Looking scared, Joan Ware, age 46, comes to the emergency department (ED) for the third time in the last 2 months. She says she just doesn’t understand what’s wrong; she’s always been healthy. Her symptoms, she says, begin suddenly with a headache, sweating, and palpitations. Then come the attacks in which she experiences severe fright, a feeling of doom, chest tightness, and light-headedness. The episodes are sporadic and distressing.
At her last ED visit, a physician referred her to a psychiatrist. She tried to explain that she wasn’t having anxiety attacks—and that she wasn’t crazy. Her blood pressure was 160/110, and her heart rate was 160 beats/minute. Her electrocardiogram showed sinus tachycardia. Her laboratory test results were normal.
What Ms. Ware doesn’t yet know is that she has a rare, lethal tumor called pheochromocytoma.
What is pheochromocytoma?
Pheochromocytoma is a tumor that comes from the chromaffin cells of the adrenal medulla and secretes catecholamines. Tumors can appear anywhere along the sympathetic chain, but 85% are in the adrenal gland. About 1 in 1,000 people with high blood pressure has a pheochromocytoma. The cause is unknown. Tumors may appear at any age, but most commonly, they appear in the fourth and fifth decades of life.
The secreted catecholamines may bind to:
• alpha-adrenergic receptors, causing vasoconstriction
• beta1-adrenergic receptors, causing inotropic effects
• beta2-adrenergic receptors, causing vasodilation.
Thus, norepinephrine-dominant pheochromocytomas increase systolic and diastolic blood pressure from alpha receptor stimulation, and epinephrine-secreting tumors can cause hypotension from beta2 stimulation.
Tumors can cause wild swings in blood pressure. In paroxysmal and sustained hypertension, blood pressure may be dangerously high. Such hypertension may result in target organ disease, such as left ventricular hypertrophy, retinopathy, encephalopathy, and proteinuria. Signs and symptoms typically occur weekly, but may occur several times a day or every few months.
Other signs and symptoms include headache, sweating, palpitations, chest pain, hot flashes, and psychological symptoms, such as anxiety, despair, and even aggression. Rarely, a pheochromocytoma is asymptomatic. Complications of pheochromocytomas include pulmonary edema, cardiac arrhythmias, myocarditis, dilated congestive cardiomyopathy, cerebral vascular accidents, and renal failure. Without effective treatment, the complications will almost inevitably be fatal.
Uncovering diagnostic clues
On Ms. Ware’s third visit to the ED, a nurse’s careful history began with this open-ended statement, “Tell me your story.” As the patient spoke, the nurse considered how the signs and symptoms were connected. Then, she remembered that years ago, she had a patient with similar signs and symptoms, who was diagnosed with a pheochromocytoma.
Ms. Ware’s story provided many clues, including the fact that her signs and symptoms were precipitated by exertion and anxiety. As the nurse knew, pheochromocytoma attacks can also be triggered by foods containing tyramine, certain drugs, abdominal pressure, trauma, pain, anesthesia, intubation, chemotherapy, bladder distention, and micturition. Her knowledge, willingness to listen to the patient, detective work, and astute clinical decision making led her to the possibility that Ms. Ware had a pheochromocytoma.
The nurse discussed her suspicions with the physician, who then ordered a 24-hour urine collection. After Ms. Ware’s blood pressure was stabilized with an alpha blocker, she left the ED with a big plastic urine jug and the hope that she would find out what was happening to her.
Zeroing in on pheochromocytoma
Diagnosing a pheochromocytoma requires measuring plasma-free meta-nephrine and catecholamine levels and analyzing a 24-hour urine specimen for fractionated metanephrine, catecholamines, total metanephrine, and vanillymandelic acid levels. The first two urine tests have good sensitivity; the latter two have good specificity.
Analysis of Ms. Ware’s 24-hour urine specimen revealed excessive catecholamine levels. The next step was to find the tumor, so the physician ordered magnetic resonance imaging (MRI) of her abdomen, and the radiologist ordered whole-body scintigraphy using metaiodobenzylguanidine (MIBG). The MRI revealed a mass on her left adrenal gland, and the MIBG confirmed that it was a pheochromocytoma and revealed no extra-adrenal tumors.
Ms. Ware’s physician told her that the tumor could be removed surgically and explained that surgery is the preferred treatment. Without it, the tumor could cause dangerous complications down the road.
For 10 days before surgery, Ms. Ware took a selective postsynaptic alpha1 blocker to reduce her blood pressure and prevent intraoperative hypertensive crises. The 10-day course allows the blood volume to expand. A non-selective alpha blocker such as phenoxybenzamine (Dibenzyline) may be prescribed to normalize blood pressure, but this type of drug can cause orthostatic hypotension and reflex tachycardia and may increase postsurgical complications. Selective postsynaptic alpha1 blockers eliminate these problems. Also to expand volume, Ms. Ware added a liberal amount of salt to her diet, as instructed by her nurse.
Surgical removal of a pheochromocytoma is a high-risk procedure. During surgery, the patient’s heart rhythm and vital signs are monitored, using an arterial line. Hypertensive episodes during surgery are treated with an I.V. infusion of phentolamine (Regitine) or nitroprusside (Nipride). Lidocaine or esmolol (Brevibloc) are used for cardiac arrhythmias.
Today, most tumors are removed laparoscopically, unless they are large, or there are lots of them. In Ms. Ware’s case, the surgeon was able to perform a laparoscopic adrenalectomy, which is less invasive and thus poses less risk than other procedures. Fortunately, her tumor was well defined, and the surgeon said it was benign.
Providing postoperative care
After surgery, your patient is at risk for hypotension from venous dilation caused by the sudden withdrawal of catecholamines, diminished receptor sensitivity to catecholamines, and the alpha blocker therapy. A postoperative hypotensive patient may need I.V. fluids, colloids, and vasopressors.
Because pheochromocytomas are highly vascular tumors, surgery causes significant blood loss and hypo-volemia. By the time the patient is discharged, blood pressure usually has returned to normal. In Ms. Ware’s case, the surgeon successfully removed the tumor, and she didn’t have a hypertensive crisis during surgery or hypotension after it.
One to two weeks after surgery, a patient has follow-up biochemical assays to ensure that all catecholamine-producing tumor cells have been removed. Complete surgical resection of a benign pheochromocytoma usually means a normal life expectancy.
Following up with genetic counseling
For some types of pheochromocytoma, care includes genetic counseling. Between 20% and 30% of pheochromocytomas are familial and tend to be associated with other familial diseases, such as multiple endocrine neoplasia type 2a, von Hippel-Lindau disease, and neurofibromatosis.
Some 10% to 50% of extra-adrenal tumors, called paragangliomas, are inherited and more common in children than in adults. These tumors lie near sympathetic and parasympathetic ganglia in the abdomen and pelvis and occasionally in the chest or neck. About one-half of paragangliomas are malignant. Be sure to encourage any patient with a paraganglioma to follow the genetic counseling protocol.
Meeting the patient’s needs
A diagnosis of pheochromocytoma can be a relief to your patient, but facing surgery can still be frightening. Expect questions about whether the tumor will come back, how it got there in the first place, and whether or not it can be passed on to others.
Of course, the first thing a patient with a pheochromocytoma needs is a clinician who thinks beyond the usual causes of common signs and symptoms. Because of such thinking, Ms. Ware is doing well today and hasn’t had any frightening episodes since her surgery.
Despite all the technological advances in health care, saving a patient like Ms. Ware depends mainly on imaginative clinical decision making that leads to an accurate diagnosis and treatment for a deadly condition.
Katharyn F. Daub is Associate Professor and Chair at the University of Hawaii at Hilo.