eMedicine Specialties > Endocrinology > Adrenal Gland
Pheochromocytoma: Treatment & Medication
Updated: Jul 31, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
Surgical resection of the tumor is the treatment of choice and usually results in cure of the hypertension. Careful treatment with alpha and beta blockers is required preoperatively to control blood pressure and prevent intraoperative hypertensive crises.12
- Start alpha blockade with phenoxybenzamine 7-10 days preoperatively to allow for expansion of blood volume.
- The patient should undergo volume expansion with isotonic sodium chloride solution. Encourage liberal salt intake.
- Initiate a beta blocker only after adequate alpha blockade. If beta blockade is started prematurely, unopposed alpha stimulation could precipitate a hypertensive crisis.
- Administer the last doses of oral alpha and beta blockers on the morning of surgery.
Surgical Care
An experienced anesthesiologist and an experienced surgeon are crucial to the success of the operation. Surgical mortality rates are less than 2-3% with an experienced anesthesiologist and surgeon.
- Use an arterial line, cardiac monitor, and Swan-Ganz catheter. Administer stress-dose steroids if bilateral resection is planned.
- An anterior midline abdominal approach was used in the past; however, in current practice, laparoscopic adrenalectomy is the preferred procedure for lesions smaller than 8 cm. If the pheochromocytoma is intra-adrenal, remove the entire adrenal gland. In the case of a malignant pheochromocytoma, resect as much of the tumor as possible.
Medication
Medical therapy is used for preoperative preparation prior to surgical resection, acute hypertensive crises, and primary therapy for patients with metastatic pheochromocytomas. Preoperative preparation requires combined alpha and beta blockade to control blood pressure and to prevent an intraoperative hypertensive crisis. Alpha-adrenergic blockade, in particular, is required to control blood pressure and prevent a hypertensive crisis. High circulating catecholamine levels stimulate alpha receptors on blood vessels and cause vasoconstriction.
Phenoxybenzamine (Dibenzyline) is the preferred alpha blocker in preparation for surgery. After effective alpha blockade, administer a beta blocker. Beta blockers are needed to control the tachycardia associated with high circulating catecholamine levels and alpha blockade. Beta-adrenergic blockers are used if significant tachycardia occurs after alpha blockade. Only administer beta-adrenergic blockers after adequate alpha blockade because unopposed alpha-adrenergic receptor stimulation can precipitate a hypertensive crisis. Noncardioselective beta blockers, such as propranolol (Inderal) or nadolol (Corgard), are often used; however, cardioselective agents, such as atenolol (Tenormin) and metoprolol (Lopressor), also may be used.
Labetalol (Trandate, Normodyne) is a noncardioselective beta-adrenergic blocker and selective alpha-adrenergic blocker that has been shown to be effective in controlling hypertension associated with pheochromocytoma. It has also been associated with paradoxic episodes of hypertension thought to be secondary to incomplete alpha blockade. Thus, its use in the preoperative treatment of patients with pheochromocytoma is controversial.
During surgery, intravenous phentolamine, a rapid-acting alpha-adrenergic antagonist, is used to control blood pressure. Rapid-acting intravenous beta blockers, such as esmolol, are also used to normalize blood pressure. Selective alpha1 blocking agents, such as prazosin (Minipress), terazosin (Hytrin), and doxazosin (Cardura), have more favorable adverse effect profiles and are used when long-term therapy is required (metastatic pheochromocytoma). These medications are not used to prepare patients for surgery because of their incomplete alpha blockade.
Alpha-adrenergic receptor blockers
At low doses, alpha-adrenergic receptor blockers may be used as monotherapy in the treatment of hypertension. At higher doses, they may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of alpha-receptor blockers.
Phenoxybenzamine hydrochloride (Dibenzyline)
Long-acting adrenergic alpha-receptor blocker that can produce and maintain a chemical sympathectomy. Lowers supine and upright BPs. Does not affect parasympathetic nervous system.
Adult
10 mg PO bid, increase by 10 mg qod until optimum dose achieved
Dose range: 20-40 mg PO bid/tid
Pediatric
Not established
When used concurrently, alpha-adrenergic agonists decrease effects of medication; beta blockers increase toxicity
Documented hypersensitivity; patients in whom a fall in BP is undesirable
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in cerebral or coronary arteriosclerosis and renal impairment; can worsen symptoms of respiratory tract infections
Doxazosin mesylate (Cardura)
Quinazoline compound that is a selective alpha1-adrenergic antagonist. Inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of veins and arterioles and decrease in total peripheral resistance and BP.
Adult
1 mg PO qd; may increase to 2 mg qd thereafter and titrate to higher doses; not to exceed 8 mg qd
Pediatric
Not established
Effects decrease with coadministration of NSAIDs; effects increase with coadministration of diuretics and antihypertensive medications
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal impairment; may cause marked hypotension following first dose; rarely (<1 in 1000 patients), priapism may occur
Phentolamine mesylate (Regitine)
Nonselective alpha-adrenergic blocking agent. Drug action is transient and alpha-adrenergic blockade incomplete. Often used immediately prior to or during adrenalectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor. Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on alpha receptors.
Adult
5-15 mg IV; used to control intraoperative hypertensive crises
Pediatric
0.05-1 mg/kg per dose IV/IM, repeat q2-4h prn until hypertension is controlled; used prior to surgical removal of a tumor or to treat acute paroxysmal hypertensive crisis
Concurrent administration of epinephrine or ephedrine may decrease phentolamine effects; ethanol increases phentolamine toxicity
Documented hypersensitivity; coronary or cerebral arteriosclerosis; renal impairment; myocardial infarction or a history of a myocardial infarction
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in tachycardia, peptic ulcer, and gastritis; cerebrovascular occlusions and myocardial infarctions can occur following administration
Vasodilators
Reduce systemic vascular resistance, allowing more forward flow and improving cardiac output.
Nitroprusside (Nipride)
Direct vasodilator that relaxes arterial vessels and venous smooth muscle. Has short half-life and effect disappears within 5 min of stopping infusion. May use to control paroxysmal hypertension intraoperatively. Produces vasodilation and increases inotropic activity of heart. At higher dosages may exacerbate myocardial ischemia by increasing heart rate.
Adult
Begin infusion: 0.3-0.5 mcg/kg/min IV; use increments of 0.5 mcg/kg/min, titrate to desired effect
Average dose: 1-6 mcg/kg/min IV; infusion rates >10 mcg/kg/min may lead to cyanide toxicity
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis; atrial fibrillation or flutter
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; in renal or hepatic insufficiency, levels may increase and can cause cyanide toxicity; sodium nitroprusside can lower BP (only use in patients with mean arterial pressures >70 mm Hg)
Beta-adrenergic receptor blocking agents
These agents compete with beta-adrenergic agonists for available beta-receptor sites.
Propranolol hydrochloride (Inderal)
Nonselective beta-adrenergic receptor blocker. After primary treatment with an alpha-receptor blocker, may be used as adjunctive therapy if control of tachycardia becomes necessary before or during surgery. May be used to treat excessive beta-receptor stimulation in patients with inoperable metastatic pheochromocytoma. Has membrane-stabilizing activity and decreases automaticity of contractions.
Not suitable for emergency treatment of hypertension. Do not administer IV in hypertensive emergencies.
Adult
Preoperative preparation: 10 mg PO tid/qid, titrate up prn; 60 mg/d in divided doses is usual dose required
During surgery: 1-3 mg IV to control tachycardia (careful monitoring)
Metastatic pheochromocytoma: 30 mg PO in divided doses
Pediatric
1 mg/kg PO qd, titrate prn; IV not recommended
Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines may increase
Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, inducing thyroid storm; withdraw drug slowly and monitor closely
Atenolol (Tenormin)
Selectively blocks beta1 receptors with little or no affect on beta2 types.
Adult
50 mg PO qd; increase to 100 mg/d if necessary
Pediatric
1-2 mg/kg PO qd
Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity
Documented hypersensitivity; congestive heart failure; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without a pacemaker)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during an IV, carefully monitor BP, heart rate, and ECG
Tyrosine kinase inhibitors
Used to inhibit catecholamine synthesis in pheochromocytoma.
Metyrosine (Demser)
Inhibits tyrosine hydroxylase, the rate-limiting step in catecholamine synthesis. In patients with pheochromocytoma, administration of metyrosine reduces catecholamine biosynthesis by 35-80% as measured by urinary catecholamine levels. Indicated in malignant pheochromocytoma or pheochromocytoma when surgery is contraindicated. Inhibits catecholamine synthesis in pheochromocytoma. Can be useful in patients who are refractory to phenoxybenzamine therapy, or can be administered as adjunct to phenoxybenzamine therapy.
Adult
250 mg PO qid initially, titrated up by 250-500 qd prn; not to exceed 4 g qd in divided doses; monitor clinical symptoms and catecholamine excretion
Optimal benefits: 2-3 g PO divided qid (typically)
Preoperatively: Administer for at least 5-7 d
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Ethanol, TCAs, opiate agonists, barbiturates, benzodiazepines, H1 blockers, or other CNS agents can result in additive sedative effects; extrapyramidal effects of haloperidol, metoclopramide, molindone, or phenothiazines can be increased
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Instruct patients to maintain adequate fluid balance (daily urinary volume of >2 L) to minimize risk of metyrosine-induced crystalluria; increase fluid intake if crystalluria occurs; if crystalluria persists, dosage reduction or discontinuation may be necessary; precipitates extrapyramidal symptoms, including increased salivation, tremor, and speech difficulty; other more infrequent effects include trismus and pseudoparkinsonism; can precipitate or worsen mental depression, resulting in effects such as anxiety, tremulousness, confusion, and psychic disturbances; other adverse effects may include dry mouth, impotence or ejaculation dysfunction (failure to ejaculate), hematologic toxicity, galactorrhea, swelling of the breasts, peripheral edema, and urticaria
More on Pheochromocytoma |
| Overview: Pheochromocytoma |
| Differential Diagnoses & Workup: Pheochromocytoma |
 Treatment & Medication: Pheochromocytoma |
| Follow-up: Pheochromocytoma |
| Multimedia: Pheochromocytoma |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Further Reading
Clinical guidelines:
ACR Appropriateness Criteria® incidentally discovered adrenal mass. American College of Radiology - Medical Specialty Society. 2000 (revised 2007). 8 pages. NGC:005995
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of hypertension. American Association of Clinical Endocrinologists - Medical Specialty Society. 2006 Mar-Apr. 30 pages. NGC:005007
VHA/DoD clinical practice guideline for the diagnosis and management of hypertension in the primary care setting. Department of Defense - Federal Government Agency [U.S.]
Department of Veterans Affairs - Federal Government Agency [U.S.]
Veterans Health Administration - Federal Government Agency [U.S.]. 1999 May (revised 2004). 99 pages. NGC:004198
Clinical trials:
A Broad Multi-Histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) In Advanced Colorectal, Non-Small Cell Lung, Head and Neck, Hepatocelluar and Renal Cell Carcinomas and Pheochromocytoma and Thyroid Tumors
A Study Evaluating Ultratrace Iobenguane I 131(MIBG)in Patients With Malignant Pheochromocytoma/Paraganglioma
Content Validation of Quality of Life and Symptom Questionnaires for Pheochromocytoma and Paraganglioma
Diagnosis of Pheochromocytoma
Study Of Sunitinib In Patients With Recurrent Paraganglioma/Pheochromocytoma (SNIPP)
Keywords
pheochromocytoma, adrenal gland, adrenal glands, catecholamine, catecholamines, paraganglioma, multiple endocrine neoplasia, catecholamine-secreting tumor, extra-adrenal pheochromocytomas, familial pheochromocytoma, sporadic pheochromocytoma, multiple endocrine neoplasia 2A, multiple endocrine neoplasia 2B, MEN 2A, MEN 2B, neurofibromatosis, von Hippel-Lindau disease, VHL disease, pheochromocytoma-induced hypertensive crises, hypertensive encephalopathy, Von Recklinghausen disease, Sipple syndrome, tuberous sclerosis, Bourneville disease, Epiloia, Sturge-Weber syndrome, Cushing syndrome, postural hypotension, hypertensive retinopathy, cafe au lait spots
