Pheochromocytoma

Last updated: November 7, 2022

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A pheochromocytoma is a catecholamine-secreting tumor that typically develops in the adrenal medulla. Pheochromocytomas are malignant in approximately 10% of cases. Excess sympathetic nervous system stimulation in individuals with pheochromocytoma leads to episodic blood pressure crises with paroxysmal headaches, diaphoresis, heart palpitations, and pallor. Pheochromocytomas may also be asymptomatic or manifest with persistent hypertension. Elevated catecholamine metabolites in the plasma or urine confirm the diagnosis, and imaging studies are used to determine the location of the tumor. Surgical resection is the treatment of choice. Preoperative alpha-adrenergic blockade (e.g., phenoxybenzamine) is indicated to prevent intraoperative complications such as hypertensive crises.

Pheochromocytomas and paragangliomas (PPGLs) may also be hormonally inactive in rare cases.

  • Incidence [3]
    • Most common tumor of the adrenal medulla in adults
    • Present in up to 1% of all hypertensive patients
  • Age: 3rd–5th decades of life [3]

Epidemiological data refers to the US, unless otherwise specified.

MAry P. sang “superCALi-fragilistic-EXpiali-DOcious” to the children 10 times: 10% of pheochromocytomas are MAlignant; 10% show CALcifications; 10% are EXtra-adrenal; 10% are DUal sided, i.e., bilateral; and 10% affect children.

Clinical presentation is related to fluctuating levels of excess epinephrine, norepinephrine, and dopamine secretion, so symptoms are characterized by patterns of relapse and remitting (episodic hyperadrenergic syndrome).

Patients can show typical clinical features (e.g., secondary hypertension) but may also be asymptomatic.

5 most important Problems (5 P’s) of Pheochromocytoma: increased blood Pressure, head Pain (headache), Perspiration, Palpitations, and Pallor

Hypertensive crises can be triggered by palpation of the tumor on abdominal exam.

Approach [1][6][7]

  • Consult a specialist early.
  • Obtain biochemical testing to prove catecholamine excess.
  • Obtain imaging to locate the tumor.
  • Consider indications for genetic testing on an individual basis.

Biochemical testing [1][2][6]

Screening for catecholamine excess [1]

Inconclusive test results should prompt further testing. False positives are common because of low pretest probability, suboptimal specificity, and the possibility of interfering factors.

Clonidine suppression test

  • Indication (not routinely recommended): inconclusive results from catecholamine excess testing
  • Method: normetanephrine is measured in plasma at baseline and 3 hours after oral administration of clonidine.
  • Interpretation
    • Inadequate normetanephrine suppression : Diagnosis is likely.
    • Adequate normetanephrine suppression : Diagnosis is unlikely. [1]

Imaging [1][2][6]

Obtain imaging studies only after catecholamine excess has been confirmed.

  • CT abdomen and pelvis with contrast: preferred initial modality
  • MRI: preferred in patients with known metastatic disease
  • Functional imaging studies: Consider in select patients under specialist consultation.

Additional diagnostics

Pheochromocytoma is often referred to as “the great mimic” because signs and symptoms are similar to those seen in many other clinical conditions. [10]

Endocrine

Adrenocortical carcinoma [11][12]

Other

Cardiovascular

Neurological

Miscellaneous

The differential diagnoses listed here are not exhaustive.

General principles [1][2][6]

Multidisciplinary care at a specialized center is recommended.

Treat hypertensive crisis due to pheochromocytoma with IV antihypertensives that target catecholamine excess (e.g., phentolamine, clevidipine, or nicardipine) and avoid beta blockers. [15][16][17]

Surgical resection [1][2][6]

A no-touch technique should be used because contact with the tumor can lead to massive catecholamine release.

Preoperative management [1][2][7]

Preoperative management of blood pressure and heart rate is required.

Treat PHEochromocytoma with PHEnoxybenzamine, but remember that Alpha blockers should be given Ahead and Beta blockers Behind.

Starting beta blockers before alpha blockers is contraindicated because doing so can cause life-threatening hypertensive crisis. Beta-blockers cancel out the vasodilatory effect of peripheral beta-2 adrenoceptors, potentially leading to unopposed alpha-adrenoceptor stimulation and thereby causing vasoconstriction and increased blood pressure.

Postoperative management [1][2][6]

  • Postoperative monitoring
  • Long-term monitoring
    • May include repeat biochemical testing and imaging studies; see “Diagnostics.”
    • The frequency of monitoring is based on individual risk for persistent, recurrent, and/or metastatic disease. [7]

The risk of postoperative acute adrenal insufficiency and subsequent hypoglycemia is especially high in individuals with bilateral adrenalectomy.

  1. Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet. 2005; 366 (9486): p.665-675. doi: 10.1016/s0140-6736(05)67139-5 . | Open in Read by QxMD
  2. Else T, Kim AC, Sabolch A, et al. Adrenocortical Carcinoma. Endocr Rev. 2013; 35 (2): p.282-326. doi: 10.1210/er.2013-1029 . | Open in Read by QxMD
  3. Adrenocortical Carcinoma - Patient Version. https://www.cancer.gov/types/adrenocortical. . Accessed: September 22, 2021.
  4. Sherlock M, Scarsbrook A, Abbas A, et al. Adrenal Incidentaloma. Endocr Rev. 2020; 41 (6): p.775-820. doi: 10.1210/endrev/bnaa008 . | Open in Read by QxMD
  5. Adrenal Gland Tumor: Statistics. https://www.cancer.net/cancer-types/adrenal-gland-tumor/statistics. . Accessed: September 22, 2021.
  6. Pheochromocytoma and Paraganglioma Treatment (PDQ®)–Health Professional Version. https://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq#link/_64_toc. Updated: July 10, 2015. Accessed: February 13, 2017.
  7. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  8. Zuber SM, Kantorovich V, Pacak K. Hypertension in Pheochromocytoma: Characteristics and Treatment. Endocrinol Metab Clin North Am. 2011; 40 (2): p.295-311. doi: 10.1016/j.ecl.2011.02.002 . | Open in Read by QxMD
  9. Lenders JWM, Duh QY, Eisenhofer G, et al. Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014; 99 (6): p.1915-1942. doi: 10.1210/jc.2014-1498 . | Open in Read by QxMD
  10. Chen H, Sippel RS, O’Dorisio MS, Vinik AI, Lloyd RV, Pacak K. The North American Neuroendocrine Tumor Society Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors: Pheochromocytoma, Paraganglioma & Medullary Thyroid Cancer. Pancreas. 2010; 39 (6): p.775-783. doi: 10.1097/mpa.0b013e3181ebb4f0 . | Open in Read by QxMD
  11. Fassnacht M, Assie G, Baudin E, et al. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020; 31 (11): p.1476-1490. doi: 10.1016/j.annonc.2020.08.2099 . | Open in Read by QxMD
  12. Neumann HPH, Young WF, Eng C. Pheochromocytoma and Paraganglioma. N Engl J Med. 2019; 381 (6): p.552-565. doi: 10.1056/nejmra1806651 . | Open in Read by QxMD
  13. Nölting S, Ullrich M, Pietzsch J, et al. Current Management of Pheochromocytoma/Paraganglioma: A Guide for the Practicing Clinician in the Era of Precision Medicine. Cancers. 2019; 11 (10): p.1505. doi: 10.3390/cancers11101505 . | Open in Read by QxMD
  14. Juhlin CC. Challenges in Paragangliomas and Pheochromocytomas: from Histology to Molecular Immunohistochemistry. Endocr Pathol. 2021; 32 (2): p.228-244. doi: 10.1007/s12022-021-09675-0 . | Open in Read by QxMD
  15. Whelton, PK, Carey, RM et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2017; 71 (6): p.e13–e115. doi: 10.1161/hyp.0000000000000065 . | Open in Read by QxMD
  16. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; 138 (17). doi: 10.1161/cir.0000000000000597 . | Open in Read by QxMD
  17. Peixoto AJ. Acute Severe Hypertension. N Engl J Med. 2019; 381 (19): p.1843-1852. doi: 10.1056/nejmcp1901117 . | Open in Read by QxMD

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