Can a pheochromocytoma (pheo) be ruled out in a young patient with anxiety who has elevated total metanephrines and dopamine levels in a 24-hour urine test?

From the Guidelines

Pheochromocytoma can be ruled out in this young patient with anxiety who has elevated total metanephrines and dopamine levels in a 24-hour urine test, as the elevations are likely due to other factors such as anxiety itself or other non-pheochromocytoma related conditions, and not indicative of a pheochromocytoma. According to the American Heart Association scientific statement 1, the screening test of choice for pheochromocytoma/paraganglioma is measurement of circulating catecholamine metabolites, and the levels are usually <4 times the upper limit of normal in hypertensive patients with false positives. The patient's symptoms such as palpitations, sweating, and hypertension can be mimicked by anxiety, and it is essential to consider other diagnoses before pursuing further testing for pheochromocytoma. Some key points to consider in this patient's evaluation include:

• The prevalence of pheochromocytoma is estimated at 0.01% to 0.2% in the general population, and the patient's symptoms and laboratory results do not strongly suggest this diagnosis 1.
• Anxiety can cause symptoms that mimic pheochromocytoma, such as palpitations, sweating, and hypertension, and it is essential to address the underlying anxiety through cognitive behavioral therapy, mindfulness techniques, or possibly medication such as SSRIs if symptoms are severe.
• The patient's laboratory results, although elevated, do not meet the criteria for further evaluation for pheochromocytoma, and clonidine-suppression testing can be used to further evaluate false positives with 100% specificity and 96% sensitivity of failure to reduce plasma metanephrines by 40% 1. It is crucial to consider the patient's overall clinical presentation and not rely solely on laboratory results to make a diagnosis, and to prioritize the patient's quality of life and minimize unnecessary testing and anxiety.

From the Research

Ruling Out Pheochromocytoma in Young Patients

• A pheochromocytoma (pheo) cannot be ruled out solely based on elevated total metanephrines and dopamine levels in a 24-hour urine test, as these results can be influenced by various factors, including anxiety 2.
• The diagnosis of pheochromocytoma should be established biochemically by measuring plasma free metanephrines and urinary fractionated metanephrines 3.
• In cases where the results are equivocal, additional tests such as the clonidine test may be performed to confirm the diagnosis 4.
• Imaging tests, including computed tomography (CT) or magnetic resonance imaging (MRI), are used to localize the tumor once the biochemical diagnosis is made 3, 2.

Clinical Considerations

• Pheochromocytomas can present with non-specific symptoms, including anxiety, and may be asymptomatic in 10-17% of cases 5.
• The majority of pheochromocytomas are endocrine-active tumors that secrete excess catecholamines, leading to clinical symptoms such as hypertension, headaches, and palpitations 2.
• Approximately 20% of pheochromocytomas are diagnosed in childhood, and the male/female ratio is 2/1 2.

Diagnostic Approach

• Measurements of plasma free metanephrines can provide useful information about the likely presence or absence of a pheochromocytoma, as well as predict tumor size and location 6.
• Elevated metanephrines are a key factor in establishing the diagnosis of pheochromocytoma, and genetic testing should be considered in cases where there is a risk of hereditary mutation 4.