A 61-year-old man with fluctuating hypertension
PHEOCHROMOCYTOMA: A CATECHOLAMINE-SECRETING TUMOR
The pathophysiology of pheochromocytoma is complex. It is characterized by accelerated growth of cells producing catecholamines, which may produce symptoms when secreted into the bloodstream. The classic triad of symptoms is headache, hypertension, and hyperglycemia, although our patient had very low blood sugar levels. Other common symptoms are nausea, orthostasis, and tremor, although not all symptoms are invariably seen.
Genetic testing recommended
Genetic associations have been described and are thought to be responsible for 20% to 30% of cases of pheochromocytoma. All associated germline mutations are autosomal dominant, some with variable penetrance. These include:
- Succinate dehydrogenase subunit B, C, and D mutations
- von Hippel-Lindau syndrome
- Multiple endocrine neoplasia type 1 and type 2 syndromes
- Neurofibromatosis type 1.13,14
The succinate dehydrogenase subunit mutations have been associated with, but not limited to, extra-adrenal adenomas (paragangliomas) and carry a worse prognosis.
Some experts recommend genetic testing in all cases of pheochromocytoma, sporadic or familial, and this testing should be followed by counseling if a mutation is found.15 Others recommend genetic testing based on the patient’s age (under age 50), history, imaging, and biochemical features of the tumor (metanephrines predominate in multiple endocrine neoplasia syndromes, and normetanephrines in von Hippel-Lindau syndrome).13
Serious consequences
A thorough evaluation is recommended, since pheochromocytoma has been associated with increased cardiovascular morbidity. In a retrospective series, Stolk et al10 reported that patients with pheochromocytoma had a higher incidence of myocardial infarction, angina, and stroke in the years preceding the diagnosis than did patients with essential hypertension (13.8% vs 1.1%, P < .001).10
Catecholamine cardiomyopathy has been described and shares clinical features with Takotsubo or stress cardiomyopathy, with global left ventricular systolic and diastolic dysfunction that improve or resolve after the adrenergic insult is removed.16
Conditions that warrant further evaluation or that may suggest pheochromocytoma are malignant hypertension, hypertensive encephalopathy, ischemic stroke, subarachnoid hemorrhage, acute pulmonary edema, angina pectoris, myocardial infarction, aortic dissection, and kidney injury.
When to suspect pheochromocytoma
Pheochromocytoma should be suspected in a patient with resistant hypertension, family history, or imaging findings that suggest an adrenal mass with a heterogeneous appearance. The diagnostic algorithm follows the same pathway as for the evaluation of an incidentally found adrenal mass, with determination of its dimension and characteristics by CT or MRI, and with biochemical testing of urine catecholamines, plasma free metanephrines, renin, aldosterone, and cortisol.
The diagnosis of pheochromocytoma is established by obtaining fractionated metanephrines and catecholamines in a 24-hour urine collection (sensitivity 90%, specificity 98%). Analysis of plasma metanephrines has a higher sensitivity (97%) but lower specificity (85%).17 The combination of typical signs, symptoms, and laboratory findings makes the diagnosis likely, especially in combination with a unilateral adrenal mass.
Laparoscopic surgery after medical preparation for active tumors
If the mass appears benign and not biochemically hyperactive, then follow-up at 1 year is recommended, with repeat testing. Surgical evaluation and intervention is recommended for lesions that appear malignant or that are biochemically active and clinically symptomatic.9
Preoperative hemodynamic control is essential in the management of pheochromocytoma to prevent or minimize hemodynamic changes that can be driven by increased catecholamines. Control is typically achieved with initial alpha-blockade and then beta-blockade to avoid worsening hypertension and to prevent an acute hypertensive crisis during surgical intervention. Phenoxybenzamine, the mainstay of therapy, is a nonselective alpha-blocker with a long duration of action that requires titration over several days up to 3 weeks.
A selective alpha-1-blocker such as doxazosin can be used to control postoperative hypotension, as it has a shorter half-life than phenoxybenzamine. Alternative strategies include calcium channel blockers, centrally acting sympathetic blockers, and magnesium.18
Laparoscopic adrenalectomy by an experienced surgeon after excellent medical preparation is often considered the treatment of choice, but for larger or malignant masses, an open procedure is recommended. The risk of perioperative morbidity and death can be reduced by adequate medical management. With successful surgical resection, the long-term prognosis is favorable.
