What is the diagnosis and treatment of Pheochromocytoma (adrenal gland tumor)?

From the Guidelines

Pheochromocytoma should be diagnosed and treated promptly to prevent morbidity and mortality, with the most recent guidelines recommending measurement of plasma free metanephrines as the best screening test, followed by surgical removal of the tumor after careful preoperative management with alpha-blockade and beta-blockade, as stated in the 2024 ESC guidelines 1. The diagnosis of pheochromocytoma typically involves biochemical testing, including measurement of metanephrines in blood or urine, which has a high sensitivity and specificity for the condition 1. Some key points to consider in the diagnosis and treatment of pheochromocytoma include:

• The condition is characterized by increased blood pressure variability, which constitutes an additional independent risk factor for cardiovascular morbidity and mortality 1
• The best screening test for pheochromocytoma is plasma free metanephrines, which carries a 99% sensitivity and an 89% specificity 1
• Surgical removal of the tumor is the definitive treatment, which requires careful preoperative management with alpha-blockade and beta-blockade to control blood pressure and prevent hypertensive crisis 1
• Genetic testing should be considered for all patients with pheochromocytoma, as about 40% have an associated hereditary syndrome such as MEN2, von Hippel-Lindau disease, or neurofibromatosis type 1 1
• The 2024 ESC guidelines recommend administering doxazosin or terazosin, followed by a beta-blocker, to control blood pressure and adrenergic crises, and adequate fluid administration should be carefully managed to prevent profound hypotension after tumor excision 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)

Pheochromocytoma treatment involves the use of medications such as:

• Phenoxybenzamine to control episodes of hypertension and sweating 2
• Metyrosine to reduce catecholamine biosynthesis, resulting in decreased endogenous levels of catecholamines 3 Key benefits of these medications include:
• Decreased frequency and severity of hypertensive attacks
• Decreased blood pressure
• Reduced catecholamine biosynthesis It is essential to note that beta-blocking agents may be necessary to use concomitantly with phenoxybenzamine if tachycardia is excessive 2

From the Research

Diagnosis and Treatment of Pheochromocytoma

• Pheochromocytoma is a rare tumor of the adrenal gland that can cause high blood pressure, tachycardia, and other symptoms 4.
• Diagnosis is typically made through measurement of plasma fractionated metanephrines or 24-h urinary fractionated metanephrines, with a clonidine test used if results are equivocal 4.
• Treatment typically involves preoperative treatment with α1-blockers, such as phenoxybenzamine or doxazosin, to control blood pressure and prevent hypertensive crises during surgery 5, 6, 4.

Preoperative Treatment with Phenoxybenzamine or Doxazosin

• Phenoxybenzamine has been traditionally used as the standard agent for alpha blockade before adrenalectomy for pheochromocytoma 5, 6.
• However, a recent study found that phenoxybenzamine is no longer the standard agent used for alpha blockade, with selective alpha blockers and calcium channel blockers being increasingly used due to reduced costs 7.
• Doxazosin has been shown to be a viable alternative to phenoxybenzamine, with fewer side effects such as orthostatic hypotension, oedema, and complaints of a stuffy nose 6.

Anesthetic Management and Perioperative Care

• Anesthetic management of pheochromocytoma patients requires careful control of blood pressure and heart rate, with the use of agents such as nitrous oxide, thiopental, narcotics, and enflurane 5.
• Perioperative care involves careful monitoring of hemodynamics and prompt control of hypertensive crises with sodium nitroprusside and arrhythmias with propranolol and lidocaine 5, 8.
• Continuous infusion of phentolamine has been used to control perioperative hypertensive episodes during surgical adrenalectomy 8.