间甲肾上腺素类物质检测与嗜铬细胞瘤诊断的相关研究
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摘要
目的:观察间甲肾上腺素类物质(MNs)在嗜铬细胞瘤组织及血浆中的表达,评价MNs能否在不同临床类型嗜铬细胞瘤诊断中作为常规检测指标。
方法:以免疫组织化学法了解嗜铬细胞瘤组织中MN表达情况;以ELISA检测血浆游离MNs含量,并与临床资料进行比较分析。
结果:MN在嗜铬细胞瘤组中阳性表达率为75.86%,肾上腺皮质肿瘤组全无表达;嗜铬细胞瘤组血浆MNs诊断敏感性为100%,特异性＞93.18%;其AUC＞0.995,而尿总E及尿总NE的AUC仅有0.842和0.829;非静止型组和静止型组,统计学无显著差异;静止型组的MNs阳性检出率皆为100%。
结论:血浆游离MNs检测应用于嗜铬细胞瘤诊断的敏感性100%;其综合诊断评价明显优于尿肾上腺素和尿去甲肾上腺素;其基本不受临床功能影响,静止型组阳性检出率为100%;因此,血浆游离MNs浓度检测应可以作为诊断嗜铬细胞瘤的理想手段之一。
Aim:To investigate the expression of metanephrine(MN) in the tissue and the plasma free metanephrines(MNs) levels of pheochromocytoma patients for the diagnosis.
Method:Immunohistochemistry was used to detect metanephrine in the tissue samples. Enzyme-linked immunosorbent assay(ELISA) was used to analyse the level of plasma free metanephrine and plasma free normetanephrine(NMN) in these patients' samples.The result was compared with the test data from 24-hour urinary epinephrine(E) and norepinephrine(NE) tests of these patients.
Results:The results of immunochemistry tests on the pheochromocytoma group revealed a positive rate of 75.86%(22/29),however,the adrenocortical disease group did not display any positive result(0/8).ELISA results:The plasma free MNs tests revealed the sensitivity and specificity results of 100%and greater than 93.18%.The area under the receiver operating characteristic(ROC) curve(AUC) of plasma free MNs were greater than 0.995,but the AUC of urinary epinephrine(E) and norepinephrine (NE) were only 0.842 and 0.829.There was no significant statistical difference between the MNs levels of silent pheochromocytoma and non-silent pheochromocytoma groups,two of the pheochromocytoma subgroups(P=0.503, 0.148).The positive detection rate of the silent group was 100%,but the positive detection rates of the 24-hour urinary E and NE tests were 50%and 25%.
Conclusion:(1) The sensitivity and specificity results of plasma free MNs were 100% and greater than 93.18%.(2) Plasma free MNs gave a much better overall evaluation of the diagnosis of pheochromocytoma than the urinary E and NE test did.(3) Plasma free MNs were not affected by different clinical function gradation and the silent pheochromocytoma group revealed a positive detection rate of 100%.
方法:以免疫组织化学法了解嗜铬细胞瘤组织中MN表达情况;以ELISA检测血浆游离MNs含量,并与临床资料进行比较分析。
结果:MN在嗜铬细胞瘤组中阳性表达率为75.86%,肾上腺皮质肿瘤组全无表达;嗜铬细胞瘤组血浆MNs诊断敏感性为100%,特异性＞93.18%;其AUC＞0.995,而尿总E及尿总NE的AUC仅有0.842和0.829;非静止型组和静止型组,统计学无显著差异;静止型组的MNs阳性检出率皆为100%。
结论:血浆游离MNs检测应用于嗜铬细胞瘤诊断的敏感性100%;其综合诊断评价明显优于尿肾上腺素和尿去甲肾上腺素;其基本不受临床功能影响,静止型组阳性检出率为100%;因此,血浆游离MNs浓度检测应可以作为诊断嗜铬细胞瘤的理想手段之一。
Aim:To investigate the expression of metanephrine(MN) in the tissue and the plasma free metanephrines(MNs) levels of pheochromocytoma patients for the diagnosis.
Method:Immunohistochemistry was used to detect metanephrine in the tissue samples. Enzyme-linked immunosorbent assay(ELISA) was used to analyse the level of plasma free metanephrine and plasma free normetanephrine(NMN) in these patients' samples.The result was compared with the test data from 24-hour urinary epinephrine(E) and norepinephrine(NE) tests of these patients.
Results:The results of immunochemistry tests on the pheochromocytoma group revealed a positive rate of 75.86%(22/29),however,the adrenocortical disease group did not display any positive result(0/8).ELISA results:The plasma free MNs tests revealed the sensitivity and specificity results of 100%and greater than 93.18%.The area under the receiver operating characteristic(ROC) curve(AUC) of plasma free MNs were greater than 0.995,but the AUC of urinary epinephrine(E) and norepinephrine (NE) were only 0.842 and 0.829.There was no significant statistical difference between the MNs levels of silent pheochromocytoma and non-silent pheochromocytoma groups,two of the pheochromocytoma subgroups(P=0.503, 0.148).The positive detection rate of the silent group was 100%,but the positive detection rates of the 24-hour urinary E and NE tests were 50%and 25%.
Conclusion:(1) The sensitivity and specificity results of plasma free MNs were 100% and greater than 93.18%.(2) Plasma free MNs gave a much better overall evaluation of the diagnosis of pheochromocytoma than the urinary E and NE test did.(3) Plasma free MNs were not affected by different clinical function gradation and the silent pheochromocytoma group revealed a positive detection rate of 100%.
引文
1. John H, Ziegler WH, Hauri D, et al. Pheochromocytomas: can malignant potential be predicted? Urology. 1999; 53: 679-683.
2. Edstrom Elder E, Hjelm Skog AL, Hoog A, Hamberger B. The management of benign and malignant pheochromocytoma and abdominal paraganglioma. Eur J Surg Oncol. 2003 Apr; 29(3): 278-83
3. Eisenhofer G, Bornstein SR, Brouwers FM. Malignant pheochromocytoma: current status and initiatives for future progress. Endocrine Related Cancer. 2004; 11 (3): 423-436
4. Amar L, Servais A, Gimenez-Roqueplo AP, Zinzindohoue F, Chatellier G, Plouin PF. Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J Clin Endocrinol Metab. 2005 Apr; 90(4): 2110-6. Epub 2005 Jan 11.
5. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW. Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. J Clin Endocrinol Metab. 1998 Jun; 83(6): 2175-85.
6. Eisenhofer G, Huynh TT, Hiroi M, Pacak K. Understanding catecholamine metabolism as a guide to the biochemical diagnosis of pheochromocytoma. Rev Endocr Metab Disord. 2001 Aug; 2(3): 297-311.
7. Raber W, Raffesberg W, Bischof M, Scheuba C, Niederle B, Gasic S, Waldhausl W, Roden M. Diagnostic efficacy of unconjugated plasma metanephrines for the detection of pheochromocytoma. Arch Intern Med. 2000 Oct 23; 160(19): 2957-63.
8. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G.Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002 Mar 20; 287(11): 1427-34.
9. Boyle JG, Davidson DF, Perry CG, Connell JM. Comparison of diagnostic accuracy of urinary free metanephrines, vanillyl mandelic Acid, and catecholamines and plasma catecholamines for diagnosis of pheochromocytoma. J Clin Endocrinol Metab. 2007 Dec; 92(12): 4602-8. Epub 2007 Jul 17.
10. Sawka AM, Prebtani AP, Thabane L, Garni A, Levine M, Young WF Jr. A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma.BMC Endocr Disord.2004 Jun 29;4(1):2.
11.Hoeldtke RD,Israel BC,Cavanaugh ST,Krishna GG.Effect of renal failure on plasma dihydroxyphenylglycol,3-methoxy-4-hydroxyphenylglycol,and vanillymandelic acid.Clin Chim Acta.1989 Sep 29;184(2):195-6.
12.Eisenhofer G,Huysmans F,Pacak K,Walther MM,Sweep FC,Lenders JW.Plasma metanephrines in renal failure.Kidney Int.2005 Feb;67(2):668-77.
13.Lenders JW,Eisenhofer G,Mannelli M,Pacak K.Phaeochromocytoma.Lancet.2005 Aug 20-26;366(9486):665-75.
14.Davidson DF,Grosset K,Grosset D.Parkinson's disease:the effect of L-dopa therapy on urinary free catecholamines and metabolites.Ann Clin Biochem.2007;44:364-368.
15.Willemsen JJ,ROSS HA,Wolthers BG,Sweep CG,Kema IP.Evaluation of specific high-performance liquid-chromatographic determinations of urinary metanephrine and normetanephrine by comparison with isotope dilution mass spectrometry.Ann Clin Biochem.2001 Nov;38(Pt 6):722-30
16.Roden M,Raffesberg W,Raber W,Bernroider E,Niederle B,Waldh(a|¨)usl W,Gasic S.Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen.Clin Chem.2001 Jun;47(6):1061-7.
17.de Jong WH,Graham KS,van der Molen JC,Links TP,Morris MR,Ross HA,de Vries EG,Kema IP.Plasma free metanephrine measurement using automated online solid-phase extraction HPLC tandem mass spectrometry.Clin Chem.2007Sep;53(9):1684-93.
18.Manz B,Kuper M,Booltink E,Fischer-Br(u|¨)gge U.Development of enantioselective immunoassays for free plasma metanephrines.Ann N Y Acad Sci.2004 Jun;1018:582-7.
19.潘东亮,李汉忠,曾正陪.嗜铬细胞瘤临床功能分级与术前准备标准的探讨.中华外科杂志2004年9月第42卷第18期:1089-1092.
20.Eisenhofer G,Huynh TT,Pacak K,Brouwers FM,Walther MM,Linehan WM,et al.Distinct gene expression profiles in norepinephrine-and epinephrine-producing hereditary and sporadic pheochromocytomas:activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome.Endocr Relat Cancer.2004;11:897-911.
21.Eisenhofer G,Lenders JW,Goldstein DS,Mannelli M,Csako G,Walther MM,Brouwers FM,Pacak K.Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines.Clin Chem.2005 Apr;51(4):735-44.
22.Unger N,Pitt C,Schmidt IL,Walz MK,Schmid KW,Philipp T,Mann K,Petersenn S.Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass.Eur J Endoerinol.2006 Mar;154(3):409-17.
23.Copeland PM.The incidentally discovered adrenal mass.Ann Surg.1984 Jan;199(1):116-22
24.鲁功成,张润清,张齐钧,陈晓春,曾甫清.静止嗜铬细胞瘤新概念的探讨.临床泌尿科杂志.1995年第10卷第1期:15-16.
25.Mansmann G,Lau J,Balk E,Rothberg M,Miyachi Y,Bornstein SR.The clinically inapparent adrenal mass:update in diagnosis and management.Endocr Rev.2004Apr;25(2):309-40.
26.Luisa Barzon and Marco Boscaro.Diagnosis and management of adrenal incidentalomas.J Urol.2000;163:398-407.
27.Bravo EL,Tagle R.Pheochromocytoma:state-of-the-art and future prospects.Endocr Rev.2003 Aug;24(4):539-53.
28.石玉玲,胡志恒,毕英俊.尿去甲基肾上腺素/甲氧基肾上腺素测定对嗜铬细胞瘤的方法学比较.生物技术通讯.2006;Vol.17 No.6 Nov:918-919.
29.刘翠萍,唐伟,徐萍等人.尿儿茶酚胺中间代谢产物测定在嗜铬细胞瘤诊断中的应用.实用临床医药杂志.2006年第10卷第5期:104-106.
1.Nakada T,Furuta H,Katayama T.Catecholamine metabolism in pheochromocytoma and normal adrenal medullae.J Urol.1988 Dec;140(6):1348-51.
2.Eisenhofer G,Huynh TT,Hiroi M,Pacak K.Understanding catecholamine metabolism as a guide to the biochemical diagnosis of pheochromocytoma.Rev Endocr Metab Disord.2001 Aug;2(3):297-311.
3.Eisenhofer G,Keiser H,Friberg P,Mezey E,Huynh TT,Hiremagalur B,Ellingson T,Duddempudi S,Eijsbouts A,Lenders JW.Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors.J Clin Endocrinol Metab.1998 Jun;83(6):2175-85.
4.Livett BG.Adrenal medullary chromaffin cells in vitro.Physiol Rev.1984 Oct;64(4):1103-61.
5.Proye C,Fossati P,Fontaine P,Lefebvre J,Decoulx M,Wemeau JL,Dewailly D,Rwamasirabo E,Cecat P.Dopamine-secreting pheochromocytoma:an unrecognized entity? Classification of pheochromocytomas according to their type of secretion.Surgery.1986 Dec;100(6):1154-62.
6.Wong DL,Siddall B J,Ebert SN,Bell RA,Her S.Phenylethanolamine N-methyltransferase gene expression:synergistic activation by Egr-1,AP-2 and the glucocorticoid receptor.Brain Res Mol Brain Res.1998 Oct 30;61(1-2):154-61.
7.Eisenhofer G,Friberg P,Pacak K,Goldstein DS,Murphy DL,Tsigos C,Quyyumi AA,Brunner HG,Lenders JW.Plasma metadrenalines:do they provide useful information about sympatho-adrenal function and catecholamine metabolism?Clin Sci(Lond).1995 May;88(5):533-42
8.Eisenhofer G.Editorial:biochemical diagnosis of pheochromocytoma--is it time to switch to plasma-free metanephrines? J Clin Endocrinol Metab.2003 Feb;88(2):550-2.
9.Omura M,Saito J,Yamaguchi K,Kakuta Y,Nishikawa T.Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan.Hypertens Res.2004 Mar;27(3):193-202.
10.Lenders JW,Eisenhofer G,Mannelli M,Pacak K.Phaeochromocytoma.Lancet.2005 Aug 20-26;366(9486):665-75.
11. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002 Mar 20; 287(11): 1427-34.
12. Sawka AM, Jaeschke R, Singh RJ, Young WF Jr. A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. J Clin Endocrinol Metab. 2003 Feb; 88(2): 553-8.
13. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC. Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative. Ann Intern Med. 2003 Jan 7; 138(1): 40-4.
14. Sawka AM, Prebtani AP, Thabane L, Garni A, Levine M, Young WF Jr. A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma. BMC Endocr Disord. 2004 Jun 29; 4(1): 2.
15. Brain KL, Kay J, Shine B. Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population. Clin Chem. 2006 Nov; 52(11): 2060-4.
16. Unger N, Pitt C, Schmidt IL, Walz MK, Schmid KW, Philipp T, Mann K, Petersenn S. Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. Eur J Endocrinol. 2006 Mar; 154(3): 409-17.
17. Davidson DF. Phaeochromocytoma with normal urinary catecholamines: the potential value of urinary free metadrenalines. Ann Clin Biochem. 2002 Nov; 39(Pt 6): 557-66.
18. Boyle JG, Davidson DF, Perry CG, Connell JM. Comparison of diagnostic accuracy of urinary free metanephrines, vanillyl mandelic Acid, and catecholamines and plasma catecholamines for diagnosis of pheochromocytoma. J Clin Endocrinol Metab. 2007 Dec; 92(12): 4602-8. Epub 2007 Jul 17.
19. Mazza A, Zamboni S, Armigliato M, Zennaro R, Cuppini S, Rempelou P, Rubello D, Pessina AC. Endocrine arterial hypertension: diagnostic approach in clinical practice. Minerva Endocrinol. 2008 Jun; 33(2): 127-46.
20. Weise M, Merke DP, Pacak K, Walther MM, Eisenhofer G. Utility of plasma free metanephrines for detecting childhood pheochromocytoma. J Clin Endocrinol Metab. 2002 May; 87(5): 1955-60.
21. Young WF Jr. Management approaches to adrenal incidentalomas: a view from Rochester, Minnesota. Endocrinol Metab Clin North Am. 2000; 29: 159-85.
22. Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G, Angeli A. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab. 2000; 85: 637-644.
23. Barzon L, Boscaro M. Diagnosis and management of adrenal incidentalomas. J Urol. 2000; 163(2): 398-407.
24. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004 Apr; 25(2): 309-40.
25. Young WF Jr. The Incidentally Discovered Adrenal Mass. N EnglJ Med. 2007; 356: 601-10.
26. Gimm O, Koch CA, Januszewicz A, Opocher G, Neumann HP. The genetic basis of pheochromocytoma. Front Horm Res. 2004; 31: 45-60.
27. Ross JH. Pheochromocytoma. Special considerations in children. Urol Clin North Am. 2000; 27: 393-402.
28. Pacak K, Ilias I, Adams KT, Eisenhofer G. Biochemical diagnosis, localization and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour. J Intern Med. 2005 Jan; 257(1): 60-8.
29. Eisenhofer G, Lenders JW, Linehan WM, Walther MM, Goldstein DS, Keiser HR. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. N EnglJ Med. 1999; 340: 1872-9.
30. Eisenhofer G, Goldstein DS, Sullivan P, Csako G, Brouwers FM, Lai EW, Adams KT, Pacak K. Biochemical and clinical manifestations of dopamine-producing paragangliomas: utility of plasma methoxytyramine. J Clin Endocrinol Metab. 2005 Apr; 90(4): 2068-75. Epub 2005 Jan 11.
31. Eisenhofer G, Lenders JW, Goldstein DS, Mannelli M, Csako G, Walther MM, Brouwers FM, Pacak K. Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines. Clin Chem. 2005 Apr; 51(4): 735-44. Epub 2005 Feb 17.
32. Eisenhofer G, Huynh TT, Pacak K, Brouwers FM, Walther MM, Linehan WM, et al. Distinct gene expression profiles in norepinephrine-and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome. Endocr Relat Cancer. 2004; 11:897-911.
33. Amar L, Baudin E, Burnichon N, Peyrard S, Silvera S, Bertherat J, Bertagna X, Schlumberger M, Jeunemaitre X, Gimenez-Roqueplo AP, Plouin PF. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab. 2007 Oct; 92(10): 3822-8.
34. Grouzmann E, Fathi M, Gillet M, de Torrente A, Cavadas C, Brunner H, Buclin T. Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma. Clin Chem. 2001 Jun; 47(6): 1075-82.
35. Willemsen JJ, Ross HA, Wolthers BG, Sweep CG, Kema IP. Evaluation of specific high-performance liquid-chromatographic determinations of urinary metanephrine and normetanephrine by comparison with isotope dilution mass spectrometry. Ann Clin Biochem. 2001 Nov; 38(Pt 6): 722-30.
36. Wolthers BG, Kema IP, Volmer M, Wesemann R, Westermann J, Manz B. Evaluation of urinary metanephrine and normetanephrine enzyme immunoassay (ELISA) kits by comparison with isotope dilution mass spectrometry. Clin Chem. 1997 Jan; 43(1): 114-20.
37. Roden M, Raffesberg W, Raber W, Bernroider E, Niederle B, Waldhausl W, Gasic S. Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen. Clin Chem. 2001 Jun; 47(6): 1061-7.
38. Lenders JW, Eisenhofer G, Armando I, Keiser HR, Goldstein DS, Kopin IJ. Determination of metanephrines in plasma by liquid chromatography with electrochemical detection. Clin Chem. 1993 Jan; 39(1): 97-103.
39. de Jong WH, Graham KS, van der Molen JC, Links TP, Morris MR, Ross HA, de Vries EG, Kema IP. Plasma free metanephrine measurement using automated online solid-phase extraction HPLC tandem mass spectrometry. Clin Chem. 2007 Sep; 53(9): 1684-93
40. Lagerstedt SA, O'Kane DJ, Singh RJ. Measurement of plasma free metanephrine and normetanephrine by liquid chromatography-tandem mass spectrometry for diagnosis of pheochromocytoma. Clin Chem. 2004 Mar; 50(3): 603-11.
41. Lenz T, Zorner J, Kirchmaier C, Pillitteri D, Badenhoop K, Bartel C, Geiger H, Hasselbacher K, Tuschy U, Westermann J, Salewski L. Multicenter study on the diagnostic value of a new RIA for the detection of free plasma metanephrines in the work-up for pheochromocytoma.Ann N Y Acad Sci.2006 Aug;1073:358-73.
42.Wassell J,Reed P,Kane J,Weinkove C.Freedom from drug interference in new immunoassays for urinary catecholamines and metanephrines.Clin Chem.1999Dec;45(12):2216-23.
43.Manz B,Kuper M,Booltink E,Fischer-Br(u|¨)gge U.Development of enantioselective immunoassays for free plasma metanephrines.Ann N Y Acad Sci.2004 Jun;1018:582-7.
44.Davidson DF,Grosset K,Grosset D.Parkinson's disease:the effect of L-dopa therapy on urinary free catecholamines and metabolites.Ann Clin Biochem.2007;44:364-368.
45.Lenders JW,Willemsen JJ,Eisenhofer G,Ross HA,Pacak K,Timmers HJ,Sweep CG.Is supine rest necessary before blood sampling for plasma metanephrines?Clin Chem.2007 Feb;53(2):352-4.
46.Hoeldtke RD,Israel BC,Cavanaugh ST,Krishna GG.Effect of renal failure on plasma dihydroxyphenylglycol,3-methoxy-4-hydroxyphenylglycol,and vanillymandelic acid.Clin Chim Acta.1989 Sep 29;184(2):195-6.
47.Eiserthofer G,Huysmans F,Pacak K,Walther MM,Sweep FC,Lenders JW.Plasma metanephrines in renal failure.Kidney Int.2005 Feb;67(2):668-77.
2. Edstrom Elder E, Hjelm Skog AL, Hoog A, Hamberger B. The management of benign and malignant pheochromocytoma and abdominal paraganglioma. Eur J Surg Oncol. 2003 Apr; 29(3): 278-83
3. Eisenhofer G, Bornstein SR, Brouwers FM. Malignant pheochromocytoma: current status and initiatives for future progress. Endocrine Related Cancer. 2004; 11 (3): 423-436
4. Amar L, Servais A, Gimenez-Roqueplo AP, Zinzindohoue F, Chatellier G, Plouin PF. Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J Clin Endocrinol Metab. 2005 Apr; 90(4): 2110-6. Epub 2005 Jan 11.
5. Eisenhofer G, Keiser H, Friberg P, Mezey E, Huynh TT, Hiremagalur B, Ellingson T, Duddempudi S, Eijsbouts A, Lenders JW. Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors. J Clin Endocrinol Metab. 1998 Jun; 83(6): 2175-85.
6. Eisenhofer G, Huynh TT, Hiroi M, Pacak K. Understanding catecholamine metabolism as a guide to the biochemical diagnosis of pheochromocytoma. Rev Endocr Metab Disord. 2001 Aug; 2(3): 297-311.
7. Raber W, Raffesberg W, Bischof M, Scheuba C, Niederle B, Gasic S, Waldhausl W, Roden M. Diagnostic efficacy of unconjugated plasma metanephrines for the detection of pheochromocytoma. Arch Intern Med. 2000 Oct 23; 160(19): 2957-63.
8. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G.Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002 Mar 20; 287(11): 1427-34.
9. Boyle JG, Davidson DF, Perry CG, Connell JM. Comparison of diagnostic accuracy of urinary free metanephrines, vanillyl mandelic Acid, and catecholamines and plasma catecholamines for diagnosis of pheochromocytoma. J Clin Endocrinol Metab. 2007 Dec; 92(12): 4602-8. Epub 2007 Jul 17.
10. Sawka AM, Prebtani AP, Thabane L, Garni A, Levine M, Young WF Jr. A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma.BMC Endocr Disord.2004 Jun 29;4(1):2.
11.Hoeldtke RD,Israel BC,Cavanaugh ST,Krishna GG.Effect of renal failure on plasma dihydroxyphenylglycol,3-methoxy-4-hydroxyphenylglycol,and vanillymandelic acid.Clin Chim Acta.1989 Sep 29;184(2):195-6.
12.Eisenhofer G,Huysmans F,Pacak K,Walther MM,Sweep FC,Lenders JW.Plasma metanephrines in renal failure.Kidney Int.2005 Feb;67(2):668-77.
13.Lenders JW,Eisenhofer G,Mannelli M,Pacak K.Phaeochromocytoma.Lancet.2005 Aug 20-26;366(9486):665-75.
14.Davidson DF,Grosset K,Grosset D.Parkinson's disease:the effect of L-dopa therapy on urinary free catecholamines and metabolites.Ann Clin Biochem.2007;44:364-368.
15.Willemsen JJ,ROSS HA,Wolthers BG,Sweep CG,Kema IP.Evaluation of specific high-performance liquid-chromatographic determinations of urinary metanephrine and normetanephrine by comparison with isotope dilution mass spectrometry.Ann Clin Biochem.2001 Nov;38(Pt 6):722-30
16.Roden M,Raffesberg W,Raber W,Bernroider E,Niederle B,Waldh(a|¨)usl W,Gasic S.Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen.Clin Chem.2001 Jun;47(6):1061-7.
17.de Jong WH,Graham KS,van der Molen JC,Links TP,Morris MR,Ross HA,de Vries EG,Kema IP.Plasma free metanephrine measurement using automated online solid-phase extraction HPLC tandem mass spectrometry.Clin Chem.2007Sep;53(9):1684-93.
18.Manz B,Kuper M,Booltink E,Fischer-Br(u|¨)gge U.Development of enantioselective immunoassays for free plasma metanephrines.Ann N Y Acad Sci.2004 Jun;1018:582-7.
19.潘东亮,李汉忠,曾正陪.嗜铬细胞瘤临床功能分级与术前准备标准的探讨.中华外科杂志2004年9月第42卷第18期:1089-1092.
20.Eisenhofer G,Huynh TT,Pacak K,Brouwers FM,Walther MM,Linehan WM,et al.Distinct gene expression profiles in norepinephrine-and epinephrine-producing hereditary and sporadic pheochromocytomas:activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome.Endocr Relat Cancer.2004;11:897-911.
21.Eisenhofer G,Lenders JW,Goldstein DS,Mannelli M,Csako G,Walther MM,Brouwers FM,Pacak K.Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines.Clin Chem.2005 Apr;51(4):735-44.
22.Unger N,Pitt C,Schmidt IL,Walz MK,Schmid KW,Philipp T,Mann K,Petersenn S.Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass.Eur J Endoerinol.2006 Mar;154(3):409-17.
23.Copeland PM.The incidentally discovered adrenal mass.Ann Surg.1984 Jan;199(1):116-22
24.鲁功成,张润清,张齐钧,陈晓春,曾甫清.静止嗜铬细胞瘤新概念的探讨.临床泌尿科杂志.1995年第10卷第1期:15-16.
25.Mansmann G,Lau J,Balk E,Rothberg M,Miyachi Y,Bornstein SR.The clinically inapparent adrenal mass:update in diagnosis and management.Endocr Rev.2004Apr;25(2):309-40.
26.Luisa Barzon and Marco Boscaro.Diagnosis and management of adrenal incidentalomas.J Urol.2000;163:398-407.
27.Bravo EL,Tagle R.Pheochromocytoma:state-of-the-art and future prospects.Endocr Rev.2003 Aug;24(4):539-53.
28.石玉玲,胡志恒,毕英俊.尿去甲基肾上腺素/甲氧基肾上腺素测定对嗜铬细胞瘤的方法学比较.生物技术通讯.2006;Vol.17 No.6 Nov:918-919.
29.刘翠萍,唐伟,徐萍等人.尿儿茶酚胺中间代谢产物测定在嗜铬细胞瘤诊断中的应用.实用临床医药杂志.2006年第10卷第5期:104-106.
1.Nakada T,Furuta H,Katayama T.Catecholamine metabolism in pheochromocytoma and normal adrenal medullae.J Urol.1988 Dec;140(6):1348-51.
2.Eisenhofer G,Huynh TT,Hiroi M,Pacak K.Understanding catecholamine metabolism as a guide to the biochemical diagnosis of pheochromocytoma.Rev Endocr Metab Disord.2001 Aug;2(3):297-311.
3.Eisenhofer G,Keiser H,Friberg P,Mezey E,Huynh TT,Hiremagalur B,Ellingson T,Duddempudi S,Eijsbouts A,Lenders JW.Plasma metanephrines are markers of pheochromocytoma produced by catechol-O-methyltransferase within tumors.J Clin Endocrinol Metab.1998 Jun;83(6):2175-85.
4.Livett BG.Adrenal medullary chromaffin cells in vitro.Physiol Rev.1984 Oct;64(4):1103-61.
5.Proye C,Fossati P,Fontaine P,Lefebvre J,Decoulx M,Wemeau JL,Dewailly D,Rwamasirabo E,Cecat P.Dopamine-secreting pheochromocytoma:an unrecognized entity? Classification of pheochromocytomas according to their type of secretion.Surgery.1986 Dec;100(6):1154-62.
6.Wong DL,Siddall B J,Ebert SN,Bell RA,Her S.Phenylethanolamine N-methyltransferase gene expression:synergistic activation by Egr-1,AP-2 and the glucocorticoid receptor.Brain Res Mol Brain Res.1998 Oct 30;61(1-2):154-61.
7.Eisenhofer G,Friberg P,Pacak K,Goldstein DS,Murphy DL,Tsigos C,Quyyumi AA,Brunner HG,Lenders JW.Plasma metadrenalines:do they provide useful information about sympatho-adrenal function and catecholamine metabolism?Clin Sci(Lond).1995 May;88(5):533-42
8.Eisenhofer G.Editorial:biochemical diagnosis of pheochromocytoma--is it time to switch to plasma-free metanephrines? J Clin Endocrinol Metab.2003 Feb;88(2):550-2.
9.Omura M,Saito J,Yamaguchi K,Kakuta Y,Nishikawa T.Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan.Hypertens Res.2004 Mar;27(3):193-202.
10.Lenders JW,Eisenhofer G,Mannelli M,Pacak K.Phaeochromocytoma.Lancet.2005 Aug 20-26;366(9486):665-75.
11. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, Keiser HR, Goldstein DS, Eisenhofer G. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002 Mar 20; 287(11): 1427-34.
12. Sawka AM, Jaeschke R, Singh RJ, Young WF Jr. A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. J Clin Endocrinol Metab. 2003 Feb; 88(2): 553-8.
13. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC. Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative. Ann Intern Med. 2003 Jan 7; 138(1): 40-4.
14. Sawka AM, Prebtani AP, Thabane L, Garni A, Levine M, Young WF Jr. A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma. BMC Endocr Disord. 2004 Jun 29; 4(1): 2.
15. Brain KL, Kay J, Shine B. Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population. Clin Chem. 2006 Nov; 52(11): 2060-4.
16. Unger N, Pitt C, Schmidt IL, Walz MK, Schmid KW, Philipp T, Mann K, Petersenn S. Diagnostic value of various biochemical parameters for the diagnosis of pheochromocytoma in patients with adrenal mass. Eur J Endocrinol. 2006 Mar; 154(3): 409-17.
17. Davidson DF. Phaeochromocytoma with normal urinary catecholamines: the potential value of urinary free metadrenalines. Ann Clin Biochem. 2002 Nov; 39(Pt 6): 557-66.
18. Boyle JG, Davidson DF, Perry CG, Connell JM. Comparison of diagnostic accuracy of urinary free metanephrines, vanillyl mandelic Acid, and catecholamines and plasma catecholamines for diagnosis of pheochromocytoma. J Clin Endocrinol Metab. 2007 Dec; 92(12): 4602-8. Epub 2007 Jul 17.
19. Mazza A, Zamboni S, Armigliato M, Zennaro R, Cuppini S, Rempelou P, Rubello D, Pessina AC. Endocrine arterial hypertension: diagnostic approach in clinical practice. Minerva Endocrinol. 2008 Jun; 33(2): 127-46.
20. Weise M, Merke DP, Pacak K, Walther MM, Eisenhofer G. Utility of plasma free metanephrines for detecting childhood pheochromocytoma. J Clin Endocrinol Metab. 2002 May; 87(5): 1955-60.
21. Young WF Jr. Management approaches to adrenal incidentalomas: a view from Rochester, Minnesota. Endocrinol Metab Clin North Am. 2000; 29: 159-85.
22. Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G, Angeli A. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. J Clin Endocrinol Metab. 2000; 85: 637-644.
23. Barzon L, Boscaro M. Diagnosis and management of adrenal incidentalomas. J Urol. 2000; 163(2): 398-407.
24. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004 Apr; 25(2): 309-40.
25. Young WF Jr. The Incidentally Discovered Adrenal Mass. N EnglJ Med. 2007; 356: 601-10.
26. Gimm O, Koch CA, Januszewicz A, Opocher G, Neumann HP. The genetic basis of pheochromocytoma. Front Horm Res. 2004; 31: 45-60.
27. Ross JH. Pheochromocytoma. Special considerations in children. Urol Clin North Am. 2000; 27: 393-402.
28. Pacak K, Ilias I, Adams KT, Eisenhofer G. Biochemical diagnosis, localization and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour. J Intern Med. 2005 Jan; 257(1): 60-8.
29. Eisenhofer G, Lenders JW, Linehan WM, Walther MM, Goldstein DS, Keiser HR. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. N EnglJ Med. 1999; 340: 1872-9.
30. Eisenhofer G, Goldstein DS, Sullivan P, Csako G, Brouwers FM, Lai EW, Adams KT, Pacak K. Biochemical and clinical manifestations of dopamine-producing paragangliomas: utility of plasma methoxytyramine. J Clin Endocrinol Metab. 2005 Apr; 90(4): 2068-75. Epub 2005 Jan 11.
31. Eisenhofer G, Lenders JW, Goldstein DS, Mannelli M, Csako G, Walther MM, Brouwers FM, Pacak K. Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines. Clin Chem. 2005 Apr; 51(4): 735-44. Epub 2005 Feb 17.
32. Eisenhofer G, Huynh TT, Pacak K, Brouwers FM, Walther MM, Linehan WM, et al. Distinct gene expression profiles in norepinephrine-and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel-Lindau syndrome. Endocr Relat Cancer. 2004; 11:897-911.
33. Amar L, Baudin E, Burnichon N, Peyrard S, Silvera S, Bertherat J, Bertagna X, Schlumberger M, Jeunemaitre X, Gimenez-Roqueplo AP, Plouin PF. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab. 2007 Oct; 92(10): 3822-8.
34. Grouzmann E, Fathi M, Gillet M, de Torrente A, Cavadas C, Brunner H, Buclin T. Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma. Clin Chem. 2001 Jun; 47(6): 1075-82.
35. Willemsen JJ, Ross HA, Wolthers BG, Sweep CG, Kema IP. Evaluation of specific high-performance liquid-chromatographic determinations of urinary metanephrine and normetanephrine by comparison with isotope dilution mass spectrometry. Ann Clin Biochem. 2001 Nov; 38(Pt 6): 722-30.
36. Wolthers BG, Kema IP, Volmer M, Wesemann R, Westermann J, Manz B. Evaluation of urinary metanephrine and normetanephrine enzyme immunoassay (ELISA) kits by comparison with isotope dilution mass spectrometry. Clin Chem. 1997 Jan; 43(1): 114-20.
37. Roden M, Raffesberg W, Raber W, Bernroider E, Niederle B, Waldhausl W, Gasic S. Quantification of unconjugated metanephrines in human plasma without interference by acetaminophen. Clin Chem. 2001 Jun; 47(6): 1061-7.
38. Lenders JW, Eisenhofer G, Armando I, Keiser HR, Goldstein DS, Kopin IJ. Determination of metanephrines in plasma by liquid chromatography with electrochemical detection. Clin Chem. 1993 Jan; 39(1): 97-103.
39. de Jong WH, Graham KS, van der Molen JC, Links TP, Morris MR, Ross HA, de Vries EG, Kema IP. Plasma free metanephrine measurement using automated online solid-phase extraction HPLC tandem mass spectrometry. Clin Chem. 2007 Sep; 53(9): 1684-93
40. Lagerstedt SA, O'Kane DJ, Singh RJ. Measurement of plasma free metanephrine and normetanephrine by liquid chromatography-tandem mass spectrometry for diagnosis of pheochromocytoma. Clin Chem. 2004 Mar; 50(3): 603-11.
41. Lenz T, Zorner J, Kirchmaier C, Pillitteri D, Badenhoop K, Bartel C, Geiger H, Hasselbacher K, Tuschy U, Westermann J, Salewski L. Multicenter study on the diagnostic value of a new RIA for the detection of free plasma metanephrines in the work-up for pheochromocytoma.Ann N Y Acad Sci.2006 Aug;1073:358-73.
42.Wassell J,Reed P,Kane J,Weinkove C.Freedom from drug interference in new immunoassays for urinary catecholamines and metanephrines.Clin Chem.1999Dec;45(12):2216-23.
43.Manz B,Kuper M,Booltink E,Fischer-Br(u|¨)gge U.Development of enantioselective immunoassays for free plasma metanephrines.Ann N Y Acad Sci.2004 Jun;1018:582-7.
44.Davidson DF,Grosset K,Grosset D.Parkinson's disease:the effect of L-dopa therapy on urinary free catecholamines and metabolites.Ann Clin Biochem.2007;44:364-368.
45.Lenders JW,Willemsen JJ,Eisenhofer G,Ross HA,Pacak K,Timmers HJ,Sweep CG.Is supine rest necessary before blood sampling for plasma metanephrines?Clin Chem.2007 Feb;53(2):352-4.
46.Hoeldtke RD,Israel BC,Cavanaugh ST,Krishna GG.Effect of renal failure on plasma dihydroxyphenylglycol,3-methoxy-4-hydroxyphenylglycol,and vanillymandelic acid.Clin Chim Acta.1989 Sep 29;184(2):195-6.
47.Eiserthofer G,Huysmans F,Pacak K,Walther MM,Sweep FC,Lenders JW.Plasma metanephrines in renal failure.Kidney Int.2005 Feb;67(2):668-77.