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Pheochromocytoma and paraganglioma

Background

Overview

Definition
Pheochromocytomas and paragangliomas are rare NETs that originate from chromaffin cells in the adrenal medulla or extra-adrenal paraganglia, respectively.
1
Pathophysiology
The pathophysiology of these tumors involves the uncontrolled growth of chromaffin cells, which are responsible for the production of catecholamines. This overproduction can lead to a variety of symptoms and complications, including hypertensive crisis and CVD.
2
Epidemiology
The overall incidence of pheochromocytoma or paraganglioma in Canada is estimated to be 0.66 cases per 100,000 people per year.
3
Risk factors
Risk factors for pheochromocytoma and paraganglioma include certain genetic syndromes, such as MEN2, neurofibromatosis type 1, and von Hippel-Lindau syndrome. Additionally, mutations in the succinate dehydrogenase gene family have been found to predispose individuals to pheochromocytoma.
1
Disease course
Clinically, these tumors often present with symptoms related to catecholamine overproduction. These can include hypertension, palpitations, sweating, panic attacks, and pallor. Symptoms can be paroxysmal or persistent and may be triggered by certain medications, changes in abdominal pressure, or even micturition.
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Prognosis and risk of recurrence
The prognosis of these tumors is generally favorable if diagnosed early and managed appropriately. However, if left untreated or if diagnosis is delayed, these tumors can metastasize and lead to severe complications.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of pheochromocytoma and paraganglioma are prepared by our editorial team based on guidelines from the Canadian Urological Association (CUA 2023,2019), the American Association of Endocrine Surgeons (AAES 2022), the European Reference Network on Rare Adult Solid Cancers (EURACAN/ESMO 2020), the Canadian Hypertension Education Program (CHEP 2018,2016), the European Society of Endocrinology ...
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Screening and diagnosis

Indications for testing: as per AAES 2022 guidelines, test for pheochromocytoma in patients with:
adrenal incidentaloma with non-contrast adrenal CT findings of HU > 10
B
extra-adrenal malignancy with an indeterminate adrenal mass, even if it is likely to be a metastasis.
A
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Classification and risk stratification

Risk of malignancy: as per ESMO/EURACAN 2020 guidelines, define malignant pheochromocytoma or paraganglioma by the presence of metastasis, however, recognizing that all pheochromocytomas or paragangliomas have some malignant potential.
E

Diagnostic investigations

Clinical assessment: as per ESMO/EURACAN 2020 guidelines, obtain careful clinical assessment for signs of adrenal hormone excess in all patients with suspected pheochromocytoma.
E

More topics in this section

  • Metanephrine assays

  • Chromogranin A

  • Diagnostic imaging

  • Genetic testing

Diagnostic procedures

Biopsy: as per ESMO/EURACAN 2020 guidelines, do not perform biopsies of suspected pheochromocytoma or paraganglioma in most circumstances.
D

Perioperative care

Preoperative alpha-blockers: as per AAES 2022 guidelines, administer either selective or nonselective α-blockers, depending on the drug availability/cost, experience, and preference of the care team, to safely prepare patients for surgical resection of pheochromocytoma or paraganglioma. Recognize that selective α-blockers (doxazosin, prazosin, terazosin) are associated with more intraoperative hemodynamic instability while nonselective α-blockers (phenoxybenzamine) result in more postoperative hypotension, although there is no significant difference in morbidity or mortality between groups.
B

More topics in this section

  • Perioperative monitoring

Surgical interventions

Indications for adrenalectomy: as per CUA 2023 guidelines, perform adrenalectomy, with a minimally invasive technique when feasible, in patients with pheochromocytomas.
E

More topics in this section

  • Choice of surgical approach

  • Indications for debunking surgery

Specific circumstances

Patients with hereditary pheochromocytoma or paraganglioma: as per ES 2014 guidelines, individualize the management of hereditary pheochromocytoma or paraganglioma recognizing the distinct genotype-phenotype presentations.
B

Follow-up and surveillance

Indications for tertiary care referral: as per ESMO/EURACAN 2020 guidelines, refer all patients with suspected and proven pheochromocytoma or paraganglioma to be discussed in a multidisciplinary expert team meeting, at least at the time of initial diagnosis and in case of progressive disease.
E

More topics in this section

  • Follow-up (laboratory)

  • Follow-up (imaging)

  • Follow-up (duration)