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Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer
Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park
Endocrinol Metab. 2023;38(6):619-630.   Published online November 21, 2023
DOI: https://doi.org/10.3803/EnM.2023.1814
  • 4,140 View
  • 137 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing’s syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing’s syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

Citations

Citations to this article as recorded by  
  • Editorial: Tumor metabolism and programmed cell death
    Dan-Lan Pu, Qi-Nan Wu
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies
    Han Wang, Yang Liu, Aifa Tang, Xiansheng Zhang
    European Journal of Medical Research.2024;[Epub]     CrossRef
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Brief Report
Adrenal Gland
Urinary Free Metanephrines for Diagnosis of Pheochromocytoma and Paraganglioma
Jiyeon Ahn, Ji Yun Park, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Soo-Youn Lee, Jae Hyeon Kim
Endocrinol Metab. 2021;36(3):697-701.   Published online June 1, 2021
DOI: https://doi.org/10.3803/EnM.2020.925
  • 6,111 View
  • 205 Download
  • 4 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated.
Methods
This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group.
Results
Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity.
Conclusion
Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.

Citations

Citations to this article as recorded by  
  • Advancements in understanding the molecular mechanisms and clinical implications of Von Hippel-Lindau syndrome: A comprehensive review
    Yaochun Wang, Jingzhuo Song, Shuxing Zheng, Shuhong Wang
    Translational Oncology.2025; 51: 102193.     CrossRef
  • The role of the adrenalectomy in the management of pheochromocytoma: the experience of a Portuguese referral center
    Inês Costa Carvalho, Miguel V. B. Machado, João P. Morais, Filipa Carvalho, Elisabete Barbosa, José Barbosa
    Endocrine.2024; 86(1): 409.     CrossRef
  • Laparoscopic Resection of Para-Aortic Mass at the Aortic Bifurcation: An Atypical Presentation of a Tailgut Cyst
    Andy Wang, Jiddu A Guart, Danielle Li, Trenton Taros, Hongyi Cui
    Cureus.2024;[Epub]     CrossRef
  • Biochemical Assessment of Pheochromocytoma and Paraganglioma
    Graeme Eisenhofer, Christina Pamporaki, Jacques W M Lenders
    Endocrine Reviews.2023; 44(5): 862.     CrossRef
  • Adrenal bleeding due to pheochromocytoma - A call for algorithm
    Ewelina Rzepka, Joanna Kokoszka, Anna Grochowska, Magdalena Ulatowska-Białas, Martyna Lech, Marta Opalińska, Elwira Przybylik-Mazurek, Aleksandra Gilis-Januszewska, Alicja Hubalewska-Dydejczyk
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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Special Article
Adrenal gland
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 Kwon Jung, Young Seok Cho, Jin Chul Paeng, Jae Hyeon Kim, Ohk-Hyun Ryu, Yumie Rhee, Chong Hwa Kim, Eun Jig Lee
Endocrinol Metab. 2021;36(2):322-338.   Published online April 6, 2021
DOI: https://doi.org/10.3803/EnM.2020.908
  • 9,589 View
  • 687 Download
  • 11 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   ePub   
Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

Citations

Citations to this article as recorded by  
  • A Prospective Comparative Study of 18F-FDOPA PET/CT Versus 123I-MIBG Scintigraphy With SPECT/CT for the Diagnosis of Pheochromocytoma and Paraganglioma
    Changhwan Sung, Hyo Sang Lee, Dong Yun Lee, Yong-il Kim, Jae Eun Kim, Sang Ju Lee, Seung Jun Oh, Tae-Yon Sung, Yu-Mi Lee, Young Hoon Kim, Beom-Jun Kim, Jung-Min Koh, Seung Hun Lee, Jin-Sook Ryu
    Clinical Nuclear Medicine.2024; 49(1): 27.     CrossRef
  • Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study
    Seung Shin Park, Chang Ho Ahn, Seunghoo Lee, Woochang Lee, Won Woong Kim, Yu‐Mi Lee, Su Jin Kim, Tae‐Yon Sung, Kyu Eun Lee, Jung Hee Kim, Seung Hun Lee, Jung‐Min Koh
    Journal of Internal Medicine.2024; 296(1): 68.     CrossRef
  • Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review
    Kwan Hoon Jo, Jaewoong Lee, Jaeeun Yoo, Hoon Seok Kim, Eun Sook Kim, Je Ho Han, Yi Sun Jang, Jae-Seung Yun, Jang Won Son, Soon Jib Yoo, Seung Hwan Lee, Dong Jun Lim, Hyuk-Sang Kwon, Seungok Lee, Sungdae Moon, Myungshin Kim
    Annals of Laboratory Medicine.2024; 44(6): 591.     CrossRef
  • Raccomandazioni della lista del GdS-Endocrinologia e Malattie del Metabolismo SIPMeL-Choosing wisely: tiroide, anticorpi anti-tiroide, cortisolo, surrene, vitamina D: aggiornamento 2024
    Romolo M. DORIZZI, Vincenzo BRESCIA, Marina VITILLO, Ottavia PORZIO, Federica D’AURIZIO
    La Rivista Italiana della Medicina di Laboratorio.2024;[Epub]     CrossRef
  • Screening and treatment of endocrine hypertension focusing on adrenal gland disorders: a narrative review
    Seung Min Chung
    Journal of Yeungnam Medical Science.2024; 41(4): 269.     CrossRef
  • Clinical and epidemiological characteristics of patients with pheochromocytoma and retroperitoneal paraganglioma
    D. V. Rebrova, N. V. Vorokhobina
    Meditsinskiy sovet = Medical Council.2024; (16): 206.     CrossRef
  • 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
    Endocrinology and Metabolism.2023; 38(2): 175.     CrossRef
  • Lesion-based indicators predict long-term outcomes of pheochromocytoma and paraganglioma– SIZEPASS
    Helena Hanschell, Salvador Diaz-Cano, Alfredo Blanes, Nadia Talat, Gabriele Galatá, Simon Aylwin, Klaus Martin Schulte
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Interleukin-6-producing paraganglioma as a rare cause of systemic inflammatory response syndrome: a case report
    Yin Young Lee, Seung Min Chung
    Journal of Yeungnam Medical Science.2023; 40(4): 435.     CrossRef
  • (Extremely rare intrapericardial location of paraganglioma)
    Jaroslav Zajíc, Aleš Mokráček, Ladislav Pešl, Jiří Haniš, Dita Schaffelhoferová
    Cor et Vasa.2023; 65(4): 692.     CrossRef
  • A Case of Von Hippel-Lindau Disease With Recurrence of Paraganglioma and No Other Associated Symptoms: The Importance of Genetic Testing and Establishing Follow-Up Policies
    Naoki Okada, Akihiro Shioya, Sumihito Togi, Hiroki Ura, Yo Niida
    Cureus.2023;[Epub]     CrossRef
  • KSNM60 in Nuclear Endocrinology: from the Beginning to the Future
    Chae Moon Hong, Young Jin Jeong, Hae Won Kim, Byeong-Cheol Ahn
    Nuclear Medicine and Molecular Imaging.2022; 56(1): 17.     CrossRef
  • Change of Computed Tomography-Based Body Composition after Adrenalectomy in Patients with Pheochromocytoma
    Yousun Ko, Heeryoel Jeong, Seungwoo Khang, Jeongjin Lee, Kyung Won Kim, Beom-Jun Kim
    Cancers.2022; 14(8): 1967.     CrossRef
  • Evaluation and Management of Bone Health in Patients with Thyroid Diseases: a Position Statement from the Korean Thyroid Association
    A Ram Hong, Hwa Young Ahn, Bu Kyung Kim, Seong Hee Ahn, So Young Park, Min-Hee Kim, Jeongmin Lee, Sun Wook Cho, Ho-Cheol Kang
    International Journal of Thyroidology.2022; 15(1): 1.     CrossRef
  • Pheochromocytoma with Retroperitoneal Metastasis: A Case Report
    建新 崔
    Advances in Clinical Medicine.2021; 11(05): 2239.     CrossRef
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Original Articles
Clinical Study
Whole Exome Sequencing Identifies Novel Genetic Alterations in Patients with Pheochromocytoma/Paraganglioma
Soo Hyun Seo, Jung Hee Kim, Man Jin Kim, Sung Im Cho, Su Jin Kim, Hyein Kang, Chan Soo Shin, Sung Sup Park, Kyu Eun Lee, Moon-Woo Seong
Endocrinol Metab. 2020;35(4):909-917.   Published online December 23, 2020
DOI: https://doi.org/10.3803/EnM.2020.756
  • 6,293 View
  • 170 Download
  • 10 Web of Science
  • 9 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Pheochromocytoma and paragangliomas (PPGL) are known as tumors with the highest level of heritability, approximately 30% of all cases. Clinical practice guidelines of PPGL recommend genetic testing for germline variants in all patients. In this study, we used whole exome sequencing to identify novel causative variants associated with PPGL to improve the detection of rare genetic variants in our cohort.
Methods
Thirty-six tested negative for pathogenic variants in previous Sanger sequencing or targeted gene panel testing for PPGL underwent whole exome sequencing. Whole exome sequencing was performed using DNA samples enriched using TruSeq Custom Enrichment Kit and sequenced with MiSeq (Illumina Inc.). Sequencing alignment and variant calling were performed using SAMtools.
Results
Among previously mutation undetected 36 patients, two likely pathogenic variants and 13 variants of uncertain significance (VUS) were detected in 32 pheochromocytoma-related genes. SDHA c.778G>A (p.Gly260Arg) was detected in a patient with head and neck paraganglioma, and KIF1B c.2787-2A>C in a patient with a bladder paraganglioma. Additionally, a likely pathogenic variant in BRCA2, VUS in TP53, and VUS in NFU1 were detected.
Conclusion
Exome sequencing further identified genetic alterations by 5.6% in previously mutation undetected patients in PPGL. Implementation of targeted gene sequencing consisted of extended genes of PPGL in routine clinical screening can support the level of comprehensive patient assessment.

Citations

Citations to this article as recorded by  
  • Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma
    Susan Richter, Nicole Bechmann
    Journal of the Endocrine Society.2024;[Epub]     CrossRef
  • Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review
    Kwan Hoon Jo, Jaewoong Lee, Jaeeun Yoo, Hoon Seok Kim, Eun Sook Kim, Je Ho Han, Yi Sun Jang, Jae-Seung Yun, Jang Won Son, Soon Jib Yoo, Seung Hwan Lee, Dong Jun Lim, Hyuk-Sang Kwon, Seungok Lee, Sungdae Moon, Myungshin Kim
    Annals of Laboratory Medicine.2024; 44(6): 591.     CrossRef
  • Case Report: Aggressive neural crest tumors in a child with familial von Hippel Lindau syndrome associated with a germline VHL mutation (c.414A>G) and a novel KIF1B gene mutation
    Lucie Landen, Anne De Leener, Manon Le Roux, Bénédicte Brichard, Selda Aydin, Dominique Maiter, Philippe A. Lysy
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • A Case of Pheochromocytoma as a Subsequent Neoplasm in a Survivor of Childhood Embryonal Rhabdomyosarcoma
    Rozalyn L. Rodwin, Sanyukta K. Janardan, Erin W. Hofstatter, Nina S. Kadan-Lottick
    Journal of Pediatric Hematology/Oncology.2022; 44(2): e585.     CrossRef
  • Mutations of 1p genes do not consistently abrogate tumor suppressor functions in 1p-intact neuroblastoma
    Chik Hong Kuick, Jia Ying Tan, Deborah Jasmine, Tohari Sumanty, Alvin Y. J. Ng, Byrrappa Venkatesh, Huiyi Chen, Eva Loh, Sudhanshi Jain, Wan Yi Seow, Eileen H. Q. Ng, Derrick W. Q. Lian, Shui Yen Soh, Kenneth T. E. Chang, Zhi Xiong Chen, Amos H. P. Loh
    BMC Cancer.2022;[Epub]     CrossRef
  • A case of juvenile-onset pheochromocytoma with KIF1B p.V1529M germline mutation
    Masahiro Nezu, Yosuke Hirotsu, Kenji Amemiya, Miho Katsumata, Tomomi Watanabe, Soichi Takizawa, Masaharu Inoue, Hitoshi Mochizuki, Kyoko Hosaka, Toshio Oyama, Masao Omata
    Endocrine Journal.2022; 69(6): 705.     CrossRef
  • Systematic analysis of expression profiles and prognostic significance for MMDS-related iron–sulfur proteins in renal clear cell carcinoma
    Ling Yang, Yu-Xin Chen, Ying-Ying Li, Xiao-Juan Liu, Yong-Mei Jiang, Jia Mai
    Scientific Reports.2022;[Epub]     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
  • Recurrent Germline Mutations of CHEK2 as a New Susceptibility Gene in Patients with Pheochromocytomas and Paragangliomas
    Yinjie Gao, Chao Ling, Xiaosen Ma, Huiping Wang, Yunying Cui, Min Nie, Anli Tong, Dario De Biase
    International Journal of Endocrinology.2021; 2021: 1.     CrossRef
Close layer
Clinical Study
Genetic Analysis and Clinical Characteristics of Hereditary Pheochromocytoma and Paraganglioma Syndrome in Korean Population
Heewon Choi, Kyoung Jin Kim, Namki Hong, Saeam Shin, Jong-Rak Choi, Sang Wook Kang, Seung Tae Lee, Yumie Rhee
Endocrinol Metab. 2020;35(4):858-872.   Published online December 23, 2020
DOI: https://doi.org/10.3803/EnM.2020.683
  • 5,811 View
  • 204 Download
  • 13 Web of Science
  • 13 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Pheochromocytoma and paragangliomas (PPGL) are hereditary in approximately 30% to 40% cases. With the advancement of genetic analysis techniques, including next-generation sequencing (NGS), there were attempts to classify PPGL into molecular clusters. With NGS being applied to clinical settings recently, we aimed to review the results of genetic analysis, including NGS, and investigate the association with clinical characteristics in Korean PPGL patients.
Methods
We reviewed the medical records of PPGL patients who visited Severance hospital from 2006 to 2019. We documented the clinical phenotype of those who underwent targeted NGS or had known germline mutations of related genes.
Results
Among 57 PPGL patients, we found 28 pathogenic germline mutations of susceptibility genes. Before the targeted NGS was implemented, only obvious syndromic feature lead to the Sanger sequencing for the specific genes. Therefore, for the exact prevalence, only patients after the year 2017, when targeted NGS was added, were included (n=43). The positive germline mutations were found in 14 patients; thus, the incidence rate is 32.6%. Patients with germline mutations had a higher likelihood of family history. There were significant differences in the type of PPGLs, percentage of family history, metastasis rate, presence of other tumors, and biochemical profile among three molecular clusters: pseudohypoxic tricarboxylic acid cycle-related, pseudohypoxic von Hippel-Lindau (VHL)/endothelial PAS domain-containing protein 1-related, and kinase-signaling group. Germline mutations were identified in seven PPGL-related genes (SDHB, RET, VHL, NF1, MAX, SDHA, and SDHD).
Conclusion
We report the expected prevalence of germline mutations in Korean PPGL patients. NGS is a useful and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification is needed for precise management.

Citations

Citations to this article as recorded by  
  • Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma
    Susan Richter, Nicole Bechmann
    Journal of the Endocrine Society.2024;[Epub]     CrossRef
  • Main mechanisms and clinical implications of alterations in energy expenditure state among patients with pheochromocytoma and paraganglioma: A review
    Yuqi Yang, Tong Zhou, Xue Zhao, Yunjia Cai, Yao Xu, Xiaokun Gang, Guixia Wang
    Medicine.2024; 103(17): e37916.     CrossRef
  • Validation and Evaluation of 5 Scoring Systems for Predicting Metastatic Risk in Pheochromocytoma and Paraganglioma
    Qin Li, Zhigang Lan, Yong Jiang, Rui Wang, Ziyao Li, Xiaolin Jiang
    American Journal of Surgical Pathology.2024; 48(7): 855.     CrossRef
  • Differences between Patients with Sporadic and Familial Pheochromocytoma—Is It Possible to Avoid Genetic Testing in Certain Patients?
    María Consuelo Muñoz, Beatriz Febrero, Miriam Abellán, Antonio Miguel Hernández, José Manuel Rodríguez
    Biomedicines.2024; 12(6): 1352.     CrossRef
  • Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review
    Kwan Hoon Jo, Jaewoong Lee, Jaeeun Yoo, Hoon Seok Kim, Eun Sook Kim, Je Ho Han, Yi Sun Jang, Jae-Seung Yun, Jang Won Son, Soon Jib Yoo, Seung Hwan Lee, Dong Jun Lim, Hyuk-Sang Kwon, Seungok Lee, Sungdae Moon, Myungshin Kim
    Annals of Laboratory Medicine.2024; 44(6): 591.     CrossRef
  • Genotype and clinical phenotype characteristics of MAX germline mutation–associated pheochromocytoma/paraganglioma syndrome
    Bijun Lian, Jun Lu, Xudong Fang, Yiming Zhang, Wei Wang, Yi He, Hongyuan Yu, Feiping Li, Junwei Wang, Weiying Chen, Xiaoping Qi
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Novel and recurrent genetic variants of VHL, SDHB, and RET genes in Chinese pheochromocytoma and paraganglioma patients
    Chong Li, Jingyi Li, Chao Han, Ting Wang, Lixia Zhang, Zhifang Wang, Tingting Wang, Lijun Xu, Guangzhao Qi, Guijun Qin, Xialian Li, Lili Zheng
    Frontiers in Genetics.2023;[Epub]     CrossRef
  • Genetic Study in Pheochromocytoma: Is It Possible to Stratify the Risk of Hereditary Pheochromocytoma?
    Marta Araujo-Castro, César Mínguez Ojeda, Iñigo García Sanz, Maria Calatayud, Felicia Hanzu, Mireia Mora, Almudena Vicente, Concepción Blanco Carrera, Paz de Miguel Novoa, María del Carmen López García, Cristina Lamas, Laura Manjón-Miguélez, María del Cas
    Neuroendocrinology.2023; 113(6): 657.     CrossRef
  • The Role of VHL in the Development of von Hippel-Lindau Disease and Erythrocytosis
    Petra Hudler, Mojca Urbancic
    Genes.2022; 13(2): 362.     CrossRef
  • Bilateral Pheochromocytoma with Germline MAX Variant without Family History
    Shinnosuke Hata, Mai Asano, Hiroyuki Tominaga, Masahide Hamaguchi, Fumiya Hongo, Takeshi Usui, Eiichi Konishi, Michiaki Fukui
    Clinics and Practice.2022; 12(3): 299.     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
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  • Prevalence of Germline Variants in a Large Cohort of Japanese Patients with Pheochromocytoma and/or Paraganglioma
    Masato Yonamine, Koichiro Wasano, Yuichi Aita, Takehito Sugasawa, Katsutoshi Takahashi, Yasushi Kawakami, Hitoshi Shimano, Hiroyuki Nishiyama, Hisato Hara, Mitsuhide Naruse, Takahiro Okamoto, Tadashi Matsuda, Shinji Kosugi, Kazuhiko Horiguchi, Akiyo Tanab
    Cancers.2021; 13(16): 4014.     CrossRef
  • Recurrent Germline Mutations of CHEK2 as a New Susceptibility Gene in Patients with Pheochromocytomas and Paragangliomas
    Yinjie Gao, Chao Ling, Xiaosen Ma, Huiping Wang, Yunying Cui, Min Nie, Anli Tong, Dario De Biase
    International Journal of Endocrinology.2021; 2021: 1.     CrossRef
Close layer
Clinical Study
Epidemiology and Prognosis of Pheochromocytoma/Paraganglioma in Korea: A Nationwide Study Based on the National Health Insurance Service
Jung Hee Kim, Hyemi Moon, Junghyun Noh, Juneyoung Lee, Sin Gon Kim
Endocrinol Metab. 2020;35(1):157-164.   Published online March 19, 2020
DOI: https://doi.org/10.3803/EnM.2020.35.1.157
  • 8,569 View
  • 199 Download
  • 30 Web of Science
  • 27 Crossref
AbstractAbstract PDFPubReader   ePub   
Background

Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors originating from chromaffin cells. PPGLs are associated with a high mortality rate and several complications. To date, no epidemiological studies have been conducted on PPGLs in Asia. This study aimed to investigate the epidemiology and prognosis of PPGLs in Korea using nationwide data.

Methods

Using the National Health Insurance Service Database, subjects with a principal diagnosis of PPGLs on two or more occasions between 2003 and 2014 who satisfied the operational definition of PPGLs were included. Incidence, prevalence, complications, metastasis, and mortality were investigated.

Results

In total, 1048 subjects with a mean age of 47.6±16.1 years were included. There was no sex preponderance. The overall prevalence of PPGLs was 2.13 per 100,000 persons, and the overall age-standardized incidence rate was 0.18 per 100,000 person-years. Malignant PPGLs accounted for 17.7% (185 of 1,048) of cases, and 94 subjects exhibited metastasis at the time of diagnosis. Among initially non-metastatic PPGLs, 9.5% (nine of 954) eventually metastasized after a mean duration of 78.1±41.4 months. The 5-year survival rates for non-metastatic and metastatic PPGLs at diagnosis were 97% and 84%, respectively. Multivariable Cox regression models adjusted for covariates showed that metastatic PPGLs were associated with a 2.40-fold higher risk of mortality than non-metastatic PPGLs (95% confidence interval, 1.38 to 4.17; P=0.002).

Conclusion

PPGLs are rare in Korea, and the prognosis of these endocrine tumors varies depending on whether they are benign or malignant. This epidemiological study paves the way for further research on PPGLs.

Citations

Citations to this article as recorded by  
  • Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study
    Seung Shin Park, Chang Ho Ahn, Seunghoo Lee, Woochang Lee, Won Woong Kim, Yu‐Mi Lee, Su Jin Kim, Tae‐Yon Sung, Kyu Eun Lee, Jung Hee Kim, Seung Hun Lee, Jung‐Min Koh
    Journal of Internal Medicine.2024; 296(1): 68.     CrossRef
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    V.C. de Miguel, L.S. Aparicio, G. Sansó, A.L. Paissan, S.N. Lupi, S.H. Belli, J. Tkatch, M.J. Marín, M.B. Barontini
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    Wolfgang Raber, Raphael Schendl, Melisa Arikan, Andreas Scheuba, Peter Mazal, Valerie Stadlmann, Reinhard Lehner, Petra Zeitlhofer, Sabina Baumgartner-Parzer, Cornelia Gabler, Harald Esterbauer
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    Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
    Endocrinology and Metabolism.2023; 38(1): 10.     CrossRef
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    Sona Sharma, Lauren Fishbein
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    Andreas Kiriakopoulos, Periklis Giannakis, Evangelos Menenakos
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    Yang Yang, Jie Zhang, Liqun Fang, Xue Jia, Wensheng Zhang
    Drug Design, Development and Therapy.2022; Volume 16: 3599.     CrossRef
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    Andreas Ebbehoj, Kirstine Stochholm, Sarah Forslund Jacobsen, Christian Trolle, Peter Jepsen, Maciej Grzegorz Robaczyk, Åse Krogh Rasmussen, Ulla Feldt-Rasmussen, Reimar Wernich Thomsen, Esben Søndergaard, Per Løgstrup Poulsen
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Close layer
Case Reports
A Case of Calcitonin Secreting Pheochromocytoma.
Joo Won Byun, Young Goo Shin, Choon Hee Chung, Young Jun Won, Yoon Jong Choi, Eui Ryun Park, Mi Duck Lee, Chang Ho Song, Mi Youn Cho, Sung Jun Kang
J Korean Endocr Soc. 1996;11(3):343-347.   Published online November 7, 2019
  • 1,647 View
  • 32 Download
AbstractAbstract PDF
Pheochromocytoma is a catecholamine producing turnor and raise with less than 0.1% of hypertensive patients. It is developed, most commonly, in sporadic pheochromocytoma or multiple endocrine neoplasia type 2. Therefore, when hypercalcitoninemia is found in a patient with pheochromocytoma, the possibility of multiple endocrine neoplasia type 2 or the ectopic secretion of calcitonin must be considered. Recently we experienced a 45 year old male patient with sporadic pheochrornocytoma. He also had hypercalcitoninemia and normocalcemia. After the removal of pheochromocytoma, serum calcitnnin level returned to normal. Secretion of calcitonin was confirmed by immunohisto- chemical stain.
Close layer
Nerepinephrine Secreting Pheochromocytoma in the Organ of Zuckerkandl With Epinephrine Granules in Cytoplasm.
Eui Suk Kim, Gang Ryong Lee, Won Seok Lee, Jeong Aa Lee, Jie Jeong Jang, In Cheol Sunwoo, Dae Ha Kim, Gwang Seob Lee
J Korean Endocr Soc. 1996;11(2):233-239.   Published online November 7, 2019
  • 1,204 View
  • 18 Download
AbstractAbstract PDF
Extraadrenal pheochromocytomas developed from the paraganglia other than adrenal medulla are uncommon tumors. Such lesions have been reported that as much as 10% of retroperitoneal paragliomas arise outside the adrenal gland. But their incidence and prognosis are changing partly as a result of progression in developmental mechanism, diagnostic tools and concepts including ultrastructure, immunohistochemistry. The ultrastructure of chromaffine neoplasm from adrenal and extraadrenal tissues has been studied with chrarnaffine granule specificity and type of catecholamine content. With rare exceptions, extraadrenal chrornaffine tumor mainly has high concentration of norepinephrine which is suggested as dict relationship to numoruos electrone dense granular bodies in the cell cytoplasrn. High or intermediate level of epinephrine in tissue is associated with cytoplasmic granular bodies of much less density, Recently we experienced the exception, a case of norepinephrine secreting pheochrom-ocytoma in the organ of Zuckerkandl with epinephrine granules in cytoplasm and this discrepancy probably due to the plasticity - the differences in developmental process and local factors between adrenal medulla and extraadrenal tissues.
Close layer
A Case of Multiple Extraadrenal Pheochromocytoma Iocalized by 131 I-MIBG Scan.
Sung Hee Ihm, Jae Myung Yoo, Moon Gi Choi, Hyung Joon Yoo, Seok Boo Yoon, Jin Bong Kim, Doo Man Kim, Jin Seon Cho, Sang Kon Lee, Sung Woo Park
J Korean Endocr Soc. 1995;10(4):439-444.   Published online November 7, 2019
  • 1,368 View
  • 17 Download
AbstractAbstract PDF
Peroperative localization of pheochromocytoma is the very crucial step for the successful removal of tumors. Computed tomography(CT) and magnetic resonance(MR) imaging have been commonly used for tumor localization, but in some cases of pheochromocytoma, such as extraadrenal location or distant metastasis of malignant tumor, their localization is somewhat difficult. Recently ^131 I-metaiodobenzylguanidine(MIBG) scintigraphy has been developed and increasingly used for the localization of pheochromocytoma and reported to be more sensitive and specific than CT or MR imaging in the cases of extraadrenal tumor location.We report a case of multiple extraadrenal pheochromocytoma in which ^131 I-MIBG scintigraphy clearly localized two intraabdominal and one bladder tumors, after failure of localization with conventional CT and MR imaging.
Close layer
Original Article
Immunohistochemical Study of c - Myc, c - Fos and c - Jun Oncoprotein Expression in the Human Pheochromocytoma.
Jae Wha Jo, Eun Jig Lee, Moon Suk Nam, Kyung Rae Kim, Su Youn Nam, Young Duk Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh, Yong Hye Lee, Tae Seung Kim, Kwan Woo Lee
J Korean Endocr Soc. 1995;10(1):26-34.   Published online November 6, 2019
  • 1,251 View
  • 20 Download
AbstractAbstract PDF
A large number of studies for genes involved in oncogenesis have been done during last decade. Over 20 oncogenes have been isolated characterized, and the oncogene expressions in human tumors have been examined. The proto-oncogenes of c-Myc, c-Fos and c-Jun, which modulate the transcription factors, have overexpressed in a variety of human cancers. Immunohistochemical method was used in this study to examine c-Myc, c-Fos and c-Jun oncoprotein expression in 31 patients with human pheochromocytoma 28(90.0%) were benign and 3(10.0%) malignant. C-Myc oncoprotein immunoreactivity was found in 24 cases(77.4%), c-Fos in 29(93.5%), and c-Jun in 25(80.6%). Twenty-one(67.7%) showed positive immunoreactivity for all these oncoproteins, six(19.4%) for 2 oncoproteins, 3 for one oncoprotein. Only 1 case showed negative immunoreactivity for all 3 oncoproteins. The oncoprotein immunoreactivity did not correlate with the amount of 24 hour urinary catecholamine excretion. Although the number of malignant pheochromocytomsa was not so many, most of them showed that the immunoreactivity for oncoprotein was more than 30 percent of tumor cells.The expression of c-Myc, c-Fos and c-Jun oncoprotein were frequently found in human pheochromocytoma. These results suggest that the oncoprotein expression may play an important role in tumorogenesis and proliferation of human pheochromocytoma.
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Case Report
A Case of Pheochromocytoma Diagnosed as Preeclampsia during Prenancy.
Bong Yun Cha, Ho Young Son, Soon Jip Yoo, Ki Hyun Baik, Myung Hoon Kim, Moo Il Kang, E Jin Choi, Kwang Woo Lee, Sung Koo Kang, Uk Kim, Jong Man Won, Jin Young Yoo
J Korean Endocr Soc. 1994;10(3):295-299.   Published online November 6, 2019
  • 1,235 View
  • 29 Download
AbstractAbstract PDF
A case of a pregnant woman with an undiagnosed pheochromocytoma is presented. Gestational hypertension was developed at 33 weeks' gestation. Also she experienced intermittent chest discomfort, headache and irritability during those period. Normal vaginal delivery was successfully performed with close observation. Even though experiencing same symptoms for two years after delivery, she had been treated as neurosis. Uncatched pheochromocytoma was detected and the tumor was resected successfully. It seems to be that many cases of pheochromocytoma with pregnancy still go unrecognized because of close similarity between pheochromocytoma and toxemia. High index of suspicion should be maintained to achieve early diagnosis because antenatal diagnosis can lower the mortality in both mother and fetus.
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Original Article
A Clinical Observation of Endocrine Adrenal Tumors.
Hye Young Park, Tae Suk Kim, Soo Jin Lee, Dong Gu Choi, Moon Ho Kang
J Korean Endocr Soc. 1994;9(3):228-238.   Published online November 6, 2019
  • 1,215 View
  • 28 Download
AbstractAbstract PDF
Endocrine adrenal tumors are uncommon but clinically significant because they can be managed successfully by surgical therapy. During pregnancy, adrenal tumors can be a cause of death for both mother and baby, unless they diagnoses antenatally and managed properly. To investigate clinical characteristics of endocrine adrenal tumors, we analyzed 26 cases of adrenal tumor diagnosed and managed in Chung Ang Gil Hospital including cases associated with pregnancy and also a rare case of paraganglioma in liver. 1) There were 7 cases of Cushing's syndrome among which two cases were due to Cushing's disease and five cases were due to adrenal adenoma. Six cases were managed successfully by appropriate surgery. Another one case was associated with pregnancy but the patient expired due to sudden development of pulmonary edema and hypotension during preoperative preparation.2) Among 9 cases of primary aldosteronism, 8 cases were aldosterone-producing adenoma(APA) and 1 case was idiopathic hyperaldosteronism(IHA). In differential diagnosis between APA and IHA, diagnostic accuracy of postural study and adrenal CT was 86%, 78% respectively. In each one case of APA and IHA, adrenal venous aldosterone sampling was used for the differential diagnosis. Six cases of APA were managed by appropriate surgery. One patient with APA who refuses surgery and one patient with IHA were placed on spironolactone with good response.3) Among 10 cases of pheochromocytoma, seven cases were from adrenal gland and three cases were paragangliomas including one case originating from liver and two cases from abdominal ganglia. One patient with pheochromocytoma was diagnosed in 1st trimester of pregnancy and she was successfully treated by surgery.We observed 26 cases of endocrine adrenal tumors which were successfully managed except one case. We think that it is important to pay attention to adrenal tumor for early diagnosis particulary when associated with pregnancy. Paraganglioma in liver, although very rare, should be included in the differential diagnosis of space occupying lesion in liver.
Close layer
Namgok Lecture 2017
Adrenal gland
Bone Health in Adrenal Disorders
Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh
Endocrinol Metab. 2018;33(1):1-8.   Published online March 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.1.1
  • 5,985 View
  • 55 Download
  • 14 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   ePub   

Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

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Close layer
Review Article
Update on Modern Management of Pheochromocytoma and Paraganglioma
Jacques W. M. Lenders, Graeme Eisenhofer
Endocrinol Metab. 2017;32(2):152-161.   Published online June 23, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.2.152
  • 10,716 View
  • 344 Download
  • 100 Web of Science
  • 106 Crossref
AbstractAbstract PDFPubReader   ePub   

Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as 68Ga-DOTATATE (68Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace 123I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong.

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Close layer
Original Article
Clinical Study
A 5-Year Prospective Follow-Up Study of Lipid-Rich Adrenal Incidentalomas: No Tumor Growth or Development of Hormonal Hypersecretion
Camilla Schalin-Jäntti, Merja Raade, Esa Hämäläinen, Timo Sane
Endocrinol Metab. 2015;30(4):481-487.   Published online December 31, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.4.481
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AbstractAbstract PDFPubReader   
Background

Current guidelines for follow-up of adrenal incidentalomas are extensive and hampered by lack of follow-up studies. We tested the hypothesis that small lipid-rich adrenal incidentalomas, initially characterized by tumor size <40 mm and <10 Hounsfield units (HUs) on unenhanced computed tomography (CT) may not demonstrate excessive growth/hormonal hypersecretion on follow-up.

Methods

Sixty-nine incidentalomas in 56 patients were restudied with unenhanced CT and screening for hypercortisolism (dexamethasone suppression test [DST], plasma adrenocorticotropic hormone) and pheochromocytoma (24-hour urinary metanephrines and normetanephrines) 5 years later. Primary hyperaldosteronism was excluded at base-line.

Results

Tumor (n=69) size was similar before and after 5 years follow-up (19±6 mm vs. 20±7 mm). Mean tumor growth was 1±2 mm. Largest increase in tumor size was 8 mm, this tumor was surgically removed and histopathology confirmed cortical adenoma. DST was normal in 54 patients and two patients (3.6%) were still characterized by subclinical hypercortisolism. Initial tumor size was >20 mm for the patient with largest tumor growth and those with subclinical hypercortisolism. All patients had normal 24-hour urinary metanephrines and normetanephrines. Low attenuation (<10 HU) was demonstrated in 97% of 67 masses re-evaluated with unenhanced CT.

Conclusion

None of the patients developed clinically relevant tumor growth or new subclinical hypercortisolism. Biochemical screening for pheochromocytoma in incidentalomas demonstrating <10 HU on unenhanced CT is not needed. For such incidentalomas <40 mm, it seems sufficient to perform control CT and screen for hypercortisolism after 5 years.

Citations

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  • European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors
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