scholarly journals Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma

Author(s):  
G. Eisenhofer ◽  
P. Lattke ◽  
M. Herberg ◽  
G. Siegert ◽  
N. Qin ◽  
...  
Author(s):  
R Casey ◽  
TP Griffin ◽  
D Wall ◽  
MC Dennedy ◽  
M Bell ◽  
...  

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.


2020 ◽  
Vol 30 (2) ◽  
pp. 325-330
Author(s):  
Caroline M Joyce ◽  
Audrey Melvin ◽  
Paula M O’Shea ◽  
Seán J Costelloe ◽  
Domhnall J O’Halloran

Plasma free metanephrines or urinary fractionated metanephrines are the biochemical tests of choice for the diagnosis of pheochromocytoma as they have greater sensitivity and specificity than catecholamines for pheochromocytoma detection. This case highlights the preanalytical factors which can influence metanephrine measurement and cause a false positive result. It describes a patient with a high pre-test probability of pheochromocytoma due to hypertension and a past medical history of adrenalectomy for a purported pheochromocytoma in her home country. When biochemical screening revealed grossly elevated urine normetanephrine in the presence of a previously identified right adrenal lesion, there was high clinical suspicion of a pheochromocytoma. However, functional imaging did not support this view which prompted additional testing with plasma metanephrines. Results for plasma and urine metanephrines were discordant and preanalytical drug interference was suspected. Patient medications were reviewed and sulfasalazine, an anti-inflammatory drug was identified as the most likely analytical interferent. Urinary fractionated metanephrines were re-analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS) and all metanephrines were within their reference intervals. This case illustrates how method-specific analytical drug interference prompted unnecessary expensive imaging, heightened patient anxiety and resulted in lengthy investigations for what turned out to be a phantom pheochromocytoma.


2018 ◽  
Vol 57 (1) ◽  
pp. 1-11
Author(s):  
Robert Flatman

Abstract Harmonization initiatives in laboratory medicine seek to eliminate or reduce illogical variations in service to patients, clinicians and other healthcare professionals. Significant effort will be required to achieve consistent application of terminology, units and reporting across laboratory testing providers. Current variations in practice for nomenclature, reference intervals, flagging, units, standardization and traceability between analytical methods, and presentation of cumulative result data are inefficient and inconvenient, or worse yet, patient safety risks. All aspects of laboratory service across the “total testing process” ultimately depend on concise, reliable communication. Clinical terminologies (e.g. SNOMED-CT, LOINC, IFCC/IUPAC NPU) provide a mechanism to correctly identify an analyte or panel of tests within a request for testing and communicate the results back to the clinician or electronic health record (EHR). Electronic systems for requesting and reporting laboratory testing are said to be interoperable when reliable connection and communication of content occur. Modern electronic reports and EHRs will provide greater flexibility and functionality, but also require effective guidelines or standards to ensure consistent representation of laboratory data. Programs to harmonize service in these areas require ongoing local, national and international efforts and should incorporate stakeholders from laboratories, medical staff, information technology and informatics specialists, patient representatives and government. The process of identifying harmonized best practice, then ensuring uptake across many laboratory testing providers, is generally iterative rather than “one off”. New opportunities for additional harmonization will be generated as analytical performance, standardization and traceability, and diagnosis and treatment continue to evolve.


2018 ◽  
Vol 149 (suppl_1) ◽  
pp. S174-S174 ◽  
Author(s):  
Robert M Humble ◽  
Matthew D Krasowski

2018 ◽  
Vol 72 (6) ◽  
pp. 907-909 ◽  
Author(s):  
Christina Pamporaki ◽  
Aleksander Prejbisz ◽  
Robert Małecki ◽  
Frank Pistrosch ◽  
Mirko Peitzsch ◽  
...  

2014 ◽  
Vol 60 (12) ◽  
pp. 1486-1499 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Mirko Peitzsch

Abstract BACKGROUND Pheochromocytomas and paragangliomas (PPGLs) are potentially lethal yet usually surgically curable causes of endocrine hypertension; therefore, once clinical suspicion is aroused it is imperative that clinicians choose the most appropriate laboratory tests to identify the tumors. CONTENT Compelling evidence now indicates that initial screening for PPGLs should include measurements of plasma free metanephrines or urine fractionated metanephrines. LC-MS/MS offers numerous advantages over other analytical methods and is the method of choice when measurements include methoxytyramine, the O-methylated metabolite of dopamine. The plasma test offers advantages over the urine test, although it is rarely implemented correctly, rendering the urine test preferable for mainstream use. To ensure optimum diagnostic sensitivity for the plasma test, reference intervals must be established for blood samples collected after 30 min of supine rest and after an overnight fast when measurements include methoxytyramine. Similarly collected blood samples during screening, together with use of age-adjusted reference intervals, further minimize false-positive results. Extents and patterns of increases in plasma normetanephrine, metanephrine, and methoxytyramine can additionally help predict size and adrenal vs extraadrenal locations of tumors, as well as presence of metastases and underlying germline mutations of tumor susceptibility genes. SUMMARY Carried out correctly at specialist endocrine centers, collection of blood for measurements of plasma normetanephrine, metanephrine, and methoxytyramine not only provides high accuracy for diagnosis of PPGLs, but can also guide clinical decision-making about follow-up imaging strategies, genetic testing, and therapeutic options. At other centers, measurements of urine fractionated metanephrines will identify most PPGLs.


2016 ◽  
Vol 21 (2) ◽  
pp. 3-8
Author(s):  
Seth D. Cohen ◽  
Steven Mandel ◽  
David B. Samadi

Abstract To properly assess men and women with sexual dysfunction, evaluators should take a biopsychosocial approach that may require consultation with multiple health care professionals from various fields in order to get to the root of the sexual dysfunction; this multidisciplinary methodology offers the best chance of successful treatment. For males, this article focuses on erectile dysfunction (ED) and hypogonadism. The initial evaluation of ED involves a thorough case history, preferably taken from the patient and partner, physical examination, and proper laboratory and diagnostic tests, including an acknowledgment of the subjective complaint. The diagnosis is established on the basis of an individual's report of the consistent inability to attain and maintain an erection sufficient to permit satisfactory sexual intercourse. Initial workups for ED should entail a detailed history that can be obtained from a validated questionnaire such as the International Index of Erectile Function and the Sexual Health Inventory for Men. Hypogonadism is evaluated using the validated Androgen Deficiency in the Aging Male questionnaire and laboratory testing for testosterone deficiency. Treatments logically can begin with the least invasive and then progress to more invasive strategies after appropriate counseling. The last and most important treatment component when caring for men with sexual dysfunction—and, arguably, the least practiced—is close follow-up.


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