Pheochromocytoma: Clinical sciences

A pheochromocytoma is a neuroendocrine tumor that develops from chromaffin cells. These cells are part of the sympathetic nervous system, so they secrete excessive catecholamines, such as norepinephrine and epinephrine, which causes severe hypertension.

The majority of pheochromocytomas develop in the adrenal gland; however, extra-adrenal pheochromocytomas, also called paragangliomas, can develop in other locations, such as the thorax, abdomen and pelvis.

Pheochromocytomas are commonly linked to genetic conditions like multiple endocrine neoplasia type 2, neurofibromatosis type 1, and Von Hippel-Lindau disease; but they can also occur sporadically in patients without a genetic condition.

Now, if your patient presents with chief concerns suggesting pheochromocytoma, you should first perform an ABCDE assessment to determine if they are unstable or stable.

If the patient is unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, provide supplemental oxygen.

Now here’s a high-yield fact! Patients with pheochromocytoma classically present with paroxysmal hypertension. When systolic blood pressure is above 180, or diastolic blood pressure is above 120 millimeters of mercury, that’s called a hypertensive crisis, which can lead to end-organ damage like heart failure, pulmonary edema, and intracranial hemorrhage.

So urgent treatment with an intravenous anti-hypertensive, such as nitroprusside, is essential. Keep in mind that blood pressure should be lowered gradually, over a 24-hour period, to avoid cerebral and myocardial hypoperfusion.

Alright, now that we're done with unstable patients, let’s go back to the ABCDE assessment and discuss the stable ones.

First, obtain a focused history and physical examination. Classically, patients with pheochromocytomas report episodes of severe hypertension associated with headaches, profuse sweating, and palpitations. They might also present with anxiety, chest pain, weakness, as well as nausea, and weight loss. Additionally, there might be a history of hypertension that has been unresponsive to antihypertensives.

On the flip side, physical exam findings typically include hypertension, which can be episodic or sustained, tachycardia, and orthostatic hypotension. Lastly, you may notice restlessness, tremor, and pallor. Of note, the physical exam in some patients can be normal outside hypertensive episodes.

Now, here’s a high-yield fact! The most common symptoms of pheochromocytoma can be remembered as the 5 Ps, which are increased blood Pressure; Pain, representing headache, Perspiration, Palpitations, and Pallor.

However, note that pheochromocytoma is known as the great masquerader, and it can present with isolated hypertension along with highly variable symptoms. So, always consider the possibility of pheochromocytoma in any patient with hypertension.

Alright, if you come across these findings, you should suspect pheochromocytoma.

Next, order labs, including 24 hour urine fractionated metanephrines or plasma free metanephrines. If metanephrines are not elevated, consider alternative diagnoses.

However, if metanephrines are elevated, proceed with imaging, such as a CT or MRI of the abdomen If imaging reveals no adrenal lesions, again, consider alternative diagnoses.

But, if imaging reveals a well-defined adrenal mass, you can diagnose pheochromocytoma.

Now here’s a clinical pearl to keep in mind! Pheochromocytomas follow the "rule of 10" where 10% are bilateral, so found in both adrenal glands; 10% occur in extra-adrenal areas; 10% are malignant, and 10% affect the pediatric population.

So, if metanephrine levels are elevated but no adrenal tumor is visible on the initial CT or MRI, consider imaging extra-adrenal locations. Also, note that you can use a PET scan to detect metastatic pheochromocytoma located in the lungs, liver, or bones.

Alright, now moving on to treatment!

The only treatment for pheochromocytoma is surgical removal, but preoperative management of hypertension is also important.

Typically, 10 to 14 days prior to surgery, you’ll start your patient on selective alpha 1 adrenergic blockers like prazosin, terazosin or doxazosin, or phenoxybenzamine.

Once you achieve adequate alpha-blockade, which usually takes around two days, you can start your patient on beta-blockers like metoprolol or propranolol to prevent reflex tachycardia.