Measurement of biogenic amines

There are a variety of biochemical tests for the detection of phaeochromocytoma and functional (secretory) paraganglioma including catecholamines and their methylated metabolites (“metanephrines”; metanephrine and normetanephrine) and 3-methoxytyramine. Plasma, serum, or urine can be used.

We recommend following the Endocrine Society Clinical Practice Guidelines for biochemical screening for paraganglioma/phaeochromocytoma:

• Measure plasma free or urinary fractionated metanephrines
• If appropriate also measure 3-methoxytyramine
• Collect plasma samples after the patient has rested in the seated position for 10 minutes 
• In certain circumstances repeat sampling may be recommended by the referring clinician; if this occurs collection after 30 minutes of rest in the supine position may be appropriate
• If measuring plasma 3-methoxytyramine, sampling should be done after an overnight fast.

Link to advice for patients having tests to measure biogenic amines.

Test choice

• Measurement of plasma or urine metanephrines has higher diagnostic accuracy than measurement of the parent catecholamines (adrenaline and noradrenaline).
• Practical issues including better chemical stability and less need to adjust diet and medication favour metanephrines over catecholamines.
• Ease of sample collection favours plasma samples over 24-hour urine collections.
• Measurement of plasma 3-methoxytyramine may improve diagnostic sensitivity in some settings (e.g. detection of head and neck paraganglioma).

Interpretation of results

• Positive results need to be interpreted taking the pre-test probability and the use of potentially interfering medications into account.
• Metanephrine and/or catecholamine levels may be abnormal when a person does not have a tumour (false positive).
• Metanephrine and/or catecholamine levels may be normal when a tumour is present (false negative), although a false negative is less common than a false positive.
• A number of medications have been reported to cause false positive results, including paracetamol, mesalazine, sulfasalazine (interfere with some measurement methods) and tricyclic antidepressants (interfere with disposition of catecholamines).
• Medications have not been reported to cause false negative results.
• For plasma free metanephrines, dietary considerations are only relevant when measurements include the dopamine metabolite 3-methoxytyramine.

Patients at increased risk of phaeochromocytoma and/or functional paraganglioma should be made aware of important symptoms and asked to report them to their doctor should they occur. Concerning symptoms include changes in vision (especially if sudden), episodes of palpitations with sweating (may be associated with feelings of panic), constant pain, and tingling or abnormal sensation in limbs, dizzy turns, alteration in ability to perform a fine movement (e.g. doing up a button).

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Bibliography

Lenders, J. W., Q. Y. Duh, G. Eisenhofer, et al. 2014. "Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline." J Clin Endocrinol Metab 99(6):1915-1942.

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OBJECTIVE: The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). PARTICIPANTS: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. CONCLUSIONS: The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines. Consideration should be given to preanalytical factors leading to false-positive or false-negative results. All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications. Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas. Partial adrenalectomy is an option for selected patients. Lifelong follow-up is suggested to detect recurrent or metastatic disease. We suggest personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes.