OR29-4 Biochemical diagnosis of pheochromocytoma using plasma free normetanephrine, metanephrine and methoxytyramine: Importance of supine sampling under fasting conditions

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR29-Adrenal Tumors & Pheochromocytoma
Translational
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:00 PM
Room 134 (Moscone Center)
Roland Därr*1, Mirko Peitzsch1, Christina Pamporaki1, Konstanze Miehle2, Aleksander Prejbisz3, Martin Fassnacht4, Felix Beuschlein5, Anthony Stell6, Stefan Richard Bornstein1, Hartmut P Neumann7, Andrzej Januszewicz3, Jacques W.M. Lenders8 and Graeme Eisenhofer1
1University Hospital Carl Gustav Carus, Dresden, Germany, 2University Hospital Leipzig, Leipzig, Germany, 3Institute of Cardiology, Warsaw, Poland, 4Univ of Wuerzburg, Wuerzburg, Germany, 5University of Munich, Munich, Germany, 6University of Melbourne, Melbourne, Australia, 7Medizinische Univ Klinik, Freiburg Im Breisgau, Germany, 8Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
Objective: To document influences of blood sampling under supine fasting versus seated non-fasting conditions on diagnosis of pheochromocytoma using plasma concentrations of normetanephrine, metanephrine and methoxytyramine (P-NMN/MN/MTY).

Design and Methods: P-NMN/MN/MTY were measured by liquid chromatography with tandem mass spectrometry in 765 patients at six centers, two of which complied with requirements for supine sampling after an overnight fast and four of which did not. Pheochromocytomas were found in 130 patients (67 non-compliant, 63 compliant) and not in 635 patients (195 non-compliant, 440 compliant).

Results: Sampling under non-compliant compared to compliant conditions resulted in 49%, 14% and 51% higher (P<0.001) median plasma concentrations of NMN (84.3 vs 56.5 pg/mL), MN (38.3 vs 33.5 pg/ml) and MTY (18.7 vs 12.4 pg/mL) in patients in whom pheochromocytomas were not found. Upper cutoffs were also higher under non-compliant compared to compliant conditions for NMN (237 vs 144 pg/mL), MN (95.7 vs 80.4 pg/ml) and MTY (70.7 vs 31.0 pg/mL). In contrast, plasma concentrations for NMN, MN and MTY were not higher when sampled under non-compliant versus compliant conditions in patients with pheochromocytoma. Use of upper-cut-offs calculated from data in patients without tumors sampled under non-compliant compared to compliant conditions resulted in substantially decreased diagnostic sensitivity (85.4% vs 97.7%). Use of upper-cut-offs calculated for compliant conditions was associated with a diagnostic specificity of only 71.3% for sampling under non-compliant conditions compared to 93.9% under compliant conditions.

Conclusions: High diagnostic sensitivity of P-NMN/MN/MTY for detection of PPGLs can only be guaranteed using upper-cut-offs of reference intervals appropriately calculated under supine fasting conditions. With appropriately estimated upper-cut-offs, sampling under seated non-fasting conditions can lead to a more than 4-fold increase in false-positive results necessitating repeat sampling under supine fasting conditions.

Nothing to Disclose: RD, MP, CP, KM, AP, MF, FB, AS, SRB, HPN, AJ, JWML, GE

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm