Screening for phaeochromocytoma and paraganglioma: impact of using supine reference intervals for plasma metanephrines with samples collected from fasted/seated patients.

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.

Comparison of the utility of Cocaine- and Amphetamine-Regulated Transcript (CART), chromogranin A, and chromogranin B in neuroendocrine tumor diagnosis and assessment of disease progression.

CONTEXT: Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker. DESIGN AND PARTICIPANTS: Circulating levels of CART peptide and the established NET markers chromogranin A (CgA) and chromogranin B (CgB) were measured using RIA in 353 patients with NET (normal renal function) and in controls. Clinical data were collected retrospectively. MAIN OUTCOME MEASURE(S): The comparative and combined utility of CART, CgA, and CgB for diagnosis and assessment of disease progression was measured in different NET subtypes. RESULTS: CgA and CgB in combination improved diagnostic accuracy in patients with gut NETs, nongastroenteropancreatic NETs, and NETs with an unknown primary origin compared with each biomarker alone. Measuring CART did not further improve diagnosis in these NET subtypes. For pancreatic NETs, CgB was superior to CgA and CART in detecting stable disease (P < .007), whereas CgA and CART in combination were most effective in identifying progressive disease. In phaeochromocytomas/paragangliomas (PCC/PGL), CART was the most useful biomarker for identifying stable (P < .001) and progressive (P = .001) disease. Consistent with this, plasma CART decreased following PCC/PGL tumor resection, remaining low in all patients in remission, but increasing in those with progressive disease. CONCLUSIONS: CART is a useful marker for identifying progressive pancreatic NETs. CART is superior to CgA and CgB in detecting stable and progressive PCC/PGLs, and may have a role as a surveillance marker for PCC/PGL patients.