Pheochromocytomas are uncommon, catecholamine-releasing tumors, with about 85% to 90% of them located in the adrenal gland.1,2 The majority of pheochromocytomas (about 75%) are benign; however, hypersecretion of catecholamines can lead to hypertension, cardiovascular disease, and death. Proper diagnosis and treatment can reduce morbidity and mortality.3
The mean age at which sporadic pheochromocytoma is diagnosed is 47 years. A genetic susceptibility has been identified and occurs in up to 40% of patients; this genetic component occurs at a higher incidence than for any other solid tumor. The only cure for pheochromocytoma is surgery.3
Clinical manifestations and diagnostic considerations
Most of the signs and symptoms of pheochromocytomas are the result of epinephrine, norepinephrine, and dopamine release.1 There are differences in biochemical patterns, and only about half of pheochromocytomas secrete both epinephrine and norepinephrine.2
The most common signs and symptoms are: persistent or episodic hypertension, headache, sweating, palpitations, tachycardia, syncope, anxiety, tremor, hyperglycemia, and weight changes. Patients may also be asymptomatic.3
In the evaluation of pheochromocytoma, plasma or urine levels of normetanephrine and metanephrine indicative of catecholamine overproduction provide good diagnostic sensitivity.1
A treatable disorder
It is important to treat a pheochromocytoma due to the potential cardiovascular risks.4 The mainstay of treatment is the complete surgical removal of the lesion.2 Preoperative medical treatment is typically recommended in order to reduce symptoms of catecholamine excess and the risk of perioperative cardiovascular complications.4,5 Treatment generally starts with phenoxybenzamine to induce a long-lasting alpha-adrenergic blockage. Demser® (metyrosine) is a false catecholamine precursor that inhibits the enzyme tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. Demser® reduces catecholamine synthesis by up to 80%. The maximum biochemical effect usually occurs within two to three days, and the urinary concentration of catecholamines and their metabolites usually returns to pretreatment levels within three to four days after Demser® is discontinued. In some patients, the total excretion of catecholamines and catecholamine metabolites may be lowered to normal or near normal levels (less than 10 mg/24 hours).6
DEMSER® (metyrosine) is indicated in the treatment of patients with pheochromocytoma for:
preoperative preparation of patients for surgery, management of patients when surgery is
contraindicated, and chronic treatment of patients with malignant pheochromocytoma. Demser is not
recommended for the control of essential hypertension.
IMPORTANT SAFETY INFORMATION
- Demser is contraindicated in persons known to be hypersensitive to this compound.
- Maintain adequate intravascular volume intraoperatively (especially after tumor removal) and postoperatively to avoid hypotension and decreased perfusion of vital organs resulting from vasodilatation and expanded volume capacity.
- Life-threatening arrhythmias may occur during anesthesia and surgery. Monitor blood pressure and electrocardiogram continuously during surgery.
- DEMSER does not eliminate the danger of hypertensive crises or arrhythmias during manipulation of the tumor, and the alpha-adrenergic blocking drug, phentolamine, may be needed.
- DEMSER may add to the sedative effects of alcohol and other CNS depressants, e.g., hypnotics, sedatives, and tranquilizers.
- To minimize the risk of crystalluria, patients should be urged to maintain water intake sufficient to achieve a daily urine volume of 2000 mL or more, particularly when doses greater than 2 g per day are given. Routine examination of the urine should be carried out. If metyrosine crystalluria occurs, fluid intake should be increased further. If crystalluria persists, the dosage should be reduced or the drug discontinued.
- Observe caution in patients with impaired hepatic or renal function.
- Warn patients about engaging in activities requiring mental alertness and motor coordination, such as driving a motor vehicle or operating machinery.
- Advise patients to maintain liberal fluid intake.
- Use caution in administering DEMSER to patients receiving phenothiazines or haloperidol because the extrapyramidal effects of these drugs can be expected to be potentiated by inhibition of catecholamine synthesis.
- The most common adverse reaction to DEMSER is moderate to severe sedation. Other commonly reported adverse reactions are extrapyramidal signs such as drooling, speech difficulty and tremor in approximately 10 percent of patients, occasionally accompanied by trismus and frank Parkinsonism. Anxiety and psychic disturbances such as depression, hallucinations, disorientation, and confusion may occur. Diarrhea occurs in about 10 percent of patients and may be severe.
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References: 1. Pappachan JM, Raskauskiene D, Sriraman R, Edavalath M, Hanna FW. Diagnosis and management of pheochromocytoma: A practical guide to clinicians. Curr Hypertens Rep. 2014;16(7):442.
2. Tsirlin A, Oo Y, Sharma R, Kansara A, Gliwa A, Banerji MA. Pheochromocytoma: A review. Maturitas. 2014;77(3):229-238.
3. Fishbein L. Pheochromocytoma and paraganglioma: Genetics, diagnosis, and treatment. Hematol Oncol Clin North Am. 2016;30(1):135-150.
4. Mannelli M, Dralle H, Lenders JWM. Perioperative management of pheochromocytoma/paraganglioma: Is there a state of the art? Horm Metab Res. 2012;44(5):373-378.
5. Wachtel H, Kennedy EH, Zaheer S, et al. Preoperative metyrosine improves cardiovascular outcomes for patients undergoing surgery for pheochromocytoma and paraganglioma. Ann Surg Oncol. 2015; 22(suppl 3):S646-S654.
6. Demser [package insert]. Bridgewater, NJ: Aton Pharma Inc; 2015.