Endocrinology and Metabolism

Review Article

Miscellaneous
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

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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.

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Editorial: Tumor metabolism and programmed cell death
Dan-Lan Pu, Qi-Nan Wu
Frontiers in Endocrinology.2024;[Epub] CrossRef

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

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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

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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

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

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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.

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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
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

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

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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

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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
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

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

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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

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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
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
Endocrinology and Metabolism.2021; 36(2): 322. CrossRef
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

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

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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.

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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

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Abstract 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.

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

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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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Addressing delays in the diagnosis of pheochromocytoma/paraganglioma
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Performance of plasma free metanephrines in diagnosis of pheochromocytomas and paragangliomas in the population of Asturias
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A Case of Sudden Death: Subarachnoid Hemorrhage, Pheochromocytoma, Berry Aneurysm
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Pheochromocytoma: A Genetic And Diagnostic Update
Leilani B. Mercado-Asis, Katherine I. Wolf, Ivana Jochmanova, David Taïeb
Endocrine Practice.2018; 24(1): 78. CrossRef
Retroperitoneal Paraganglioma Involving the Renal Hilum: A Case Report and Literature Review
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Case Reports

A Case of Retroperitoneal Paraganglioma Manifested as Intractable Constipation with Paralytic Ileus and Aggravated Hyperglycemia.: Seung Joon Hwang, Mi kwang Kwon, Suk Chon; J Korean Endocr Soc. 2008;23(6):450-455. Published online December 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.6.450

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Abstract PDF: Paragangliomas are extra-adrenal pheochromocytomas that arise from specialized neural crest cells. They are distributed anywhere from the upper neck to the pelvic floor, and they are classified on the basis of their anatomic origin. Functioning paragangliomas can cause the same clinical manifestations as pheochromocytoma, such as hypertension, diabetes mellitus, hyperadrenergic spells and so on. We experienced a retroperitoneal paraganglioma that was found in 66 year-old male who suffered from intractable constipation, and his constipation was caused by paralytic ileus and uncontrolled hyperglycemia. After he was diagnosed, removal of the paraganglioma was done and his clinical symptoms and sustained hyperglycemia were successfully resolved.

A case of Paraganglioma Arising in the Transverse Mesocolon.: Hong Il Kim, Bo kyung Koo, You Jin Lee, Jin Taek Kim, Young Min Cho, Kuhn Uk Lee, Seong Yeon Kim; J Korean Endocr Soc. 2005;20(5):496-501. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.496

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Abstract PDF

Herein, a case of a solitary primary paraganglioma arising in the mesentery, found in a hypertensive 70-year-old woman, who presented with nausea and postprandial abdominal discomfort, is reported. Ultrasonography and computed tomography showed a hypervascular mass abutting the second portion of the duodenum. An exploratory laparotomy revealed a 5.5 x 5.3 x 5cm sized mass in the mesentery of the transverse colon, which was histologically proven to be a paraganglioma. No intraoperative hemodynamic changes developed, and the postoperative course was uneventful. To our knowledge, this is the first case of a paraganglioma arising in the mesentery reported in Korea. Considering the unusual locations and the associated operative risk, it is necessary to rule out the possibility of a functioning paraganglioma in the preoperative differential diagnosis of an abdominal mass.

Citations

Citations to this article as recorded by

Mesenteric Lesions with Similar or Distinctive Appearances on CT
Hwajin Cha, Jiyoung Hwang, Seong Sook Hong, Eun Ji Lee, Hyun-joo Kim, Yun-Woo Chang
Journal of the Korean Society of Radiology.2019; 80(6): 1091. CrossRef

A Case of Fuctioning Extraadrenal Paraganglioma Mimicking Acute Coronary Syndrome.: Tae Hee Lee, Yeon Ah Lee, Tae Wook Woo, Gwan Pyo Koh, Cheol Young Park, Jung Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; J Korean Endocr Soc. 2003;18(1):94-99. Published online February 1, 2003

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Abstract PDF: A functioning paraganglioma is a rare catecholamine-producing tumor that arises from the extra-adrenal chromaffin tissue. Recently we experienced a case in which a 42 year-old male patient with a functioning extra-adrenal paraganglioma mimicked an acute coronary syndrome. A functioning extra-adrenal paraganglioma was diagnosed by means of a biochemical study and a radiological imaging study. After stabilizing his blood pressure, using alpha adrenergic blocker, we successfully removed a 6?cm sized paraganglioma from between the aorta and the IVC in the retroperitoneal space.

Original Article

Clinical Study of the Pheochromocytoma.: Dong Hyun Shin, Sin Gon Kim, Dong Rim Kim, Nan Hee Kim, Kyung Mook Choi, Saih Yun Baik, Dong Seop Choi, Sung Ock Suh; J Korean Endocr Soc. 2002;17(4):554-563. Published online August 1, 2002

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Abstract PDF: BACKGROUND
Pheochromocytoma may arise within the adrenal medulla, or in other locations where sympathetic ganglia or chromaffin tissues are known to exist. Approximately 0.1% of hypertensive patients have pheochromocytoma. Most of this hypertension can be cured by surgical removal of the tumor, but lethal complication can develop if proper treatment is not prepared. Therefore, accurate diagnosis and preoperative preparation is very important. The objective of this study was to evaluate the clinical characteristics of pheochromocytoma and the blood pressure change following tumor removal. METHOD: The medical records of 45 patients [29 cases of intra-adrenal, 16 cases of extra-adrenal (paraganglioma)] diagnosed with of pheochromocytoma at Korea University Medical Center between 1991 and 2001 were reviewed. RESULTS: Twenty of the cases were male and 25 were female. The mean age of these patients was 43 years old. Hypertension, headaches, palpitations and impaired glucose tolerance were observed more frequently in cases of intra-adrenal tumor than in those of extra-adrenal. In the extra-adrenal group, abdominal pain, hypertension and nausea were more frequently observed. A biochemical study showed that the sensitivity of the test for catecholamines and metabolites in 24 hours urine was over 80%. For the localization of tumors we used abdominal CT and MIBG. The sensitivities of the CT and MIBG for the tumor localization were 97 and 91%, respectively. Blood pressures during the operations were effectively controlled by preoperative treatment with phenoxybenzamine (non-competitive, non-selective -adrenoreceptor antagonists). CONCLUSION: Surgical treatment cured 23 of the 30 cases of hypertension with pheochromocytoma. We have to take careful approaches in the care of the patient who may have pheochromocytoma, due to the various clinical signs and symptoms.

Case Reports

A Case of Functioning Paraganglioma in Posterior Mediastinum.: Chang Hoon Choi, Sin Won Lee, Gui Hwa Jung, Si Hyung Park, Soon Hee Lee, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim, Sang Chul Lee, Eung Bae Lee, Tae In Park; J Korean Endocr Soc. 2002;17(2):292-296. Published online April 1, 2002

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Abstract PDF: Paraganglioma is an extraadrenal pheochromocytoma originating from chromaffin cells distributed in the sympathetic nervous systems. Functioning extraadrenal paragangliomas represent more than 10% of all pheochromocytomas, and seems to be highly malignant tumor in comparison to intraadrenal pheochromocytomas. Recently, we experienced a case of a paraganglioma in the posterior mediastinum. A 32-year-old woman was admitted to hospital due to dyspnea on exertion, and intractable hypertension. A chest X-ray showed a well-defined mass density on the right cardiac border, and biochemical studies showed characteristic findings of pheochromocytoma. A solitary pheochromocytoma was located in the posterior mediastinum using 131I-MIBG scintigraphy. The clinical manifestations, including hypertension and dyspnea were improved after operation.

A Case of Afrenocortical Carcinoma Associated with Multiple Paraganglioma.: Kyung Mook Choi, Jeong Heon Oh, Nan Hee Kim, Yong Hyun Kim, Ae Ree Kim, Chul Hwan Kim, Sang Jin Kim, Sei Hyun Baik, Dong Seop Choi; J Korean Endocr Soc. 1999;14(3):599-604. Published online January 1, 2001

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Abstract PDF: Simultaneous oceurrence of adrenocortical tumor and pheochromocytoma is extremely rare. Coexistence of adrenal tumor and pheochromocytoma was first reported by Cope in 1952 and some other cases were reported after that. But there was no report about coexistence of adrenocortical carcinoma and paragangliomas. Recently, we experienced a case of adrenocortical carcinoma associated with multiple paragangliomas. A 35-year-old woman was admitted to the hospital because of left upper abdominal pain. A palm-sized fum tender mass was palpated at left upper quadrant. Hormonal studies revealed pheochromocytomas feature. Fmergency operation was performed because of the possibility of intemal hemorrhage of the tumor. Operator found 10 cm sized mass in left adrenal area and also the other 5 small tumors adjacent to IVC. Pathologic report revealed that adrenal mass was adrenocortical carcinoma with hemorrhagic necrosis and tumors adjacent to IVC were paragangliomas. This patient was the first case of adrenocortical carcinoma with multiple paragangliomas in the world. So we report this case with a review of literature.

A Case of Atypical Retroperitonealk Paraganglioma: Fatal paroxysmal adrenergic crisis and geart failure after sonographically guided biopsy of unsuspected paraganglioma.: Sung Koo Kang, Jong Min Lee, Sung Ro Yoon, Seok Young Kim, Jin Sung Moon, Hye Soo Kim, Young Jae Lee, Hye Kyung Bae, Hye Kyung Lee, Hyun Kim; J Korean Endocr Soc. 1998;13(2):280-287. Published online January 1, 2001

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Abstract PDF: Paraganglioma is an extraadrenal pheochromocytoma originating from chromaffin ceIls distributed in sympathetic nervous systems. This tumor often can produce catecholamines and induce sustained or paroxysmal hypertension, with or without the typical symptams of headache, palpitation and sweating. Paraganglioma without the usual clinical manifestations is not easy to suspect and diagnose. Herein, we report a case of atypical retroperitoneal paraganglioma which was thought to be the pancreas tail mass and result in a paroxysmal adrenergic crisis and fatal dilated cardiomyopathy after the sonographically guided percutaneous biopsy. This rare case warns against the usual practice of percutaneous biopsy for the preoperative diagnosis of intraabdominal or retmperitoneal tumors.

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