Pheochromocytoma is a rare neuroendocrine tumour arising from catecholamine-producing chromaffin cells of the adrenal medulla. Approximately 15–20% of these tumours originate outside the adrenal glands (extra-adrenal), where they are commonly referred to as paragangliomas. Pheochromocytomas secrete excessive amounts of catecholamines, predominantly norepinephrine and epinephrine, resulting in episodic or sustained hypertension and a variety of cardiovascular and systemic manifestations. Although uncommon, pheochromocytoma is a potentially life-threatening but curable cause of secondary hypertension when diagnosed early and managed appropriately.

Pathophysiology

Pheochromocytomas produce excessive catecholamines independent of normal physiological regulation. Excess norepinephrine and epinephrine stimulate α- and β-adrenergic receptors, leading to systemic vasoconstriction, increased cardiac output, tachycardia, and metabolic disturbances. Catecholamine release is often episodic, producing recurrent hypertensive crises and characteristic paroxysmal symptoms. Persistent catecholamine excess may lead to cardiovascular complications, including arrhythmias, cardiomyopathy, myocardial infarction, stroke, and multiorgan dysfunction.

Risk factors

• Hereditary endocrine syndromes (e.g., Multiple Endocrine Neoplasia type 2)

• Von Hippel–Lindau syndrome

• Neurofibromatosis type 1

• SDHx gene mutations

• Family history of pheochromocytoma or paraganglioma

• Previous history of adrenal tumours

Clinical presentation

The clinical manifestations result from episodic or continuous release of excess catecholamines into the circulation.

Typical symptoms include:

• Headache

• Palpitations

• Anxiety

• Excessive sweating (diaphoresis)

• Hypertension, which may be:

  • Paroxysmal (approximately 48%)

  • Persistent (approximately 29%)

Other manifestations may include:

• Tremor

• Pallor

• Tachycardia

• Chest pain

• Weight loss

• Heat intolerance

• Orthostatic hypotension

• Hyperglycaemia

Diagnostic criteria

The diagnosis requires biochemical confirmation of catecholamine excess before tumour localization.

Clinical suspicion should be raised in patients with:

• Episodic headaches

• Palpitations

• Diaphoresis

• Hypertension, particularly when paroxysmal or resistant to treatment

Investigations

Biochemical investigations

Tumour localization

Tumour localization should only be performed after biochemical confirmation of catecholamine excess.

• Approximately 85% of catecholamine-secreting tumours are located in the adrenal glands.

• Approximately 95% are located within the abdomen and pelvis.

• CT scan or MRI are effective imaging modalities for tumour localization.

  • CT sensitivity: approximately 89%

  • MRI sensitivity: approximately 98%

Management

The definitive treatment of pheochromocytoma is complete surgical removal of the tumour. However, preoperative medical preparation is essential to reduce the effects of excessive catecholamines and minimize perioperative complications.

Non-pharmacological management

• Complete surgical resection is the definitive treatment.

• Ensure biochemical diagnosis before imaging and surgery.

• Adequate preoperative preparation is mandatory.

• Careful intraoperative and postoperative haemodynamic monitoring is recommended.

• Long-term follow-up is required because recurrence may occur, particularly in hereditary disease.

Pharmacological management

Before planned surgery, excess catecholamine effects should be controlled using α-adrenergic blockade.

Non-selective α-adrenergic antagonist

• Phenoxybenzamine (PO) 10 mg every 12 hours initially, gradually increasing to 20–40 mg every 8–12 hours according to blood pressure response and tolerability.

OR

Selective α₁-adrenergic antagonist

• Doxazosin (PO) 1–2 mg once daily.

Combined α- and β-adrenergic blockade may be required in selected patients after adequate α-blockade has been established to control persistent tachycardia. β-blockers should never be started before adequate α-blockade, as unopposed α-adrenergic stimulation may precipitate severe hypertensive crisis.

Prognosis

The prognosis is excellent when pheochromocytoma is diagnosed early and completely resected surgically. Appropriate preoperative α-adrenergic blockade substantially reduces perioperative morbidity and mortality. Untreated disease may lead to life-threatening complications including hypertensive emergencies, cardiac arrhythmias, myocardial infarction, stroke, heart failure, and sudden death. Lifelong follow-up is recommended, especially in patients with hereditary syndromes, bilateral tumours, or extra-adrenal disease because recurrence or metastatic disease may occur.