UBP 2.4 (Short Form): Endocrine - Pheochromocytoma

Question 1

Are the signs and symptoms of this patient consistent with pheochromocytoma?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 1

His hypertension (continuous or paroxysmal), headaches, palpitations, and sweating are all consistent with pheochromocytoma.

These symptoms, along with pallor, flushing, tremor, nausea, vomiting, and orthostatic hypotension (secondary to hypovolemia), are manifestations of excessive secretion of catecholamines (norepinephrine and epinephrine) from the tumor.

While this patient’s decreased energy could be caused by a number of things, it could reflect – a catecholamine-induced cardiomyopathy or congestive heart failure secondary to sustained hypertension.

Additionally, pheochromocytoma is associated with –

stroke, myocardial ischemia, sugar intolerance, and acute renal failure.

Question 2

How is the diagnosis of pheochromocytoma confirmed?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 2

There are a number of tests available for the diagnosis of pheochromocytoma based on the presence and/or metabolites of excessive catecholamines.

The measurement of free metanephrines in the plasma may be the most reliable test for confirming the diagnosis.

Other tests include measuring –

• plasma catecholamines,
• plasma chromagranin A,
• total urinary catecholamines,
• urinary metanephrines, and
• urinary vanillylmandelic acid.

When preliminary test results are equivocal, the clonidine suppression test may prove helpful (clonidine lowers plasma catecholamines levels in patients with essential hypertension, but does not lower the levels in patients with pheochromocytoma).

Localization of the tumor may be achieved with magnetic resonance imaging (most appropriate in pregnant women), computed tomography, and scintigraphy with metaiodobenzyl guanidine (MIBG).

Question 3

What evaluation would you require prior to surgery?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 3

In preparing this patient with pheochromocytoma and decreased energy for surgery, I would require –

• an ECG to look for signs of left ventricular hypertrophy and identify any nonspecific T-wave changes;
• a chest x-ray to identify any cardiomegaly or signs of COPD;
• an echocardiogram to evaluate cardiac function (due to the decreased energy level); and
• a CBC to identify an elevated hematocrit (which is suggestive of hypovolemia).

Concurrently, I would ensure –

• adequate alpha-adrenergic blockade (phenoxybenzamine);
• ß-blockade, if needed to treat tachycardia (heart rate > 120 bpm) and/or arrhythmias (in either case, alpha-blockade should proceed B-blockade); and,
• if appropriate, cautious volume replacement, keeping in mind the potential for congestive heart failure with overaggressive fluid administration.

I would also perform a careful history to determine the severity of the patient’s –

• acid reflux and,
• if I suspected COPD, consider ordering pulmonary function studies to obtain a diagnosis, determine the severity of the disease, and identify a reversible component.

Depending on my findings, I would then attempt to optimize the patient’s condition with bronchodilators, glucocorticoids, chest physiotherapy, and a proton pump inhibitor.

Question 4

What is the optimal duration of alpha-blockade prior to surgery?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 4

While the optimal duration of alpha-blockade is unknown,

most experts recommend initiating blockade at least 10-14 days prior to surgery.

This allows time to stabilize the blood pressure and normalize intravascular volume {“to establish euvolemic status”}, since prior to treatment, these patients tend to have a reduced intravascular volume secondary to catecholamine-induced increases in SVR.

Some clinicians recommend discontinuing alpha-blockade 24-48 hours prior to surgery or administering a half dose on the morning of surgery to reduce the risk of significant hypotension following vascular isolation of the tumor (abruptly stopping secretion of catecholamines).

Others recommend continuing full alpha-blockade through surgery to minimize catecholamine-related complications, believing that the benefits of continued blockade outweigh the risk of intraoperative hypotension.

Question 5

How does alpha-Methylparatyrosine work?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 5

(This question was thrown in to see how you’d handle a question you do not know.)

alpha-Methylparatyrosine (alpha-Methyl tyrosine or metyrosine) inhibits the rate-limiting enzyme, tyrosine hydrolase, of the catecholamine synthetic pathway, which results in a 40-80% reduction in catecholamine synthesis.

Although this drug is very effective, it is currently limited to patients with metastatic disease or those requiring long term medical therapy (i.e. surgery is contraindicated) due to significant side effects, including diarrhea, sedation, anxiety, depression, extrapyramidal reactions, and crystalluria.

Question 6

The surgeon asks the patient to discontinue phenoxybenzamine 24 hours prior to surgery. Is this ok?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 6

This is reasonable because,

as I mentioned before, discontinuing alpha-blockade 24-48 hours prior to surgery may reduce the risk of significant hypotension following tumor removal.

Interruption of the vascular supply to the tumor results in an abrupt cessation of catecholamine secretion from the tumor into the blood stream.

This reduction in circulating catecholamines combined with – hypovolemia, vasodilation from residual alpha-blockade, and cardiovascular depression from anesthesia, can lead to significant hypotension.

If hypotension did occur following tumor resection, my initial treatment would be to ensure adequate volume replacement with crystalloid or blood.

If the hypotension were severe or persistent, I would consider vasopressor therapy;

if I suspected hypoadrenalism (i.e. bilateral adrenalectomies), I would consider steroid supplementation.

Question 7

Is it important to establish alpha-blockade prior to starting a ß-blocker?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 7

It is important to establish alpha-blockade prior to administering a nonselective B-blocker.

This is because –

blockade of vasodilatory B2-receptors could result in unopposed vasoconstriction, hypertensive crisis, and congestive heart failure due to the effects of excessive circulating catecholamines on alpha-receptors.

Question 8

What do you think about his decreased energy level?

Would you require an echocardiogram?

(A 56-year-old male presents for resection of an abdominal pheochromocytoma. He has a history of poorly controlled hypertension, recurrent headaches, palpitations, and sweating. He complains of decreased energy for the past 6 months, and daily acid reflux that he treats with Tums. He also admits to a 30-year history of smoking. VS: P = 76; BP = 116/72 mmHg; R = 10; T = 37ºC)

Answer 8

The patient’s reported decrease in energy is concerning to me because it could be secondary to catecholamine-induced cardiomyopathy and congestive heart failure.

EIther one of these conditions may result in inadequate cardiac output and a decreased energy level.

Given this symptomatology and the potential for significant cardiovascular instability during this case (changes in catecholamine levels and pneumoperitoneum formation), I feel that a more accurate measure of preoperative cardiac function would be beneficial.

Therefore, I would require an echocardiogram prior to starting the procedure.