Am J Med. 2021 Apr 14:S0002-9343(21)00228-X. doi: 10.1016/j.amjmed.2021.03.015. Online ahead of print.
BACKGROUND: Pheochromocytoma is a rare cause of acute cardiovascular disease however, any severe illness may have high catecholamines, simulating pheochromocytoma. We determined the spectrum of urine metanephrines from inpatient and outpatient collections without pheochromocytoma compared to confirmed pheochromocytoma patients.
METHODS: Retrospective analysis using centralized laboratory data serving all outpatients and hospitals in southern Alberta. The analysis comprised 24 hour-urine normetanephrine and metanephrine(UNM-UMN) results collected from hospital inpatients, community outpatients and patients from a comprehensive provincial pheochromocytoma registry.
RESULTS: There were 974 unique inpatients including132 from intensive care, 6802 outpatients and 58 pheochromocytoma patients. Among outpatient, general ward and ICU patients, 18.7%, 34.4% and 67.4% of results were supranormal. Although pheochromocytoma patients had higher median UNM-UMN versus inpatients, there was substantial overlap. ROC analysis showed AUC between 0.64-0.91 to detect true pheochromocytoma(p<0.0001) with progressively poorer discrimination among hospitalized and ICU-dependent patients. A 24 hour-urine normetanephrine >6.95 nmol/d had 98% specificity for pheochromocytoma when inpatient general ward samples were included but only 46% sensitivity and 13% positive predictive value for pheochromocytoma. Considering ICU collections, 98% specificity required results more than 5-fold above the upper reference limit and still had poor positive predictive value. A model combining both UNM and UMN results as a cross-product marginally improved the ROC AUC but improved sensitivity in outpatients and ward patients but not ICU patients.
CONCLUSION: There is a high degree of overlap in UNM-UMN between hospitalized patients and pheochromocytoma; high test specificity is not achieved in this population unless >3-5 times the upper reference limit.