Miscellaneous
COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society: Cheol Ryong Ku, Kyong Yeun Jung, Chang Ho Ahn, Jun Sung Moon, Ju Hee Lee, Eun Heui Kim, Hyemi Kwon, Hee Kyung Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Eun Roh, Jin Hwa Kim, Mi-kyung Kim, the Committee of Clinical Practice Guideline of the Korean Endocrine Society; Endocrinol Metab. 2021;36(4):757-765. Published online August 17, 2021; DOI: https://doi.org/10.3803/EnM.2021.404

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Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

Citations

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Adult-Onset Type 1 Diabetes Development Following COVID-19 mRNA Vaccination
Hyeyeon Moon, Sunghwan Suh, Mi Kyoung Park
Journal of Korean Medical Science.2023;[Epub] CrossRef
Prior immunization status of COVID-19 patients and disease severity: A multicenter retrospective cohort study assessing the different types of immunity
Javaria Aslam, Faisal Shahzad Khan, Muhammad Talha Haris, Hewad Hewadmal, Maryam Khalid, Mohammad Y. Alshahrani, Qurrat-ul-ain Aslam, Irrum Aneela, Urooj Zafar
Vaccine.2023; 41(2): 598. CrossRef
Mortality and Severity of Coronavirus Disease 2019 in Patients with Long-Term Glucocorticoid Therapy: A Korean Nationwide Cohort Study
Eu Jeong Ku, Keeho Song, Kyoung Min Kim, Gi Hyeon Seo, Soon Jib Yoo
Endocrinology and Metabolism.2023; 38(2): 253. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef
Inactivated SARS-CoV-2 vaccination does not disturb the clinical course of Graves’ disease: An observational cohort study
Shichen Xu, Huixin Yu, Xian Cheng, Jing Wu, Jiandong Bao, Li Zhang
Vaccine.2023; 41(38): 5648. CrossRef
Adrenal Crisis Associated With COVID-19 Vaccination in Patients With Adrenal Insufficiency
Yukako Kurematsu, Takako Mohri, Sadanori Okada, Yutaka Takahashi
JCEM Case Reports.2023;[Epub] CrossRef
Adverse Events Associated with COVID-19 Vaccination in Adolescents with Endocrinological Disorders: A Cross-Sectional Study
İbrahim Mert Erbaş, İrem Ceren Erbaş, Gözde Akın Kağızmanlı, Kübra Yüksek Acinikli, Özge Besci, Korcan Demir, Ece Böber, Nurşen Belet, Ayhan Abacı
Journal of Clinical Research in Pediatric Endocrinology.2023; 15(3): 248. CrossRef
Neue Aspekte der Glukokortikoidsubstitution bei Nebennierenrindeninsuffizienz
Tina Kienitz, Gesine Meyer
Der Internist.2022; 63(1): 12. CrossRef
Endocrine Follow-up During Post-Acute COVID-19: Practical Recommendations Based on Available Clinical Evidence
Rimesh Pal, Ameya Joshi, Sanjay K. Bhadada, Mainak Banerjee, Suresh Vaikkakara, Satinath Mukhopadhyay
Endocrine Practice.2022; 28(4): 425. CrossRef
Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study
Xi Xiong, Carlos King Ho Wong, Ivan Chi Ho Au, Francisco Tsz Tsun Lai, Xue Li, Eric Yuk Fai Wan, Celine Sze Ling Chui, Esther Wai Yin Chan, Franco Wing Tak Cheng, Kristy Tsz Kwan Lau, Chi Ho Lee, Yu Cho Woo, David Tak Wai Lui, Ian Chi Kei Wong
Thyroid.2022; 32(5): 505. CrossRef
The New Entity of Subacute Thyroiditis amid the COVID-19 Pandemic: From Infection to Vaccine
Mihaela Popescu, Adina Ghemigian, Corina Maria Vasile, Andrei Costache, Mara Carsote, Alice Elena Ghenea
Diagnostics.2022; 12(4): 960. CrossRef
Adrenal Crisis Secondary to COVID-19 Vaccination in a Patient With Hypopituitarism
Nikolina Markovic, Anila Faizan, Chirag Boradia, Sridhar Nambi
AACE Clinical Case Reports.2022; 8(4): 171. CrossRef
The Effect of Inactivated SARS-CoV-2 Vaccines on TRAB in Graves’ Disease
LingHong Huang, ZhengRong Jiang, JingXiong Zhou, YuPing Chen, HuiBin Huang
Frontiers in Endocrinology.2022;[Epub] CrossRef
Osteoporosis in Patients With Respiratory Diseases
Yue Ma, Shui Qiu, Renyi Zhou
Frontiers in Physiology.2022;[Epub] CrossRef
Pilot Findings on SARS-CoV-2 Vaccine-Induced Pituitary Diseases: A Mini Review from Diagnosis to Pathophysiology
Ach Taieb, El Euch Mounira
Vaccines.2022; 10(12): 2004. CrossRef
Forty Years Together, New Leap Forward! The 40th Anniversary of the Korean Endocrine Society
Jong Chul Won, Ki-Hyun Baek
Endocrinology and Metabolism.2022; 37(6): 851. CrossRef
No need of glucocorticoid dose adjustment in patients with adrenal insufficiency before COVID-19 vaccine
Tania Pilli, Cristina Dalmiglio, Gilda Dalmazio, Alfonso Sagnella, Raffaella Forleo, Lucia Brilli, Fabio Maino, Cristina Ciuoli, Maria Grazia Castagna
European Journal of Endocrinology.2022; 187(1): K7. CrossRef
COVID-19 mRNA vaccine may trigger subacute thyroiditis
Mehmet Sözen, Ömercan Topaloğlu, Berrin Çetinarslan, Alev Selek, Zeynep Cantürk, Emre Gezer, Damla Köksalan, Taner Bayraktaroğlu
Human Vaccines & Immunotherapeutics.2021; 17(12): 5120. CrossRef
Diabetes and COVID-19 Vaccination
Hae Dong Choi, Jun Sung Moon
The Journal of Korean Diabetes.2021; 22(4): 221. CrossRef

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.

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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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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

Endocrine Research
Danshen Extracts Prevents Obesity and Activates Mitochondrial Function in Brown Adipose Tissue: Yoon Hee Cho, Cheol Ryong Ku, Young-Suk Choi, Hyeon Jeong Lee, Eun Jig Lee; Endocrinol Metab. 2021;36(1):185-195. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.835

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Abstract PDF PubReader ePub Crossref - TDM: Background
Danshen has been widely used in oriental medicine to improve body function. The purpose of this study is to investigate the effect of water-soluble Danshen extract (DE) on weight loss and on activation proteins involved in mitochondrial biogenesis in brown adipose tissue (BAT) in obese mice.
Methods
BAT was isolated from 7-week-old male Sprague-Dawley rats, and expression of proteins related to mitochondrial biogenesis was confirmed in both brown preadipocytes and mature brown adipocytes treated with DE. For the in vivo study, low-density lipoprotein receptor knock out mice were divided into three groups and treated for 17 weeks with: standard diet; high fat diet (HFD); HFD+DE. Body weight was measured every week, and oral glucose tolerance test was performed after DE treatment in streptozotocin-induced diabetic mice. To observe the changes in markers related to thermogenesis and adipogenesis in the BAT, white adipose tissue (WAT) and liver of experimental animals, tissues were removed and immediately frozen in liquid nitrogen.
Results
DE increased the expression of uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in brown preadipocytes, and also promoted the brown adipocyte differentiation and mitochondrial function in the mature brown adipocytes. Reactive oxygen species production in brown preadipocytes was increased depending on the concentration of DE. DE activates thermogenesis in BAT and normalizes increased body weight and adipogenesis in the liver due to HFD. Browning of WAT was increased in WAT of DE treatment group.
Conclusion
DE protects against obesity and activates mitochondrial function in BAT.

Brief Report

Hypothalamus and Pituitary gland
Establishment of Reference Intervals for Serum Insulin-Like Growth Factor I in Korean Adult Population: Boyeon Kim, Yonggeun Cho, Cheol Ryong Ku, Sang-Guk Lee, Kyung-A Lee, Jeong-Ho Kim; Endocrinol Metab. 2020;35(4):960-964. Published online November 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.732

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Appropriate reference intervals of serum insulin-like growth factor I (IGF-I) is important for diagnosing and monitoring patients with growth hormone-related diseases. To establish reference intervals, adult individuals (n=1,334, 680 men and 654 women) were divided into six age groups (20–29, 30–39, 40–49, 50–59, 60–69, ≥70). Serum IGF-I was measured by chemiluminescence immunoassay (Liaison). Concordance of patient classification based on reference intervals, manufacturer’s intervals, and standard deviation score (SDS) was evaluated. New reference intervals had higher upper and lower limits than those specified by the manufacturer. The agreement between classification using new reference interval and the manufacturer’s reference interval, and that using new reference interval and SDS was 75.0% (weighted kappa, 0.17), 91.9% (weighted kappa, 0.51) in men and 91.0% (weighted kappa, 0.41), 92.5% (weighted kappa, 0.53) in women, respectively. Reference intervals should be established not only based on age and sex, but also on ethnicity and assay method.

Citations

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Male idiopathic hypogonadotropic hypogonadism: Serum insulin-like growth factor-1 and oestradiol levels
Nastaran Salehisedeh, Amir Parhizkar, Parichehreh Yaghmaei, Marjan Sabbaghian
Journal of Human Reproductive Sciences.2022; 15(4): 351. CrossRef
Revisiting the Role of Insulin-like Growth Factor-1 Measurement After Surgical Treatment of Acromegaly
In-Ho Jung, Seonah Choi, Cheol Ryong Ku, Sang-Guk Lee, Eun Jig Lee, Sun Ho Kim, Eui Hyun Kim
The Journal of Clinical Endocrinology & Metabolism.2021; 106(7): e2589. CrossRef

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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Abstract PDF PubReader ePub Crossref - TDM

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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Evaluation of Adult Height in Patients with Non-Permanent Idiopathic GH Deficiency
Agnese Murianni, Anna Lussu, Chiara Guzzetti, Anastasia Ibba, Letizia Casula, Mariacarolina Salerno, Marco Cappa, Sandro Loche
Endocrines.2023; 4(1): 169. CrossRef
The effect of hypothalamic involvement and growth hormone treatment on cardiovascular risk factors during the transition period in patients with childhood-onset craniopharyngioma
Sang Hee Park, Yun Jeong Lee, Jung-Eun Cheon, Choong Ho Shin, Hae Woon Jung, Young Ah Lee
Annals of Pediatric Endocrinology & Metabolism.2023; 28(2): 107. CrossRef
Continuous Glucose Monitoring: A Possible Aid for Detecting Hypoglycemic Events during Insulin Tolerance Tests
Soo Yeun Sim, Moon Bae Ahn
Sensors.2023; 23(15): 6892. CrossRef
Diagnosis of GH Deficiency Without GH Stimulation Tests
Anastasia Ibba, Sandro Loche
Frontiers in Endocrinology.2022;[Epub] CrossRef
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
Endocrinology and Metabolism.2022; 37(2): 359. CrossRef
A Radiomics-Based Model with the Potential to Differentiate Growth Hormone Deficiency and Idiopathic Short Stature on Sella MRI
Taeyoun Lee, Kyungchul Song, Beomseok Sohn, Jihwan Eom, Sung Soo Ahn, Ho-Seong Kim, Seung-Koo Lee
Yonsei Medical Journal.2022; 63(9): 856. CrossRef
Phenotypic spectrum of patients with mutations in CHD7: clinical implications of endocrinological findings
Ja Hye Kim, Yunha Choi, Soojin Hwang, Gu-Hwan Kim, Han-Wook Yoo, Jin-Ho Choi
Endocrine Connections.2022;[Epub] CrossRef
Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society
Hyemi Kwon, Eun Roh, Chang Ho Ahn, Hee Kyung Kim, Cheol Ryong Ku, Kyong Yeun Jung, Ju Hee Lee, Eun Heui Kim, Sunghwan Suh, Sangmo Hong, Jeonghoon Ha, Jun Sung Moon, Jin Hwa Kim, Mi-kyung Kim
Endocrinology and Metabolism.2022; 37(6): 839. CrossRef
Laron syndrome: clinic, diagnostics (а clinical case)
P.M. Lіashuk, R.P. Lіashuk, N.I. Stankova, M.B. Kudina
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2022; 18(3): 193. CrossRef
Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force
Eu Jeong Ku, Kyoung Jin Kim, Jung Hee Kim, Mi Kyung Kim, Chang Ho Ahn, Kyung Ae Lee, Seung Hun Lee, You-Bin Lee, Kyeong Hye Park, Yun Mi Choi, Namki Hong, A Ram Hong, Sang-Wook Kang, Byung Kwan Park, Moon-Woo Seong, Myungshin Kim, Kyeong Cheon Jung, Chan
Endocrinology and Metabolism.2021; 36(2): 322. CrossRef
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Byung Kwan Park, Masashi Fujimori, Shu-Huei Shen, Uei Pua
Endocrinology and Metabolism.2021; 36(3): 553. CrossRef
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Byung Kwan Park, Shu-Huei Shen, Masashi Fujimori, Yi Wang
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The Korean Journal of Medicine.2021; 96(5): 400. CrossRef

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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Abstract PDF PubReader ePub Crossref - TDM

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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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; 99(17): e1875. 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

Original Article

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

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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Abstract PDF PubReader ePub Crossref - TDM

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.

Citations

Citations to this article as recorded by

Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association
A Ram Hong, Ho-Cheol Kang
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Response

Obesity and Metabolism
Response: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes (Endocrinol Metab 2016;31:328-35, Cheol Ryong Ku et al.): Cheol Ryong Ku, Eun Jig Lee; Endocrinol Metab. 2016;31(3):482-483. Published online September 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.482

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Mitochondrial oxidative stress in obesity: role of the mineralocorticoid receptor
Clara Lefranc, Malou Friederich-Persson, Roberto Palacios-Ramirez, Aurelie Nguyen Dinh Cat
Journal of Endocrinology.2018; 238(3): R143. CrossRef

Original Articles

Endocrine Research
The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes: Cheol Ryong Ku, Yoon Hee Cho, Zhen-Yu Hong, Ha Lee, Sue Ji Lee, Seung-soo Hong, Eun Jig Lee; Endocrinol Metab. 2016;31(2):328-335. Published online April 8, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.328

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Background

Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes.

Methods

For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments.

Results

RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group.

Conclusion

RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.

Citations

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Juan Salazar, Clímaco Cano, José L. Pérez, Ana Castro, María P. Díaz, Bermary Garrido, Rubén Carrasquero, Maricarmen Chacín, Manuel Velasco, Luis D´Marco, Joselyn Rojas-Quintero, Valmore Bermúdez
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Alba Serrano, Madhu Asnani-Kishnani, Ana María Rodríguez, Andreu Palou, Joan Ribot, María Luisa Bonet
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Effects of Polyphenols on Thermogenesis and Mitochondrial Biogenesis
Tanila Wood dos Santos, Quélita Cristina Pereira, Lucimara Teixeira, Alessandra Gambero, Josep A. Villena, Marcelo Lima Ribeiro
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Perla P. Argentato, Helena de Cássia César, Débora Estadella, Luciana P. Pisani
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Response: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes (Endocrinol Metab2016;31:328-35, Cheol Ryong Ku et al.)
Cheol Ryong Ku, Eun Jig Lee
Endocrinology and Metabolism.2016; 31(3): 482. CrossRef
Letter: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes (Endocrinol Metab2016;31:328-35, Cheol Ryong Ku et al.)
Ji-Young Cha
Endocrinology and Metabolism.2016; 31(3): 480. CrossRef

Adrenal gland
Early Prediction of Long-Term Response to Cabergoline in Patients with Macroprolactinomas: Youngki Lee, Cheol Ryong Ku, Eui-Hyun Kim, Jae Won Hong, Eun Jig Lee, Sun Ho Kim; Endocrinol Metab. 2014;29(3):280-292. Published online September 25, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.3.280

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Background

Cabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline.

Methods

We retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated.

Results

Forty patients (90.9%) were treated medically and displayed tumor volume reduction (TVR) of 74.7%, a prolactin normalization (NP) rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery) rate of 70.5%. Most patients (93.1%) with TVR ≥25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR ≥25% without NP and no patients with TVR <25% achieved CR. TVR at 3 months was strongly correlated with final TVR (R=0.785). Patients with large macroadenomas exhibited a low NP rate at 3 months, but eventually achieved TVR and NP rates similar to those of patients with smaller tumors. Surgery independently reduced the final dose of cabergoline (β=-1.181 mg/week), and two of four patients who underwent surgery were able to discontinue cabergoline.

Conclusion

Determining cabergoline response using TVR and NP 3 months after treatment is useful for predicting later outcomes. However, further cabergoline administration should be considered for patients with TVR >25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.

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Review Article

Adrenal gland
Characteristics of Acromegaly in Korea with a Literature Review: Jae Won Hong, Cheol Ryong Ku, Sun Ho Kim, Eun Jig Lee; Endocrinol Metab. 2013;28(3):164-168. Published online September 13, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.3.164

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Acromegaly is a slowly progressive disease caused by excessive growth hormone (GH), which is related to a GH secreting pituitary tumor in most cases. Herein, we describe the epidemiology, clinical characteristics, and treatment of acromegaly in Korea with a literature review. The average annual incidence of acromegaly in Korea was 3.9 cases per million people, which was within the range of previous Western studies. The primary treatment for acromegaly was also transsphenoidal adenomectomy, which accounted for 90.4% of patients whose primary therapeutic options were known. The overall surgical remission rates were 89%, 87%, 64%, 70%, and 50% for modified Hardy classification I, II, IIIA, IIIB, and IV, respectively. An updated and larger study regarding the treatment outcome of medical/radiotherapy in Korean acromegalic patients is needed.

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Problems of Endocrinology.2021; 67(1): 20. CrossRef
Precision Therapy in Acromegaly Caused by Pituitary Tumors: How Close Is It to Reality?
Cheol Ryong Ku, Vladimir Melnikov, Zhaoyun Zhang, Eun Jig Lee
Endocrinology and Metabolism.2020; 35(2): 206. CrossRef
Patient Characteristics, Diagnostic Delays, Treatment Patterns, Treatment Outcomes, Comorbidities, and Treatment Costs of Acromegaly in China: A Nationwide Study
Xiaopeng Guo, Kailu Wang, Siyue Yu, Lu Gao, Zihao Wang, Huijuan Zhu, Bing Xing, Shuyang Zhang, Dong Dong
Frontiers in Endocrinology.2020;[Epub] CrossRef
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Case Report

A Case of Pituitary Adenoma with Simultaneous Secretion of TSH and GH.: Eun Young Lee, Cheol Ryong Ku, Hyun Min Kim, Woo Kyoung Lee, Jung Soo Lim, Sena Hwang, Do Hwan Kim, Dong Yeob Shin, Eun Jig Lee; Endocrinol Metab. 2011;26(2):160-165. Published online June 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.2.160

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Abstract PDF

Thyrotropin (TSH)-secreting pituitary adenoma is a very rare disease. In one-quarter of patients suffering from this disease, the pituitary tumor secretes other anterior pituitary hormones. Herein, we report a case of pituitary adenoma with simultaneous secretion of TSH and growth hormone (GH). A 34-year-old female visitied local hospital complaining of sweating, intermittent palpitation, and weight loss of 8 kg within 1 year. The patient had undergone trans-sphenoidal surgery 3 years prior for resolution of a TSH and GH co-secreting pituitary adenoma. She had been administered somatostatin analogue prior to visiting our hospital. The patient's GH levels were suppressed to below 1 ng/mL on the 75 g oral glucose tolerance test, and her basal insulin-like growth factor-I (IGF-I) level was within normal range. Thyroid function tests demonstrated increased levels of both free thyroxine and TSH. Sella-MRI revealed pituitary adenoma at the floor of the pituitary fossa, approximately 2 cm in height. Therefore, she was diagnosed with residual TSH-secreting pituitary adenoma. The patient again underwent trans-sphenoidal surgery and entered complete remission, based on hormone levels and MRI findings.

Citations

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Endoscopic Transsphenoidal Surgery of Pituitary Adenomas: Preliminary Results of the Neurosurgery Service of Hospital Cristo Redentor
Gerson Perondi, Afonso Mariante, Fernando Azambuja, Gabriel Frizon Greggianin, Wanderson William dos Santos Dias, Giulia Pinzetta
Arquivos Brasileiros de Neurocirurgia: Brazilian Neurosurgery.2023; 42(02): e89. CrossRef
A case of a co-secreting TSH and growth hormone pituitary adenoma presenting with a thyroid nodule
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Endocrinology, Diabetes & Metabolism Case Reports.2018;[Epub] CrossRef

Original Article

Correlation between Pituitary Insufficiency and Magnetic Resonance Imaging Finding in Non-Functioning Pituitary Adenomas.: Hyun Min Kim, Cheol Ryong Ku, Eun Young Lee, Woo Kyung Lee, Jung Soo Lim, Sena Hwang, Mi Jung Lee, Seung Ku Lee, Sun Ho Kim, Eun Jig Lee; Endocrinol Metab. 2010;25(4):310-315. Published online December 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.4.310

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Abstract PDF

BACKGROUND
Non-functioning pituitary adenomas (NFPAs) are characterized by the absence of clinical and biochemical evidence of pituitary hormone hypersecretion, and these tumors constitute approximately one third of all the tumors of the anterior pituitary. Recently, hormonal deficiencies have gradually evolved to become the leading presenting signs and symptoms in patients with NFPAs. We investigated pituitary hormonal insufficiencies according to the magnetic resonance imaging (MRI) findings in patients with NFPA. METHODS: We evaluated the patients who were newly diagnosed with NFPA from 1997 through 2009. Among them, we analyzed 387 patients who were tested for their combined pituitary function and who underwent MRI. The severity of the hypopituitarism was determined by the number of deficient axes of the pituitary hormones. On the MRI study, the maximal diameter of the tumor, Hardy's classification, the thickness of the pituitary gland and the presence of stalk compression were evaluated. RESULTS: The mean age was 46.85 +/- 12.93 years (range: 15-86) and 186 patients (48.1%) were male. As assessed on MRI, the tumor diameter was 27.87 +/- 9.93 mm, the thickness of the normal pituitary gland was 1.42 +/- 2.07 mm and stalk compression was observed in 201 patients (51.9%). Hypopituitarism was observed in 333 patients (86.0%). Deficiency for each pituitary hormone was most severe in the patients with Hardy type IIIA. Hypopituitarism was severe in the older age patients (P = 0.001) and the patients with a bigger tumor size (P < 0.001) and the presence of stalk compression (P < 0.001). However, the patients who had a thicker pituitary gland showed less severe hypopituitarism (P < 0.001). Multivariate analysis showed that age, tumor diameter and the thickness of pituitary gland were important determinants for pituitary deficiency (P = 0.004, P < 0.001, P = 0.022, respectively). CONCLUSION: The results suggest that the hormonal deficiencies in patient with NFPA were correlated with the MRI findings, and especially the tumor diameter and preservation of the pituitary gland.

Citations

Citations to this article as recorded by

Clinical Parameters to Distinguish Silent Corticotroph Adenomas from Other Nonfunctioning Pituitary Adenomas
Daham Kim, Cheol Ryong Ku, Se Hee Park, Ju Hyung Moon, Eui Hyun Kim, Sun Ho Kim, Eun Jig Lee
World Neurosurgery.2018; 115: e464. CrossRef

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