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Recent Advances in Genetics, Diagnosis, Localization, and Treatment of Pheochromocytoma
Abstract
Pheochromocytoma is a rare but important tumor of chromaffin cells that is frequently considered in the evaluation of hypertension, arrhythmias, or panic disorder and in the follow-up of patients with particular genetic diseases. This report provides an update about the genetics, neurochemical diagnosis, localization by imaging, and surgical management of pheochromocytoma. Specific mutations of the RET proto-oncogene cause familial predisposition to pheochromocytoma in multiple endocrine neoplasia type II, and mutations in the von Hippel-Lindau tumor suppressor gene cause familial disposition to pheochromocytoma in von Hippel-Lindau disease. Recent findings demonstrating extraordinarily high sensitivity of plasma levels of metanephrines for detecting pheochromocytoma have led to an algorithm for clinical diagnostic steps. Nuclear imaging approaches, such as(123) I-metaiodobenzylguanidine scintigraphy and 6-[(18) F]fluorodopamine positron emission tomography, enhance both diagnosis and localization of the tumor, as described in an algorithm for patients with positive biochemical test results. Since pheochromocytoma is often benign, surgical resection by laparoscopic adrenalectomy can be curative. Areas requiring further work include determining appropriate follow-up of patients with familial pheochromocytoma, elucidating the bases for phenotypic differences, improving both specificity and sensitivity of biochemical tests, optimizing cost-effectiveness of diagnostic imaging, and testing the risk for tumor recurrence after partial adrenalectomy.
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“Pheochromocytoma may present incidentally, but on closer questioning, approximately 50% of cases have classical paroxysmal symptoms of sweating, headache, and tachycardia (189).”
From Adrenal incidentaloma (2020) · cites this paper as [189]
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Biochemical Diagnosis of Pheochromocytoma: Which Test Is Best?
Lenders, J. W. M., Pacak, K., Walther, M. M., Linehan, W. M., Mannelli, M., Friberg, P., Keiser, H. R., Goldstein, D. S., & Eisenhofer, G. (2002) · JAMA · doi:10.1001/jama.287.11.1427 · Cited by 1,134
Self-citationThe clinically inapparent adrenal mass: update in diagnosis and management
Mansmann, G., Lau, J., Balk, E., Rothberg, M., Miyachi, Y., & Bornstein, S. R. (2004) · Endocrine Reviews · doi:10.1210/er.2002-0031 · Cited by 781
Pheochromocytoma and Paraganglioma
Neumann, H. P. H., Young, W. F., & Eng, C. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1806651 · Cited by 736
The diagnosis and medical management of advanced neuroendocrine tumors.
Kaltsas, G. A., Besser, G. M., & Grossman, A. B. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0014 · Cited by 674
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Sherlock, M., Scarsbrook, A., Abbas, A., Fraser, S., Limumpornpetch, P., Dineen, R., & Stewart, P. M. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa008 · Cited by 347
“Screening for pheochromocytoma Pheochromocytoma may present incidentally, but on closer questioning, approximately 50% of cases have classical paroxysmal symptoms of sweating, headache, and tachycardia (189).”
BackgroundPheochromocytoma: The expanding genetic differential diagnosis.
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Manger, W. M., & Gifford, R. W. (2002) · The Journal of Clinical Hypertension · doi:10.1111/j.1524-6175.2002.01452.x · Cited by 143
Screening for Adrenal-Endocrine Hypertension: Overview of Accuracy and Cost-effectiveness
Schwartz, G. L. (2011) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2011.02.001 · Cited by 36
Yale, S. H., Vasudeva, S., Mazza, J. J., Rolak, L., Arrowood, J., Stichert, S., & Stratman, E. S. (2005) · Comprehensive Therapy · doi:10.1385/comp:31:1:059 · Cited by 11
Metadata
- Authors
- Pacak, K., Linehan, W. M., Eisenhofer, G., Walther, M. M., & Goldstein, D. S.
- Affiliations
- From the National Institutes of Health, Bethesda, Maryland.
- National Institutes of Health (US)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2001-02-20
- Volume
- 134
- Issue
- 4
- Pages
- 315-329
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2041573853
- Cited by
- 618
- References
- 134
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 13 · 2023: 9 · 2022: 20 · 2021: 21 · 2020: 19 · 2019: 19 · 2018: 22 · 2017: 13 · 2016: 9 · 2015: 24 · 2014: 27 · 2013: 29 · 2012: 19
- FWCI
- 32.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Oncology › Neuroblastoma Research and Treatments
- Keywords
- pheochromocytoma, RET proto-oncogene, multiple endocrine neoplasia type 2, von Hippel-Lindau disease, von Hippel-Lindau tumor suppressor gene, metanephrine, biochemical diagnosis, MIBG scintigraphy, tumor localization, laparoscopic adrenalectomy, familial pheochromocytoma, hypertension
- MeSH terms
- Proto-Oncogene Mas, Adrenal Gland Neoplasms, Algorithms, Biochemistry, Diagnostic Imaging, Humans, Pheochromocytoma, Sensitivity and Specificity
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