What is the treatment for symptomatic Pheochromocytoma (adrenal gland tumor)?

From the Guidelines

The primary treatment for symptomatic pheochromocytoma is surgical removal of the tumor, but proper preoperative medical management with alpha-adrenergic blockade is essential to prevent life-threatening complications, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Preoperative Management

Before surgery, patients should undergo alpha-adrenergic blockade, typically with doxazosin or terazosin, followed by a beta-blocker, to control blood pressure and adrenergic crises 1.

• Alpha-blockers such as phenoxybenzamine, doxazosin, or terazosin should be started at least 7-14 days preoperatively with gradually increasing dosages until blood pressure targets are achieved 1.
• Beta-blockers like propranolol or metoprolol can be added to control tachycardia, but never before alpha blockade as this could worsen hypertension due to unopposed alpha-receptor stimulation 1.
• Calcium channel blockers such as amlodipine may be used as adjunctive therapy to control refractory hypertension or as presurgical monotherapy in cases of normal to mildly elevated blood pressure levels or cases of severe orthostatic hypotension 1.

Surgical Considerations

• Surgery should be performed by experienced surgeons, with careful intraoperative monitoring for blood pressure fluctuations 1.
• Patients with pheochromocytoma have peripheral hypovolaemia, which exposes them to the risk of profound hypotension, particularly right after tumour excision, and therefore, adequate fluid administration should be carefully managed 1.

Postoperative Care

• Postoperatively, patients require close monitoring for hypoglycemia and hypotension as catecholamine levels drop 1.
• Long-term follow-up is necessary to detect recurrence or metastatic disease, particularly in patients with genetic syndromes associated with pheochromocytoma 1.

From the FDA Drug Label

Phenoxybenzamine hydrochloride capsules are indicated in the treatment of pheochromocytoma, to control episodes of hypertension and sweating. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Metyrosine inhibits tyrosine hydroxylase, which catalyzes the first transformation in catecholamine biosynthesis, i. e. the conversion of tyrosine to dihydroxyphenylalanine (DOPA). Because the first step is also the rate-limiting step, blockade of tyrosine hydroxylase activity results in decreased endogenous levels of catecholamines, usually measured as decreased urinary excretion of catecholamines and their metabolites In patients with pheochromocytoma, who produce excessive amounts of norepinephrine and epinephrine, administration of one gram to four grams of metyrosine per day has reduced catecholamine biosynthesis from about 35% to 80% as measured by the total excretion of catecholamines and their metabolites (metanephrine and vanillylmandelic acid)

The treatment for symptomatic pheochromocytoma includes:

• Phenoxybenzamine to control episodes of hypertension and sweating, with possible concomitant use of a beta-blocking agent for excessive tachycardia 2
• Metyrosine to reduce catecholamine biosynthesis, resulting in decreased frequency and severity of hypertensive attacks 3

From the Research

Treatment Options for Symptomatic Pheochromocytoma

• The treatment of symptomatic pheochromocytoma typically involves preoperative treatment with an alpha-blocker, such as phenoxybenzamine or doxazosin, to prevent hemodynamic instability during surgery 4, 5.
• Phenoxybenzamine and doxazosin have been compared in several studies, with some showing that phenoxybenzamine may provide slightly better control of systolic arterial pressure, but at the cost of more pronounced postoperative hypotension 4, 5.
• The use of alpha-blockers is often accompanied by other vasoactive agents, such as beta-blockers, to control reflex tachycardia and additional antihypertensive medicines 4, 6.

Preoperative Management

• Preoperative management of pheochromocytoma involves a high index of clinical suspicion, biochemical confirmation of the diagnosis, preoperative localization, and pharmacologic treatment with alpha-adrenergic blockers and occasionally beta-adrenergic blockers 7.
• The goal of preoperative management is to stabilize the patient's blood pressure and prevent hemodynamic instability during surgery 7, 6.

Surgical Treatment

• Surgical treatment of pheochromocytoma involves meticulous anesthesia and intraoperative cardiovascular monitoring, as well as attention to surgical principles such as wide exposure, careful dissection, and complete exploration 7.
• Laparoscopic surgery is often used to treat pheochromocytoma, but may be converted to open surgery in some cases 8.

Outcomes and Prognosis

• The outcomes and prognosis for patients with symptomatic pheochromocytoma have improved in recent years, with surgery improving blood pressure and glycemic disturbances in both incidentaloma and symptomatic cases 8.
• However, recurrence and metastasis can still occur, and long-term follow-up is necessary to monitor for these complications 8.