title: Screening for phaeochromocytoma and paraganglioma: impact of using supine reference intervals for plasma metanephrines with samples collected from fasted/seated patients.
abstract: Background The Endocrine Society Clinical Practice Guideline on Phaeochomocytoma and Paraganglioma recommends phlebotomy for plasma-free metanephrines with patients fasted and supine using appropriately defined reference intervals. Studies have shown higher diagnostic sensitivities using these criteria. Further, with seated-sampling protocols, for result interpretation, reference intervals that do not compromise diagnostic sensitivity should be employed. Objective To determine the impact on diagnostic performance and financial cost of using supine reference intervals for result interpretation with our current plasma-free metanephrines fasted/seated-sampling protocol. Methods We conducted a retrospective cohort study of patients who underwent screening for PPGL using plasma-free metanephrines from 2009 to 2014 at Galway University Hospitals. Plasma-free metanephrines were measured using liquid chromatography-tandem mass spectrometry. Supine thresholds for plasma normetanephrine and metanephrine set at 610 pmol/L and 310 pmol/L, respectively, were used. Results A total of 183 patients were evaluated. Mean age of participants was 53.4 (±16.3) years. Five of 183 (2.7%) patients had histologically confirmed PPGL (males, n=4). Using seated reference intervals for plasma-free metanephrines, diagnostic sensitivity and specificity were 100% and 98.9%, respectively, with two false-positive cases. Application of reference intervals established in subjects supine and fasted to this cohort gave diagnostic sensitivity of 100% with specificity of 74.7%. Financial analysis of each pretesting strategy demonstrated cost-equivalence (€147.27/patient). Conclusion Our cost analysis, together with the evidence that fasted/supine-sampling for plasma-free metanephrines, offers more reliable exclusion of PPGL mandates changing our current practice. This study highlights the important advantages of standardized diagnostic protocols for plasma-free metanephrines to ensure the highest diagnostic accuracy for investigation of PPGL.
authors.affiliation: 1 Department of Endocrinology, Centre of Diabetes, Endocrinology and Metabolism, Galway University Hospitals & Saolta Hospital Group, Galway, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Casey
authors.affiliation: 1 Department of Endocrinology, Centre of Diabetes, Endocrinology and Metabolism, Galway University Hospitals & Saolta Hospital Group, Galway, Ireland.
authors.forename: T P
authors.initials: TP
authors.lastname: Griffin
authors.affiliation: 2 School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Wall
authors.affiliation: 1 Department of Endocrinology, Centre of Diabetes, Endocrinology and Metabolism, Galway University Hospitals & Saolta Hospital Group, Galway, Ireland.|3 Discipline of Pharmacology & Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland.
authors.forename: M C
authors.initials: MC
authors.lastname: Dennedy
authors.affiliation: 1 Department of Endocrinology, Centre of Diabetes, Endocrinology and Metabolism, Galway University Hospitals & Saolta Hospital Group, Galway, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Bell
authors.affiliation: 4 Department of Clinical Biochemistry, Galway University Hospitals & Saolta Hospital Group, Galway, Ireland.
authors.forename: P M
authors.initials: PM
authors.lastname: O'Shea
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002853:Chromatography, Liquid / Q000191:economics; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood*; D008875:Middle Aged; D010235:Paraganglioma / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D056888:Patient Positioning / Q000379:methods; D010673:Pheochromocytoma / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D011187:Posture; D017410:Practice Guidelines as Topic; D012016:Reference Values; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016683:Supine Position; D053719:Tandem Mass Spectrometry / Q000191:economics
chemical_list: D014408:Biomarkers, Tumor; D008676:Metanephrine
keywords: Phaeochromocytoma; adrenal medulla hormones; paraganglioma