Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (751 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A usually benign, well-encapsulated, lobular, vascular tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. During severe attacks, there may be headache; sweating, palpitation, apprehension, tremor; pallor or flushing of the face, nausea and vomiting, pain in the chest and abdomen, and paresthesias of the extremities. The incidence of malignancy is as low as 5% but the pathologic distinction between benign and malignant pheochromocytomas is not clear. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles and Practice of Oncology, 3d ed, p1298)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Pheochromocytomas; Pheochromocytoma, Extra-Adrenal; Extra-Adrenal Pheochromocytoma; Extra-Adrenal Pheochromocytomas; Pheochromocytoma, Extra Adrenal; Pheochromocytomas, Extra-Adrenal.
Where it fits in the MeSH classification
- Broader topics
- Paraganglioma
- See also
- Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b
Related concepts
- Adrenal Medulla
- Epinephrine
- Norepinephrine
- Hypertension
- Headache
- Sweating
- Tremor
- Pallor
- Flushing
- Nausea
Research landscape
PubMed indexes 17,529 records tagged with the MeSH heading “Pheochromocytoma” (counts retrieved 2026-10-29). 1,833 of them (10.5%) were published from 2020 onward, and the busiest period so far is through 1999 with 10,152 records.
Reviews account for 2,193 records (12.5%) and meta-analyses for 50. Randomized controlled trials number 26 (0.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 10,152 |
| 2000-2009 | 2,831 |
| 2010-2019 | 2,713 |
| 2020 onward | 1,833 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,193 | 12.5% |
| Meta-analyses | 50 | 0.3% |
| Randomized controlled trials | 26 | 0.1% |
Method: PubMed query "Pheochromocytoma"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in cancer and oncology
Cancer research spans very different kinds of evidence. Laboratory studies in cell lines and animal models reveal mechanisms but often do not translate to patients. Early-phase trials mainly test safety and dosing, while phase 3 randomized trials and their meta-analyses are the usual basis for treatment conclusions. Outcomes also differ in meaning: tumour shrinkage, progression-free survival and overall survival are not interchangeable, and screening studies can be distorted by lead-time and overdiagnosis. When reading a result, check the cancer type and stage studied, the comparison treatment, and which outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma | 2023 | Research article Design not recorded in structured metadata | 78 | cc by PMID 36854674 · DOI · PMC9975198 |
| Imaging of Pheochromocytomas and Paragangliomas | 2024 | Review article Design not recorded in structured metadata | 71 | cc by PMID 38206185 · DOI · PMC11074798 |
| Silent pheochromocytoma and paraganglioma: Systematic review and proposed definitions for standardized terminology | 2022 | Systematic review Design not recorded in structured metadata | 57 | cc by PMID 36325453 · DOI · PMC9618947 |
| Functional characterization of SDHB variants clarifies hereditary pheochromocytoma and paraganglioma risk and genotype-phenotype relationships | 2026 | Research article Design not recorded in structured metadata | 8 | cc by PMID 41252211 · DOI · PMC12904712 |
Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL).
- Closing excerpt
- Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (147 words)
The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36854674 · DOI · PMC9975198
Imaging of Pheochromocytomas and Paragangliomas [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic.
- Closing excerpt
- We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (248 words)
Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38206185 · DOI · PMC11074798
Silent pheochromocytoma and paraganglioma: Systematic review and proposed definitions for standardized terminology [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes.
- Closing excerpt
- In the present analysis we provide an overview of the literature and propose standardized terminology in an attempt at harmonization to facilitate scientific communication.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (182 words)
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPGL due to a hereditary background or a previous tumor is leading to the diagnosis of these tumors at an early stage. This has resulted in an increasing use of the term "silent" PPGL. This term and other variants are now commonly found in the literature without any clear or unified definition. Among the various terms, "clinically silent" is often used to describe the lack of signs and symptoms associated with catecholamine excess. Confusion arises when these and other terms are used to define the tumors according to their ability to synthesize and/or release catecholamines in relation to biochemical test results. In such cases the term "silent" and other variants are often inappropriately and misleadingly used. In the present analysis we provide an overview of the literature and propose standardized terminology in an attempt at harmonization to facilitate scientific communication.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36325453 · DOI · PMC9618947
Functional characterization of SDHB variants clarifies hereditary pheochromocytoma and paraganglioma risk and genotype-phenotype relationships [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Hereditary pheochromocytoma and paraganglioma (hPPGL) is caused by pathogenic mutations in succinate dehydrogenase (SDH) genes, commonly SDHB.
- Closing excerpt
- Functional characterization of SDHB missense variants supports clinical classification, informs hPPGL risk stratification, and has immediate diagnostic impact.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (174 words)
Hereditary pheochromocytoma and paraganglioma (hPPGL) is caused by pathogenic mutations in succinate dehydrogenase (SDH) genes, commonly SDHB. However, over 80% of SDHB missense variants are classified as variants of uncertain significance (VUS), limiting clinical interpretation and diagnostic utility of germline testing. To provide functional evidence of SDHB allele pathogenicity or benignity, we developed a cellular complementation assay that quantifies intracellular succinate/fumarate ratios as a readout of SDH enzymatic activity. This assay reliably distinguished pathogenic from benign alleles with high fidelity, outperforming and complementing computational predictions. Functional assessment of patient-derived VUS alleles supported reclassification of 87% of tested variants and revealed that mutations in the iron-sulfur cluster domain were amorphic, while those at or beyond the C-terminal residue Tyr273 retained function. Variants associated with Leigh syndrome retained activity, consistent with their biallelic inheritance and distinct pathogenic mechanisms from SDHB-related tumorigenesis. Notably, hypomorphic pathogenic SDHB variants correlated with increased head and neck paraganglioma occurrence, revealing a genotype-phenotype relationship. Functional characterization of SDHB missense variants supports clinical classification, informs hPPGL risk stratification, and has immediate diagnostic impact.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41252211 · DOI · PMC12904712
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Pheochromocytoma and Paraganglioma [5]
- Research article Overview of the 2022 WHO Classification of Paragangliomas and Pheochromocytomas [6]
- Research article European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma [7]
- Research article Personalized Management of Pheochromocytoma and Paraganglioma [8]
- Research article Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up [9]
- Research article Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension [10]
References
- Calsina B, Piñeiro-Yáñez E, Martínez-Montes ÁM, Caleiras E, Fernández-Sanromán Á, Monteagudo M, et al.. Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma. . 2023. PMID 36854674 · DOI · PMC9975198
- Timmers HJLM, Taïeb D, Pacak K, Lenders JWM. Imaging of Pheochromocytomas and Paragangliomas. . 2024. PMID 38206185 · DOI · PMC11074798
- Constantinescu G, Preda C, Constantinescu V, Siepmann T, Bornstein SR, Lenders JWM, et al.. Silent pheochromocytoma and paraganglioma: Systematic review and proposed definitions for standardized terminology. . 2022. PMID 36325453 · DOI · PMC9618947
- Lee S, Needleman L, Park J, Schugar RC, Guo Q, Ford JM, et al.. Functional characterization of SDHB variants clarifies hereditary pheochromocytoma and paraganglioma risk and genotype-phenotype relationships. . 2026. PMID 41252211 · DOI · PMC12904712
- Neumann HPH, Young WF, Eng C. Pheochromocytoma and Paraganglioma. N Engl J Med. 2019. PMID 31390501 · DOI
- Mete O, Asa SL, Gill AJ, Kimura N, de Krijger RR, Tischler A. Overview of the 2022 WHO Classification of Paragangliomas and Pheochromocytomas. Endocr Pathol. 2022. PMID 35285002 · DOI
- Plouin PF, Amar L, Dekkers OM, Fassnacht M, Gimenez-Roqueplo AP, Lenders JW, et al.. European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. Eur J Endocrinol. 2016. PMID 27048283 · DOI
- Nölting S, Bechmann N, Taieb D, Beuschlein F, Fassnacht M, Kroiss M, et al.. Personalized Management of Pheochromocytoma and Paraganglioma. Endocr Rev. 2022. PMID 34147030 · DOI · PMC8905338
- Fassnacht M, Assie G, Baudin E, Eisenhofer G, de la Fouchardiere C, Haak HR, et al.. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020. PMID 32861807 · DOI
- Lenders JWM, Kerstens MN, Amar L, Prejbisz A, Robledo M, Taieb D, et al.. Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2020. PMID 32412940 · DOI · PMC7486815
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.