Pheochromocytoma Case File

Pheochromocytoma Case File

Lydia Conlay, MD, PhD, MBA, Julia Pollock, MD, Mary Ann Vann, MD, Sheela Pai, MD, Eugene C. Toy, MD

Case 42

A 52-year-old man presents with severe hypertension, exceptionally severe headaches, and diaphoresis. He is found to have an adrenal mass on imaging and is referred to a surgeon for excision. Before proceeding with surgery, the patient is referred to the preoperative anesthesia clinic for evaluation and management of his hypertension. He is otherwise healthy, and until the past several months, exercised regularly, and did his own yard work. His exercise tolerance has recently decreased. He has had no chest pain, no shortness of breath, but does have occasional palpitations which he states he has had for a very long time. He has not noticed any issues with mentation, speech, movement, vision, or seizure activity. The patient is quite anxious, and because of the severity of the headaches, is worried about the possibility of an intracranial aneurysm. His review of systems is otherwise negative.

The patient’s family history is remarkable in that it is unremarkable. His father is 95 years old, and in good health with some signs of a senile dementia. His mother died many years ago in an automobile accident. Neither his parents nor siblings have had any problems with cardiovascular diseases, nor have experienced any type of endocrinologic problems. On physical examination, the patient’s blood pressure is 220/115 mm Hg, HR 87 beats/minute, and respirations are 15 breaths/minute. He is 70 in. tall and weighs 62 kg. His physical examination is unremarkable, as is his routine blood chemistry panel. An ECG shows left ventricular hypertrophy. The patient is scheduled for surgery for his condition. Urine catecholamines are elevated.

➤ What other preoperative tests should be done?

➤ What medications would help with blood pressure control preoperatively in this patient?

➤ What are the likely complications following surgery?

ANSWERS TO CASE 42:

Pheochromocytoma

Summary: A healthy, 52-year-old man presents with hypertension, headaches, diaphoresis, recently reduced exercise tolerance, and anxiety. An adrenal mass is discovered on imaging and scheduled for excision.

➤ Preoperative tests: Echocardiogram and cardiac stress test. In patients with evidence suggesting myocardial dysfunction, it is advisable to obtain a preoperative echocardiogram to evaluate left ventricle function. Similarly, a stress test is useful to delineate the extent of coronary artery disease, if any. In addition to the left ventricular hypertrophy seen on his ECG, pheochromocytoma can also be associated with cardiomyopathy. After initiation of alpha-receptor blockade, left ventricular function often improves dramatically. Severe, uncontrollable, intraoperative hypertension and worse outcome may result if the patient is not adequately prepared preoperatively.

➤ Preoperative management: Adrenergic receptor blockade is the hallmark of preoperative management for patients with pheochromocytomas. Alphareceptor blockade has classically been achieved with phenoxybenzamine (nonselective alpha-1 and alpha-2 antagonist). Terazosin, prazosin, or doxazosin (selective alpha-1 blockers) may be preferable, since their half-lives are significantly shorter than phenoxybenzamine’s, making persistent postoperative hypotension less likely.

➤ Complications following surgery: Following removal of a catecholaminesecreting tumor, there can be persistent postoperative hypotension. The hypotension is thought to be secondary to hypovolemia or a sluggish recovery of the vasoconstrictor mechanisms following the withdrawal of catecholamines secreted by the tumor. Generally, this type of hypotension is responsive to fluid resuscitation. Astute anesthesiologists plan ahead, and begin volume replacement (at least 1000 mL) prior to clamping of the tumor’s venous drainage. It is always appropriate to consider postoperative bleeding as a possibility if postoperative hypotension is not responsive to adequate volume resuscitation.

ANALYSIS

Objectives

1. Become familiar with the issues encountered in the preoperative evaluation of a patient with pheochromocytoma.

2. Review the physiology and treatment of pheochromocytoma.

3. Understand the differential diagnosis of intraoperative hypertension.

Considerations

This patient presents with the classic signs of a pheochromocytoma: hypertension, headaches, diaphoresis, a reduced exercise tolerance, and anxiety. His decreasing exercise tolerance is suggestive of left ventricular dysfunction, particularly since he was otherwise healthy. About 10% of pheochromocytomas are of metastatic origin which could also account for the change in his exercise tolerance, but this would not obviate the need to examine his left ventricular function.

The patient is monitored closely in the days leading up to his surgical procedure. His blood pressure is well controlled, he is no longer having and PVCs, he has no ST-T wave changes on his ECG, and he does indeed have orthostatic hypotension. Nevertheless, the need for invasive monitoring is essential. Nicardipine is prepared for administration by bolus and by infusion, and nitroglycerine is in the room and ready if needed. Conversely, a phenylephrine infusion is prepared to treat hypotension, should it occur. Once the patient is brought to the operating room, a large-bore intravenous and an arterial line are placed. Approximately 500 mL of normal saline are administered to assure normovolemia. Since this is a laparoscopic procedure (and CO2 insufflation affects CVP), central venous access is not obtained. Since this patient has noticed a decline in his exercise tolerance, etomidate is administered as an induction agent. A large dose of the opiate fentanyl is administered just prior to induction, followed by 50 mg of lidocaine to attenuate any burning on injection of etomidate and to blunt the response to tracheal intubation. The patient is induced with etomidate, paralyzed with vecuronium, and he is easily intubated. See Table 42–1.

Table 42–1 INTRAOPERATIVE MONITORING FOR RESECTION OF A PHEOCHROMOCYTOMA

Arterial line placed prior to induction Central venous catheter (possibly prior to induction) Standard ASA monitors Consider PA catheter for patients with LV dysfunction

APPROACH TO

Pheochromocytoma

Pheochromocytomas are tumors of the chromaffin cells occurring in the adrenal medulla. They are found in 0.1% of the population and typically present between the third and fifth decade of life. Pheochromocytomas arise from chromaffin cells typically in the adrenal medulla. However, these tumors may also originate anywhere chromaffin cells are located throughout the neural crest including areas along the sympathetic chains, the neural tissues at the bifurcation of the aorta (the organ of Zuckerkandl), the ureters, or the urinary bladder. When located outside of the adrenal medulla, these tumors are referred to as paraganglionomas.

The atypical cells of a pheochromocytoma may produce either epinephrine or norepinephrine, or a combination. It is not surprising that the patient’s symptomatology can vary with the type and amount of compound(s) produced. Symptoms can range from hypertension, tremulousness, occasional palpitations, and diaphoresis, although not all patients with pheochromocytoma are hypertensive. The most common symptoms include severe headaches, palpitations, and diaphoresis.

Biochemical markers are used when attempting to diagnose a pheochromocytoma. Plasma-free metanephrines, which are by-products of epinephrine metabolism, are considered the gold standard for biochemical testing, yielding 99% sensitivity and 89% specificity for pheochromocytoma.

A number of hereditary conditions are associated with familial pheochromocytomas and paraganglionomas. Multiple endocrine neoplasias (MEN) types II A and B are associated with pheochromocytomas, as are disorders of the neuroectoderm, such as von Hippel-Lindau syndrome, Sturge-Weber syndrome, and neurofibromatosis. MRIs are extremely sensitive for visualizing these masses, and exceed the retentivity of either CT scans, or ¹³¹I-MIBG scintigraphy in localizing extra-adrenal tumors.

Classic teaching dictates that 10% of pheochromocytomas are extra-adrenal, 10% are bilateral, and 10% are malignant. Also, 10% of pheochromocytomas present in children, 10% are familial, and 10% recur after surgery.

Preoperative Care of the Patient with Pheochromocytoma

In 1987, Roizen et al proposed criteria for the preoperative management of patients with pheochromocytoma. These criteria evaluate patients for their degree of preoperative adrenergic receptor blockade. Failure to meet the Roizen criteria prior to resection of the tumor is associated with a poor outcome. These criteria are:

• No BP measurement above 160/90 mm Hg should be observed for 24 hours preoperatively.

• Orthostatic hypotension with readings of 80/45 mm Hg should be present.

• The ECG should have no ST changes for at least 1 week prior to surgery.

• The patient should have no more than one PVC every 5 minutes.

Adrenergic receptor blockade is imperative prior to excision of a pheochromocytoma. The treatment initially targets the alpha receptors for blockade, followed by the beta receptors (if necessary). Alpha blockers commonly used for this purpose include phenoxybenzamine, doxazosin, prazosin, and terazosin. Phenoxybenzamine is a nonselective alpha blocker and has historically been considered the gold standard. It has the potential to induce reflex tachycardia, and a very long duration of action. Selective alpha-1 blockers, including doxazosin, prazosin, and terazosin, may be more efficacious due to their specificity for the alpha-1 receptor and shorter half-lives. Generally, beta receptors are only targeted after achieving adequate alpha blockade because of the risk of inducing iatrogenic congestive heart failure.

Intraoperative Considerations

Two considerations predominate when choosing anesthetic drugs for resection of a pheochromocytoma: avoid drugs which release catecholamines, and avoid drugs which release histamine. Drugs that cause histamine release include morphine, succinylcholine, pancuronium, and atracurium. Drugs which release or potentiate catecholamines include: ketamine (releases catecholamines), ephedrine (potentiates the release of catecholamines), meperidine (causes sympathetic stimulation), and succinylcholine (fasciculations may cause release of catecholamines). Halothane is relatively contraindicated in patients with pheochromocytomas secondary to its sensitization of the myocardium to catecholamines, potentially leading to fatal arrhythmias. It deserves mentioning, however, that halothane has been used successfully in hundreds of excisions in the past. Theoretically, desflurane should not be used in patients with pheochromocytomas due to increased sympathetic discharge at high concentrations, although it too has been used successfully in numerous excisions.

Both thiopental and propofol have been safely used for induction. If LV dysfunction is present, etomidate is the preferred choice. Vecuronium is probably the nondepolarizing neuromuscular blocker of choice, since it does not cause histamine release, and sevoflurane is an ideal inhalation anesthetic when excising pheochromocytomas although isoflurane is also acceptable.

Patients with undiagnosed pheochromocytomas can have severe hypertensive reactions to anesthetics, tracheal intubation, and the surgical stimulus. There are many potential agents which can be used to treat this hypertensive response (Table 42–2).

Table 42–2 AGENTS USED TO TREAT HYPERTENSION DURING RESECTION OF PHEOCHROMOCYTOMA
AGENT	MECHANISM OF ACTION
Sodium nitroprusside	Direct vasodilator
Nitroglycerin	Direct vasodilator
Phentolamine	Alpha-1, alpha-2 antagonist
Esmolol	Beta-1 antagonist
Nicardipine	Calcium channel blocker

Surgical Considerations

Effective communication between the anesthetic and surgical teams is of utmost importance during tumor resection. During surgical manipulation of the tumor, catecholamines can be released, thus precipitating a hypertensive crisis. By communicating, the teams can help predict these hemodynamic changes and intervene appropriately.

The resection of a pheochromocytoma can be undertaken either laparoscopically or via an open approach. Laparoscopic adrenalectomy is considered to be the procedure of choice, unless the patient has a demonstrated invasive tumor or a mass larger than 15 cm. Laparoscopic resection is seemingly associated with fewer incidences of hemodynamic instability when compared to a traditional laparotomy. Conversely, there is an increase in catecholamine release during insufflation of the abdomen, but the resultant hypertension is usually transient.

Comprehension Questions

42.1. A 52-year-old man presents to the preoperative anesthesia clinic prior to excision of his pheochromocytoma for evaluation and management of his hypertension. He has significant and worsening dyspnea on exertion. An echocardiogram demonstrates an LVEF of 38% with significant ventricular wall hypertrophy. A large-bore i.v. radial arterial line, and a central line are placed preoperatively and the patient is taken to the operating room. Which of the following agents are contraindicated for the induction of anesthesia?

A. Propofol

B. Etomidate

C. Ketamine

D. Thiopental

42.2. Just prior to exposure of the pheochromocytoma, during surgical dissection of Gerota fascia, the patient’s arterial pressure spikes to 220/120 mm Hg and continues to rise. Which of the following is contraindicated for the management of the hypertension in this setting?

A. Sodium nitroprusside drip

B. Esmolol drip

C. Nicardipine drip

D. Fenoldopam drip

ANSWERS

42.1. C. Ketamine is contraindicated in pheochromocytoma patients because ketamine indirectly releases catecholamines and can result in intractable systemic hypertension. Answers: A, B, and D, propofol, etomidate, and thiopental respectively are equally efficacious in the induction of general anesthesia with little risk of inducing a hypertensive state.

42.2. D. Fenoldopam is useful in inducing peripheral vasodilation via activation of the dopamine-1 receptor, but also induces diuresis. In the setting of pheochromocytomas, patients are usually hypovolemic at the time of tumor excision, and diuresis at this time is not warranted. Answers A, B, and C, sodium nitroprusside, esmolol, and nicardipine are useful to treat hypertensive crises in this setting.

Clinical Pearls

➤ Outcomes are improved if blood pressure is controlled, orthostatic hypotension is present, the CG has had no ST changes for the previous week, and if the patient has no more than one PVC every 5 minutes.

➤ Alpha blockade must be established prior to beta blockade.This should be followed by expansion of intravascular volume and normalization of myocardial performance.

➤ The increased blood pressure and hypermetabolism associated with pheochromocytomas may mimic other disorders including malignant hyperthermia and thyroid storm.

➤ Avoid drugs which stimulate or release catecholamines, and which release histamine.

➤ The principal postoperative complication is persistent hypotension refractory to volume replacement.

References

Kinney MA, Narr BJ, Warner MA. Perioperative management of pheochromocytoma. J Cardiothorac Vasc Anesth. 2002;16(3):359-369. 

Lenders J, Pacak K, Walther MM, et al. Biochemical diagnosis of pheochromocytomas. JAMA. 2002;287(11):1427-1434. 

Roizen MF, Fleisher LA. Anesthetic implications of concurrent diseases. In: Miller RD, ed. Miller’s Anesthesia. 6th ed. Philadelphia, PA: Elsevier Churchill Livingstone;2005: 1042-1044.

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