Endocrinology · Adrenal Disorders
The facts most likely to be tested
Press 1–5 to rate · ↑↓ to navigate
The classic clinical triad of episodic headache, diaphoresis, and tachycardia in a patient with paroxysmal hypertension is highly suggestive of pheochromocytoma.
Initial diagnostic screening should include measuring plasma free metanephrines or 24-hour urine fractionated metanephrines and catecholamines.
Imaging for localization of the tumor is performed with CT or MRI of the abdomen and pelvis only after biochemical confirmation of the diagnosis.
Preoperative management mandates the initiation of alpha-adrenergic blockade (e.g., phenoxybenzamine) at least 7–14 days prior to surgery to prevent hypertensive crisis.
Per the Endocrine Society (2014), beta-blockers should not be administered until adequate alpha-blockade is established to avoid unopposed alpha-adrenergic stimulation and subsequent life-threatening hypertension.
Pheochromocytoma is frequently associated with genetic syndromes, specifically MEN 2A and 2B, von Hippel-Lindau disease, Neurofibromatosis type 1, and hereditary paraganglioma-pheochromocytoma syndromes (SDHx mutations).
Definitive treatment for a localized pheochromocytoma is surgical resection following appropriate medical stabilization.
Vignette unlocked
A 34-year-old male presents to the clinic with a 3-month history of intermittent episodes of throbbing headaches, palpitations, and profuse sweating. He reports these episodes last approximately 20 minutes and are associated with a sense of impending doom. Physical examination reveals a blood pressure of 178/102 mmHg, which decreases to 135/85 mmHg after the episode resolves. He has a family history of medullary thyroid carcinoma in his mother. Laboratory studies show markedly elevated plasma free metanephrines, and CT of the abdomen shows a 4-cm left adrenal mass.
Which of the following is the most appropriate next step in management before surgical intervention?
Initiation of phenoxybenzamine
The patient presents with classic symptoms of pheochromocytoma, likely associated with MEN 2A. The most critical step before surgery is establishing alpha-blockade to prevent a hypertensive crisis during tumor manipulation.
Full handout
High yield triage
Etiology / Epidemiology
Catecholamine-secreting tumor of the adrenal medulla; up to 30-40% are hereditary, often associated with MEN 2A/2B, von Hippel-Lindau, Neurofibromatosis type 1, or SDHx mutations.
Clinical Manifestations
Classic triad of episodic headache, sweating, and tachycardia; suspect in patients with refractory hypertension.
Diagnosis
Initial screen with plasma free metanephrines or 24-hour urinary fractionated metanephrines; borderline results warrant repeat (supine) sampling or a clonidine suppression test (Endocrine Society 2014).
Treatment
Preoperative alpha-blockade (e.g., phenoxybenzamine) is recommended (Endocrine Society 2014); avoid initiating beta-blockers before alpha-blockade.
Prognosis
Surgical resection is usually curative; the classic 10% rule (10% metastatic, bilateral, extra-adrenal, pediatric) is a teaching mnemonic that underestimates the hereditary fraction (up to 30-40%).
Full handout
Epidemiology & Etiology
Most cases are sporadic, but roughly one-third (reported 25-40%) are linked to germline mutations in syndromes like MEN 2A/2B. The tumor arises from chromaffin cells of the adrenal medulla. The Endocrine Society (2014) recommends considering germline genetic testing for every patient, with highest yield in bilateral, extra-adrenal, young-onset, or familial cases.
Pertinent Anatomy
Tumors are primarily located in the adrenal medulla, but 10% arise from extra-adrenal sympathetic ganglia known as paragangliomas. These extra-adrenal sites include the Organ of Zuckerkandl near the aortic bifurcation.
Pathophysiology
Excessive secretion of epinephrine and norepinephrine leads to systemic vasoconstriction and cardiac stimulation. This results in paroxysmal hypertension, which can be triggered by anesthesia, exercise, or trauma. Chronic exposure leads to volume depletion due to persistent vasoconstriction.
Clinical Manifestations
Patients present with the classic triad: episodic headache, diaphoresis, and tachycardia. Hypertensive crisis is an uncommon but potentially fatal presentation, often precipitated by medications or surgery. Look for orthostatic hypotension due to chronic volume contraction. Do not palpate the abdomen as it may trigger a massive catecholamine release.
Diagnosis
The plasma fractionated metanephrines test is the most sensitive initial screening tool. Marked elevations (e.g., >3× the upper reference limit) are strongly suggestive; borderline results warrant repeat supine sampling or a clonidine suppression test. Once biochemical diagnosis is established, localize with CT or MRI of the abdomen/pelvis.
Treatment
Initiate phenoxybenzamine (non-selective alpha-blocker) 7-14 days prior to surgery to control blood pressure and expand intravascular volume. Beta-blockers (e.g., propranolol) should not be used first as they cause unopposed alpha-adrenergic vasoconstriction, leading to a hypertensive crisis. Surgical adrenalectomy is the definitive treatment.
Prognosis
Most patients achieve normotension post-resection, though some develop persistent hypertension. Long-term follow-up is recommended to monitor for recurrence or metastatic disease. Per the WHO classification, all pheochromocytomas have metastatic potential; metastatic disease is defined by the presence of metastases in non-chromaffin tissues.
Differential Diagnosis
Essential hypertension: lacks paroxysmal symptoms and elevated metanephrines
Hyperthyroidism: presents with tachycardia/sweating but lacks episodic hypertension
Carcinoid syndrome: associated with flushing and diarrhea, not paroxysmal hypertension
Panic disorder: mimics symptoms but lacks biochemical evidence of catecholamine excess
Cocaine/Amphetamine use: causes sympathetic surge; screen urine toxicology if suspected