Endocrinology and Metabolism

Namgok Lecture 2023

Diabetes, obesity and metabolism
Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator: Se Hee Min, Do Kyeong Song, Chan Hee Lee, Eun Roh, Min-Seon Kim; Endocrinol Metab. 2024;39(1):1-11. Published online February 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.1922

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Abstract PDF PubReader ePub: 5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a cellular energy sensor, is an essential enzyme that helps cells maintain stable energy levels during metabolic stress. The hypothalamus is pivotal in regulating energy balance within the body. Certain neurons in the hypothalamus are sensitive to fluctuations in food availability and energy stores, triggering adaptive responses to preserve systemic energy equilibrium. AMPK, expressed in these hypothalamic neurons, is instrumental in these regulatory processes. Hypothalamic AMPK activity is modulated by key metabolic hormones. Anorexigenic hormones, including leptin, insulin, and glucagon-like peptide 1, suppress hypothalamic AMPK activity, whereas the hunger hormone ghrelin activates it. These hormonal influences on hypothalamic AMPK activity are central to their roles in controlling food consumption and energy expenditure. Additionally, hypothalamic AMPK activity responds to variations in glucose concentrations. It becomes active during hypoglycemia but is deactivated when glucose is introduced directly into the hypothalamus. These shifts in AMPK activity within hypothalamic neurons are critical for maintaining glucose balance. Considering the vital function of hypothalamic AMPK in the regulation of overall energy and glucose balance, developing chemical agents that target the hypothalamus to modulate AMPK activity presents a promising therapeutic approach for metabolic conditions such as obesity and type 2 diabetes mellitus.

Special Article

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.

Citations

Citations to this article as recorded by

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
Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review
Won Sang Yoo, Eu Jeong Ku, Eun Kyung Lee, Hwa Young Ahn
Endocrinology and Metabolism.2023; 38(6): 750. CrossRef

Brief Report

Diabetes, Obesity and Metabolism
Sestrin2 Regulates Beneficial β3-Adrenergic Receptor-Mediated Effects Observed in Inguinal White Adipose Tissue and Soleus Muscle: Min Jeong Park, Joo Won Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, Hye Jin Yoo; Endocrinol Metab. 2022;37(3):552-557. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1421

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Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.

Citations

Citations to this article as recorded by

Sestrin2 levels in patients with anxiety and depression myocardial infarction was up-regulated and suppressed inflammation and ferroptosis by LKB1-mediated AMPK activation
Yufeng Qian, Lian Chen, Beibei Gao, Xianhua Ye
Clinical and Experimental Hypertension.2023;[Epub] CrossRef
Sestrin2 in diabetes and diabetic complications
Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li
Frontiers in Endocrinology.2023;[Epub] CrossRef

Original Article

Thyroid Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes in Patients with Long-Standing Graves’ Disease: A Longitudinal Study: Eyun Song, Min Ji Koo, Eunjin Noh, Soon Young Hwang, Min Jeong Park, Jung A Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Geum Joon Cho, Hye Jin Yoo; Endocrinol Metab. 2021;36(6):1277-1286. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1251

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Background
The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies.
Methods
The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group.
Results
A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019).
Conclusion
The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

Citations

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Nadia Sawicka-Gutaj, Dawid Gruszczyński, Natalia Zawalna, Kacper Nijakowski, Agnieszka Skiba, Mateusz Pochylski, Jerzy Sowiński, Marek Ruchała
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Increased risk of diabetes mellitus and hyperlipidemia in patients with differentiated thyroid cancer
Hwa Young Ahn, Jooyoung Lee, Jinmo Kang, Eun Kyung Lee
European Journal of Endocrinology.2024; 190(3): 248. CrossRef
Prevalencia de diabetes en personas con disfunción tiroidea
Juan J. Díez, Pedro Iglesias
Medicina Clínica.2023; 160(8): 333. CrossRef
Control of Thyroid Dysfunction in Spanish Population Registered in the Primary Care Clinical Database: An Analysis of the Proportion of Patients with Thyrotropin Values Outside the Reference Range
Juan J. Díez, Pedro Iglesias
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Juan J. Díez, Pedro Iglesias
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Juan J. Díez, Pedro Iglesias
Medicina Clínica (English Edition).2023; 160(8): 333. CrossRef
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Mihaela Simona Popoviciu, Lorena Paduraru, Raluca Marinela Nutas, Alexandra Maria Ujoc, Galal Yahya, Kamel Metwally, Simona Cavalu
International Journal of Molecular Sciences.2023; 24(16): 12676. CrossRef
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Roshmi Gupta, Pramila Kalra, Lakshmi B. Ramamurthy, Suryasnata Rath
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Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves’ Disease
Ho Yeop Lee, Byeong Chang Sim, Ha Thi Nga, Ji Sun Moon, Jingwen Tian, Nguyen Thi Linh, Sang Hyeon Ju, Dong Wook Choi, Daiki Setoyama, Hyon-Seung Yi
Endocrinology and Metabolism.2022; 37(6): 891. CrossRef
Diabetes and Hyperthyroidism: Is There a Causal Link?
Sang Yong Kim
Endocrinology and Metabolism.2021; 36(6): 1175. CrossRef

Special Article

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.

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C. Ouaddouh, J.W. Duijster, T. Lieber, F.P.A.M. van Hunsel
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David Tak Wai Lui, Chi Ho Lee, Yu Cho Woo, Ivan Fan Ngai Hung, Karen Siu Ling Lam
Nature Reviews Endocrinology.2024;[Epub] CrossRef
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Hyeyeon Moon, Sunghwan Suh, Mi Kyoung Park
Journal of Korean Medical Science.2023;[Epub] CrossRef
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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
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Eu Jeong Ku, Keeho Song, Kyoung Min Kim, Gi Hyeon Seo, Soon Jib Yoo
Endocrinology and Metabolism.2023; 38(2): 253. CrossRef
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Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef
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Shichen Xu, Huixin Yu, Xian Cheng, Jing Wu, Jiandong Bao, Li Zhang
Vaccine.2023; 41(38): 5648. CrossRef
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Yukako Kurematsu, Takako Mohri, Sadanori Okada, Yutaka Takahashi
JCEM Case Reports.2023;[Epub] CrossRef
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İbrahim Mert Erbaş, İrem Ceren Erbaş, Gözde Akın Kağızmanlı, Kübra Yüksek Acinikli, Özge Besci, Korcan Demir, Ece Böber, Nurşen Belet, Ayhan Abacı
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Rimesh Pal, Ameya Joshi, Sanjay K. Bhadada, Mainak Banerjee, Suresh Vaikkakara, Satinath Mukhopadhyay
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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
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Review Article

Obesity and Metabolism
Brain Regulation of Energy Metabolism: Eun Roh, Min-Seon Kim; Endocrinol Metab. 2016;31(4):519-524. Published online December 20, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.519

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In healthy individuals, energy intake is in balance with energy expenditure, which helps to maintain a normal body weight. The brain's inability to control energy homeostasis underlies the pathology of hyperphagia and obesity. The brain detects body energy excess and deficit by sensing the levels of circulating metabolic hormones and nutrients and by receiving metabolic information from the periphery via the autonomic nervous system. A specialized neuronal network coordinates energy intake behavior and the metabolic processes affecting energy expenditure. Here, we briefly review neuronal mechanisms by which our body maintains energy balance.

Citations

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Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator
Se Hee Min, Do Kyeong Song, Chan Hee Lee, Eun Roh, Min-Seon Kim
Endocrinology and Metabolism.2024; 39(1): 1. CrossRef
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Original Article

Clinical Study
Radiographic Characteristics of Adrenal Masses in Oncologic Patients: Ji Hyun Lee, Eun Ky Kim, A Ram Hong, Eun Roh, Jae Hyun Bae, Jung Hee Kim, Chan Soo Shin, Seong Yeon Kim, Sang Wan Kim; Endocrinol Metab. 2016;31(1):147-152. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.147

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Background

We aimed to assess the usefulness of pre-contrast Hounsfield unit (HU) and mass size on computed tomography to differentiate adrenal mass found incidentally in oncologic patients.

Methods

From 2000 to 2012, 131 oncologic patients with adrenal incidentaloma were reviewed retrospectively. Receiver operating characteristic (ROC) curves were applied to determine the optimal cut-off value of the mean HU and size for detecting adrenal metastasis.

Results

The median age was 18 years, and 80 patients were male. The initial mass size was 18 mm, and 71 (54.2%) of these were on the left side. A bilateral adrenal mass was found in 11 patients (8.4%). Biochemically functional masses were observed in 9.2% of patients. Thirty-six out of 119 patients with nonfunctional masses underwent adrenalectomy, which revealed metastasis in 13. The primary cancers were lung cancer (n=4), renal cell carcinoma (n=2), lymphoma (n=2), hepatocellular carcinoma (n=2), breast cancer (n=1), and others (n=2). The area under the curve for the size and HU for clinically suspicious metastasis were 0.839 (95% confidence interval [CI], 0.761 to 0.900; P<0.001) and 0.959 (95% CI, 0.898 to 0.988; P<0.001), respectively. The cut-off value to distinguish between metastasis and benign masses were 22 mm for size and 20 for HU.

Conclusion

ROC curve results suggest that pre-contrast HU >20 can be used as a diagnostic reference to suggest metastasis in oncologic patients with adrenal masses.

Citations

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Adrenal Tumors Found During Staging and Surveillance for Colorectal Cancer: Benign Incidentalomas or Metastatic Disease?
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World Journal of Surgery.2020; 44(7): 2282. CrossRef
Predictive factors for adrenal metastasis in extra‐adrenal malignancy patients with solitary adrenal mass
Kyeong‐Hyeon Byeon, Yun‐Sok Ha, Seock‐Hwan Choi, Bum Soo Kim, Hyun Tae Kim, Eun Sang Yoo, Tae Gyun Kwon, Jun Nyung Lee, Tae‐Hwan Kim
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Combining Washout and Noncontrast Data From Adrenal Protocol CT
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Evaluation of quantitative parameters for distinguishing pheochromocytoma from other adrenal tumors
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Case Report

Thyroid
Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease: Eun Roh, Ye An Kim, Eu Jeong Ku, Jae Hyun Bae, Hye Mi Kim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Soo Heon Kwak; Endocrinol Metab. 2013;28(1):55-60. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.55

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We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

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Original Article

Characterization of Incidentally Detected Adrenal Pheochromocytoma.: Ye An Kim, Yul Hwangbo, Min Joo Kim, Hyung Jin Choi, Je Hyun Seo, Yenna Lee, Soo Heun Kwak, Eu Jeong Ku, Tae Jung Oh, Eun Roh, Jae Hyun Bae, Jung Hee Kim, Kyoung Soo Park, Seong Yeon Kim; Endocrinol Metab. 2012;27(2):132-137. Published online June 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.2.132

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Abstract PDF

BACKGROUND
In approach to an adrenal incidentaloma, early exclusion of pheochromocytoma is clinically important, due to the risk of catecholamine crisis. The aims of this study are to investigate the characteristics of incidentally detected pheochromocytomas, compared with that of the other adrenal incidentalomas, and to compare these characteristics with those of symptomatic pheochromocytomas. METHODS: In this retrospective study, we reviewed the medical records of 198 patients with adrenal incidentaloma from 2001 to 2010. We analyzed the clinical, laboratory and radiological data of pheochromocytomas, in comparison with those of the other adrenal incidentalomas. We also compared the characteristics of these incidentally detected pheochromocytomas with the medical records of 28 pathologically proven pheochromocytomas, diagnosed based on typical symptoms. RESULTS: Among the 198 patients with adrenal incidentaloma, nineteen patients were diagnosed with pheochromocytoma. Pheochromocytomas showed larger size and higher Hounsfield unit at precontrast computed tomography (CT) than did non-pheochromocytomas. All pheochromocytomas were larger than 2.0 cm, and the Hounsfield units were 19 or higher in precontrast CT. When both criteria of size > 2.0 cm and Hounsfield unit > 19 were met, the sensitivity and specificity for the diagnosis of pheochromocytoma were 100% and 79.3%, respectively. Compared with patients with pheochromocytoma, diagnosed based on typical symptoms, patients with incidentally detected pheochromocytoma were older, presented less often with hypertension, and showed lower levels of 24-hour urine metanephrine. CONCLUSION: Adrenal incidentaloma with < 2.0 cm in size or < or = 19 Hounsfield units in precontrast CT imaging was less likely to be a pheochromocytoma. Patients with incidentally discovered pheochromocytoma showed lower catecholamine metabolites, compared with those patients with symptomatic pheochromocytoma.

Citations

Citations to this article as recorded by

Guidelines for the Management of Adrenal Incidentaloma: the Korean Endocrine Society, Committee of Clinical Practice Guidelines
Jung-Min Lee, Mee Kyoung Kim, Seung-Hyun Ko, Jung-Min Koh, Bo-Yeon Kim, Sang-Wan Kim, Soo-Kyung Kim, Hae-Jin Kim, Ohk-Hyun Ryu, Juri Park, Jung-Soo Lim, Seong Yeon Kim, Young Kee Shong, Soon Jib Yoo
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Jung-Min Lee, Mee Kyoung Kim, Seung-Hyun Ko, Jung-Min Koh, Bo-Yeon Kim, Sang Wan Kim, Soo-Kyung Kim, Hae Jin Kim, Ohk-Hyun Ryu, Juri Park, Jung Soo Lim, Seong Yeon Kim, Young Kee Shong, Soon Jib Yoo
Endocrinology and Metabolism.2017; 32(2): 200. CrossRef
Characterization of Incidentally Detected Adrenal Pheochromocytoma
Soon Jib Yoo, Woohyeon Kim
Endocrinology and Metabolism.2012; 27(2): 116. CrossRef

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