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|Date/Time:||Thursday April 25, 2013
830 BC/ 930 AB & SK/ 1030 MB /1130 ON & QC/ 1230 NS & NB/ 1300 NL
|Topic:||Advances and Biochemical Testing in Pheochromocytoma|
|Speaker:||Ravinder J. Singh PhD
Clinical Biochemistry and Immunology, Mayo Clinic, Rochester Minnesota
Pheochromocytoma being a rare disease needs a specific test but also being fatal and curable would ask for a sensitive test. In comparison to plasma free metanephrines, catecholamines, VMA, and total metanephrines have been reported to be less sensitive and specific for diagnosis of pheochromocytoma. However, in another recent study the combined specificity of the of total metanephrines and urine catecholamines has been reported to be higher than plasma free metanephrines. In both studies the high pressure liquid chromatography electrochemical (HPLC-EC) with solid phase extraction methodology has been used for plasma free metanephrines. HPLC also allows the fractionation of urine metanephrines into normetanephrine and metanephrines and has replaced the colorimetric method for total metanephrines. This method is esoteric, labor intensive, has low throughput and is prone to interferences of medications used for the management of hypertension. We have recently developed a sensitive and specific method using state of the art LC-MS/MS methodology for the determination of metanephrine and normetanephrines in both plasma and urine. This test in urine like plasma is 100 % sensitive when calculated based on age and gender specific reference ranges. By determining the levels of urine metanephrines and normetanephrines in hypertensives (non pheos) we have determined the clinical cut off values for NMN and MN to be 900 ug/24h and 400 ug/24 hr respectively. We have confirmed this with a limited number (N=18) of confirmed pheo patients and have achieved 100 % specificity for urine test without a major loss in sensitivity. In comparison to conjugated metanephrines in urine the circulating concentrations of free normetanephrines in plasma are much lower [< 0.9 nmol/L (160 pg/ml)]. The cut off of 2.2 nmol/L (400 pg/ml) has been reported recently to provide 100 % specificity for diagnosis of pheochromocytoma. Similarly the circulating concentration of free metanephrines are less than 0.5 nmol/L (100 pg/ml) and cut off of 1.6 nmol/L (320 pg/ml) has been reported to provide 100 % specificity. There are advantages and disadvantages of having single plasma or the urine as the first test of choice and it is possible both specimens may be required for the confirmation of the diagnosis of pheochromocytoma. Chromatographic determination of metanephrines provide a sensitive test and the use of single gold standard methodology in one laboratory will allow us to compare the specificity of the plasma and urine metanephrines as this was reported to one of the limitations of the previous studies.
At the end of this session, participants will be able to:
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