From the Guidelines
A slight elevation in serum metanephrines is not necessarily indicative of pheochromocytoma/paraganglioma, but rather may be a false positive result due to various factors such as obesity, OSA, or certain medications like tricyclic antidepressants 1.
Key Points to Consider
- The sensitivity and specificity of plasma free metanephrines are 96%−100% and 89%−98%, respectively, making it a reliable screening test for pheochromocytoma/paraganglioma 1.
- A slight elevation in serum metanephrines, typically less than 4 times the upper limit of normal, may require repeat testing to confirm the results 1.
- Clonidine-suppression testing can be used to further evaluate false positive results, with a 100% specificity and 96% sensitivity of failure to reduce plasma metanephrines by 40% 1.
- Imaging studies should only be pursued after biochemical evidence for a pheochromocytoma has been obtained 1.
Clinical Implications
- In patients with a strong clinical suspicion of pheochromocytoma, despite modestly elevated plasma or urine metanephrines, stimulation or suppression tests can be carried out to confirm the diagnosis 1.
- Twenty-four-hour urine fractionated metanephrines are an acceptable alternative to plasma metanephrines, especially in patients who are continent of urine 1.
From the Research
Significance of Slight Elevation in Serum Metanephrines
- A slight elevation in serum metanephrines may not be highly suggestive of pheochromocytoma or paraganglioma (PPGL), as marked elevations (> 3 times the upper limit of normal) are more indicative of these conditions 2.
- Serum metanephrines determination can be used for the diagnosis of pheochromocytoma, with a sensitivity of 100% and a specificity of 94% above a threshold value of 50 nmol/l in patients with normal renal function 3.
- However, renal insufficiency can affect serum metanephrine levels, with patients on hemodialysis having higher plasma concentrations of catecholamines and free metanephrines, and even higher plasma concentrations of deconjugated metanephrines 4.
- It is essential to consider the clinical context and potential interfering factors, such as renal insufficiency or incorrect urinary volume collection, when interpreting metanephrine test results 4, 5.
- The measurement of urinary metanephrines using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a recommended approach due to its high sensitivity, specificity, and throughput 6.
Potential Causes of Elevation
- Renal insufficiency can lead to elevated serum metanephrine levels, making it essential to consider renal function when interpreting test results 4, 3.
- Incorrect urinary volume collection can result in false elevations of urinary metanephrines, highlighting the need for accurate collection and measurement procedures 5.
- Other factors, such as comorbidities or interfering medications, may also affect metanephrine levels, although the relationship between these factors and metanephrine elevations is not always clear 2.