A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma

Anna M Sawka¹^,2^,3 , Ally PH Prebtani²^,4 , Lehana Thabane⁵^,6 , Amiram Gafni⁶ , Mitchell Levine¹^,5^,6 and William F Young Jr⁷

¹Department of Internal Medicine, St. Joseph's Healthcare, Hamilton, Ontario, L8N 4A6, Canada

²Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada

³Hoffmann-La Roche Research Fellow in Health Economics, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada

⁴Department of Internal Medicine, Hamilton General Hospital, Hamilton, Ontario, L8L 2X2, Canada

⁵Centre for Evaluation of Medicines, St. Joseph's Healthcare, Hamilton, Ontario, L8N 1G6, Canada

⁶Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada

⁷Division of Endocrinology, Metabolism, Nutrition, and Internal Medicine, Mayo Clinic, Rochester, MN, 55905, USA

author email corresponding author email

BMC Endocrine Disorders 2004, 4:2doi:10.1186/1472-6823-4-2


Published:	29 June 2004

Abstract

Background

Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma.

Methods

We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted.

Results

Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%–100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%–100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07).

Conclusion

Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.