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Supine or sitting? Economic considerations regarding patient position during plasma metanephrine analysis for the exclusion of chromaffin tumours

Dear Editor, We have read the article ‘Biochemical diagnosis of phaeochromocytoma using plasma-free normetanephrine, metanephrine and methoxytyramine: importance of supine sampling under fasting conditions’ by Darr et al. with great interest. We concur with the importance of using reference ranges derived from supine, fasting patients to ensure a high diagnostic sensitivity for the detection of phaeochromocytomas/paragangliomas (PPGL). However, despite the demonstrated improved specificity, we believe that adopting measurement of plasma metanephrines in fasted patients in the supine position as a first-line diagnostic screening approach would not be practical in modern healthcare provision due to its substantial financial implications. We reviewed all plasma metanephrine results from patients requiring exclusion of PPGL due to presentation with a new adrenal lesion (n = 55) who attended our service at the University Hospital Birmingham during 2013. The vast majority of cases were adrenal incidentalomas (n = 48); in the remainder, the lesion was discovered in the context of regular monitoring for succinate dehydrogenase (SDH) or von Hippel–Lindau (VHL) gene mutations (n = 3), work-up for Cushing’s syndrome (n = 2) or postoperative follow-up imaging of previous extra-adrenal malignancy (n = 2). According to our local protocol, these patients are screened for PPGL with one plasma sample for metanephrines taken without special preparation, in the nonfasted state and sitting position on the day of their first clinic attendance. If plasma metanephrines determined under these conditions are elevated, repeat testing in the fasting state and after 30 min in the supine position is arranged by the endocrine specialist nurses. Of the 55 patients tested, seven (13%) had positive test results under sitting/ nonfasting conditions, that is increased above a reference range derived from healthy controls with samples collected in the supine/fasted state. Three of seven with plasma normetanephrine and/or metanephrine values >4-fold of the reference range were conclusively diagnosed with PPGL and not retested. The four remaining patients underwent repeat testing under supine/fasting conditions, revealing persistently increased plasma metanephrines in three of them, eventually diagnosed with phaeochromocytoma. Only one patient with borderline elevated plasma metanephrines in the sitting/nonfasting state was confirmed to have had a falsepositive result on initial screening, with the repeat test under supine/fasting conditions demonstrating normal plasma metanephrines (Table 1). Our screening under sitting/nonfasted conditions yielded a sensitivity of 86% (due to one case of a nonsecreting paraganglioma) and specificity of 98% for diagnosing chromaffin tumours; the overall prevalence of PPGL in our population was 11%. Blood samples for plasma metanephrines in the sitting and nonfasting state can be conveniently collected in the context of the first outpatient clinic visit and incurs a cost of £40 (£38 for biochemical analysis plus £2 phlebotomy costs). Conversely, supine/fasting sampling requires an extra visit to a nurse-led endocrinology outpatient clinic as a hospital day case, which incurs a total cost of £583 (£545 day case cost plus £38 for biochemical analysis). The overall cost of plasma metanephrine testing for the year 2013 in our department amounted to £4532. Adopting supine/fasting sampling as first-line investigation in all patients would inflate the total annual cost to £32 065, accruing an additional expenditure of £27 533. We acknowledge the fact that the cost of supine sampling may vary significantly from centre to centre but it would always exceed the cost of routine phlebotomy carried out in a one-stop approach during the routine clinic visit. Consequently, the strategy we propose will be