Familial Cancer

, Volume 4, Issue 1, pp 25–36 | Cite as

Multiple endocrine neoplasia type 2

  • Mariola Peczkowska
  • Andrzej Januszewicz


Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant inherited cancer syndrome. Predisposition to MEN 2 is caused by germline mutations of the RET proto-oncogene on chromosome 10q11.2 [1]. There are three clinically distinct forms of MEN 2 syndrome – MEN 2A, familial medullary thyroid carcinoma (FMTC), and MEN 2B. In all of these subtypes, medullary thyroid carcinoma (MTC) is a key. MEN 2A is the most common subtype of MEN 2. Clinical features of the MEN 2A syndrome include medullary thyroid carcinoma (MTC) and/or C-cell hyperplasia (CCH) in almost all affected individuals, pheochromocytoma (approximately 50%) and hyperparathyroidism (HPT) (15–30%). MEN type 2B is the most aggressive of the MEN 2 variants and accounts for approximately 5% of all cases of MEN 2. MEN 2B is similar to MEN 2A but is characterized by the earlier onset of the disease and by developmental abnormalities. In FMTC, the third form of MEN 2, MTC is the only clinical feature. Introduced in recent years and still developing genetic testing of individuals at highest hereditary risk of MEN 2 syndrome holds the possibility of early detection and improved treatment and prognosis.


MEN 2 medullary thyroid carcinoma pheochromocytoma RET 


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  1. 1.
    Mathew, CGP, Chin, KS, Easton, DF,  et al. 1987A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10Nature12852730CrossRefGoogle Scholar
  2. 2.
    Eng, C 1996The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung’s diseaseN Engl J Med33594351CrossRefPubMedGoogle Scholar
  3. 3.
    Opocher, G, Sciavi, F, Conton, P,  et al. 2003Clinical and genetic aspects of pheochromocytomaHorn Res59(Suppl 1)5661CrossRefGoogle Scholar
  4. 4.
    Neumann, HPH, Berger, DP, Sigmund, G,  et al. 1993Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau diseaseN Engl J Med32915318CrossRefPubMedGoogle Scholar
  5. 5.
    Eng, C, Hampel, H, Chapelle, A 2000Genetic testing for cancer predispositionAnn Rev Med52371400CrossRefGoogle Scholar
  6. 6.
    Cohen, MS, Phay, JE, Albinson, C,  et al. 2002Gastrointestinal manifestations of multiple endocrine neoplasia type 2Ann Surg23564855CrossRefPubMedGoogle Scholar
  7. 7.
    Gimm, O 2001Multiple endocrine neoplasia type 2: clinical aspectsFront Horm Res2810330PubMedGoogle Scholar
  8. 8.
    Brandi, ML, Gagel, RF, Angeli, A,  et al. 2001Consensus. Guidelines for diagnosis and therapy of MEN type 1 and type 2J Clin Endocrinol Metab86565871Google Scholar
  9. 9.
    Casanova, S, Rosenberg-Bourgin, M, Farkas, D,  et al. 1993Pheochromocytoma in multiple endocrine neoplasia type 2A: survey of 100 casesClin Endocrinol385317Google Scholar
  10. 10.
    Dotzenrath, C, Cupisti, K, Goretzki, PE,  et al. 2001Long-term biochemical results after operative treatment of primary hyperparathyroidism associated with multiple endocrine neoplasia type I and IIa: is a more or less extended operation essentialEur J Surg1671738CrossRefPubMedGoogle Scholar
  11. 11.
    Schuffenecker, I, Virally-Monod, M, Brohet, R,  et al. 1998Risk and penetrance of primary hyperparathyroidism in multiple endocrine neoplasia type 2A families with mutations at codon 634 of the RET proto-oncogeneJ Clin Endocrinol Metab8348791CrossRefPubMedGoogle Scholar
  12. 12.
    Zedenius, J, Larsson, C, Bergholm, U,  et al. 1995Mutation of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomasJ Clin Endocrinol Metab80308890CrossRefPubMedGoogle Scholar
  13. 13.
    Leboulleux, S, Travagli, JP, Caillou, B,  et al. 2002Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome. Influence on the stage on the clinical courseCancer944450PubMedGoogle Scholar
  14. 14.
    Machens, A, Gimm, O, Hinze, R,  et al. 2001Genotype–phenotype correlations in hereditary medullary thyroid carcinoma: Oncological features and biochemical propertiesJ Clin Endocrinol Metab8611049PubMedGoogle Scholar
  15. 15.
    Mulligan, LM, Eng, C, Healey, CS,  et al. 1994Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTCNat Genet6704CrossRefPubMedGoogle Scholar
  16. 16.
    Neumann, HPH, Hoegerle, S, Manz, T,  et al. 2002How many pathways to pheochromocytomaSem Nephrol228999Google Scholar
  17. 17.
    Mulligan, LM, Marsh, DJ, Robinson, BG,  et al. 1995Genotype–phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET mutation ConsortiumJ Intern Med2383436PubMedGoogle Scholar
  18. 18.
    Eng, C, Clayton, D, Schuffenecker, I,  et al. 1996The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET Mutation Consortium analysisJAMA27615759PubMedGoogle Scholar
  19. 19.
    Eng, C, Smith, DP, Mulligan, LM,  et al. 1994Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumoursHuman Mol Genet323741Google Scholar
  20. 20.
    Mulligan, LM, Kwok, JBJ, Healey, CS,  et al. 1993Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2ANature36345860CrossRefPubMedGoogle Scholar
  21. 21.
    Alvares Da Silva, AM, Maciel, RM, Dias Da Silva, MR,  et al. 2003A novel germ-line point mutation in RET exon 8 (gly(533)cys) in a large kindred with familial medullary thyroid carcinomaJ Clin Endocrinol Metab88543843PubMedGoogle Scholar
  22. 22.
    Decker, RA, Peacock, ML, Watson, P 1998Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype–phenotype correlationHuman Mol Genet712934Google Scholar
  23. 23.
    Kambouris, M, Jackson, CE, Feldman, GL 1996Diagnosis of multiple endocrine neoplasia [MEN] 2A, 2B and familial medullary thyroid cancer [FMTC] by multiplex PCR and heteroduplex analyses of RET proto-oncogene mutationsHum Mut86470PubMedGoogle Scholar
  24. 24.
    Blaugrund, JE, Johns, MM, Eby, YJ,  et al. 1994RET proto-oncogene mutations in inherited and sporadic medullary thyroid cancerHum Mol Genet318957PubMedGoogle Scholar
  25. 25.
    Frank-Raue, K, Höppner, W, Frilling, A,  et al. 1996Mutations of the ret protooncogene in German multiple endocrine neoplasia families: relation between genotype and phenotypeJ Clin Endocrinol Metab8117803PubMedGoogle Scholar
  26. 26.
    Klein, I, Erik, O, Homolya, V,  et al. 2001Molecular genetic diagnosis program of multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma syndrome in HungaryJ Endocrinol1706616PubMedGoogle Scholar
  27. 27.
    Igaz, P, Patocs, A, Racz, K,  et al. 2002Occurrence of pheochromocytoma in a MEN 2A family with codon 609 mutation of the RET proto-oncogeneJ Clin Endocrinol Metab872994Google Scholar
  28. 28.
    Donis-Keller, H, Dou, S, Chi, D,  et al. 1994Mutations in the RET proto-oncogene are associated with MEN 2A and FMTCHum Mol Genet323741PubMedGoogle Scholar
  29. 29.
    Landsvater, RM, Jansen, RP, Hofstra, RM,  et al. 1996Mutation analysis of the RET proto-oncogene in Duth families with MEN 2A, MEN 2B and FMTC: two novel mutations and one de novo mutation for MEN 2AHum Genet97114PubMedGoogle Scholar
  30. 30.
    Oriola, J, Paramo, C, Halperin, I,  et al. 1998Novel point mutation in exon 10 of the RET proto-oncogene in a family with medullary thyroid carcinomaAm J Med Genet782713PubMedGoogle Scholar
  31. 31.
    Nishikawa, M, Murakumo, Y, Imai, T,  et al. 2003Cys611Ser mutation in RET proto-oncogene in a kindred with medullary thyroid carcinoma and Hirschsprung diseaseEur J Hum Genet113648PubMedGoogle Scholar
  32. 32.
    Marsh, DJ, Robinson, BG, Andrew, S,  et al. 1994A rapid screening method for the detection of mutations in RET proto-oncogene in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma familiesGenomics234779PubMedGoogle Scholar
  33. 33.
    Pasini, B, Rossi, R, Ambrosio, MR,  et al. 2002RET mutation profile and variable clinical manifestations in a family with multiple endocrine neoplasia type 2A and Hirschsprung diseaseSurgery13137281Google Scholar
  34. 34.
    Attie, T, Pelet, A, Edery, P,  et al. 1995Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung diseaseHum Mol Genet413816PubMedGoogle Scholar
  35. 35.
    Eng, C, Mulligan, LM 1997Mutations of the RET proto-oncogene in the multiple endocrine neoplasia type 2 syndromes, related sporadic tumours, and Hirschsprung diseaseHum Mutat997109PubMedGoogle Scholar
  36. 36.
    Schuffenecker, I, Billaud, M, Calender, A,  et al. 1994RET proto–oncogene mutations in French MEN 2A and FMTC familiesHum Mol Genet3193943PubMedGoogle Scholar
  37. 37.
    Kitamura, Y, Goodfellow, PJ, Shimizu, K,  et al. 1997Novel germline RET proto-oncogene mutations associated with medullary thyroid carcinoma (MTC): mutation analysis in Japanese patients with MTCOncogene1431036PubMedGoogle Scholar
  38. 38.
    Verga, U, Fugazzola, L, Cambiaghi, S,  et al. 2003Frequent association between MEN 2A and cutaneous lichen amyloidosisClin Endocrinol5915661Google Scholar
  39. 39.
    McMahon, R, Mulligan, LM, Healey, CS,  et al. 1994Direct, non-radioactive detection of mutations in multiple endocrine neoplasia type 2A familiesHum Mol Genet36436PubMedGoogle Scholar
  40. 40.
    Seri, M, Celli, I, Betsos, N,  et al. 1997A cys 634gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosisClin Genet518690PubMedGoogle Scholar
  41. 41.
    Eng, C, Smith, DP, Mulligan, LM,  et al. 1995A novel point mutation in the tyrosine kinase domain of the RET proto-oncogene in sporadic medullary thyroid carcinoma and in a family with FMTCOncogene1050913PubMedGoogle Scholar
  42. 42.
    Antinolo, G, Marcos, I, Fernandez, RM,  et al. 2002A novel germline point mutation, c2304–>T, in codon 768 of the RET proto-oncogene in a patient with medullar thyroid carcinomaAm J Med Genet110857PubMedGoogle Scholar
  43. 43.
    Miyauchi, A, Matsuzuka, F, Hirai, K,  et al. 2002Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutationsWorld J Surg2610238PubMedGoogle Scholar
  44. 44.
    Mashek, W, Pichler, R, Rieger, R,  et al. 2002A new indentified germline mutation of the RET proto-oncogene responsible for familial medullary carcinoma in co-existence with a hyperfunctioning autonomous noduleClin Endocrinol56823Google Scholar
  45. 45.
    Berndt, I, Reuter, M, Saller, B,  et al. 1998A new hot spot for mutations in the ret proto-oncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2AJ Clin Endocrinol Metab837704PubMedGoogle Scholar
  46. 46.
    Gimm, O, Niederle, BE, Weber, T,  et al. 2002RET proto-oncogene mutations affecting codon 790/791: a mild form of multiple endocrine neoplasia type 2A syndromeSurgery1329529PubMedGoogle Scholar
  47. 47.
    Bolino, A, Schuffenecker, I, Luo, Y,  et al. 1995RET mutations in exons 13 and 14 of FMTC patientsOncogene1024159PubMedGoogle Scholar
  48. 48.
    Nilsson, O, Tisell, LE, Jansson, S,  et al. 1999Adrenal and extra-adrenal pheochromocytomas in a family with germline RET V804L mutationJAMA2811587PubMedGoogle Scholar
  49. 49.
    Fink, M, Wienhusel, A, Niederle, B, Haas, OA,  et al. 1996Distinction between sporadic and hereditary medullary thyroid carcinoma (MTC) by mutation analysis of the RET proto-oncogene. ‘Study Group Multiple Endocrine Neoplasia Austria (SMENA)’Int J Cancer693126PubMedGoogle Scholar
  50. 50.
    Demeester, R, Parma, J, Cochaux, P,  et al. 2001A rare variant, I852M, of the RET proto-oncogene in a patient with medullary thyroid carcinoma at age 20 yearsHum Mutat17354Google Scholar
  51. 51.
    Gimm, O, Marsh, DJ, Andrew, SD,  et al. 1997Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutationJ Clin Endocrinol Metab8239024CrossRefPubMedGoogle Scholar
  52. 52.
    Hofsra, RM, Fatturoso, O, Quadro, L,  et al. 1997A novel point mutation in the intracellular domain of the ret protoncogene in a family with medullary thyroid carcinomaJ Clin Endocrinol Metab8241768PubMedGoogle Scholar
  53. 53.
    Jimenez, C, Habra, MA, Huang, SC,  et al. 2004Pheochromocytoma and medullary thyroid carcinoma: a new genotype–phenotype correlation of the RET protooncogene 891 germline mutationJ Clin Endocrinol Metab8941425PubMedGoogle Scholar
  54. 54.
    Jimenez, C, Dang, GT, Schultz, PN,  et al. 2004A novel point mutation of the RET protooncogene involving the second intracellular tyrosine kinase domain in a family with medullary thyroid carcinomaJ Clin Endocrinol Metab8935216PubMedGoogle Scholar
  55. 55.
    Carlson, KM, Dou, S, Chi, D,  et al. 1994Single missense mutation in tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2BProc Natl Acad Sci USA91157983PubMedGoogle Scholar
  56. 56.
    Kitamura, Y, Scavarda, N, Wells, Jr SA,  et al. 1995Two maternally derived missense mutations in the tyrosine kinase domain of the RET protooncogene in a patient with de novo MEN 2BHum Mol Genet419878PubMedGoogle Scholar
  57. 57.
    Pigny, P, Bauters, C, Wemeau, JL,  et al. 1999A novel 9-base pair duplication in RET exon 8 in familial medullary thyroid carcinomaJ Clin Endocrinol Metab8417004PubMedGoogle Scholar
  58. 58.
    Hoppner, W, Ritter, MM 1997A duplication of 12 bp in the critical cysteine rich domain of the RET proto-oncogene results in a distinct phenotype of multiple endocrine neoplasia type 2AHumMol Genet658790Google Scholar
  59. 59.
    Hoppner W, Dralle H, Brabant G. Duplication of 9 base pairs in the critical cysteine rich domain of the RET proto-oncogene causes of multiple endocrine neoplasia type 2A. Hum Mutat 1998; (Suppl. 1): S128–S30Google Scholar
  60. 60.
    Tessitore, A, Sinisi, AA, Pasquali, MC,  et al. 1999A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogeneJ Clin Endocrinol Metab8435227CrossRefPubMedGoogle Scholar
  61. 61.
    Nunes, AB, Ezabella, MCL, Pereira, AC,  et al. 2002A novel Val648Ile substitution in RET protooncogene observed in a Cys634Arg multiple endocrine neoplasia type 2A kindred presenting with an adrenocorticotropin-producing pheochromocytomaJ Clin Endocrinol Metab87565861PubMedGoogle Scholar
  62. 62.
    Miyauchi, A, Futami, H, Hai, N,  et al. 1999Two Germline missense mutations at codon 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without 918 mutationJpn J Cancer Res9015PubMedGoogle Scholar
  63. 63.
    Kasprzak, L, Nolet, S, Gaboury, L,  et al. 2001Familial medullary thyroid carcinoma and prominent corneal nerves associated with the germline V804M and V778I mutations on the same allele of RETJ Med Genet387847CrossRefPubMedGoogle Scholar
  64. 64.
    Menko, FH, Luijt, RB, Valk, IAJ,  et al. 2002Atypical MEN type 2B associated with two germline RET mutations on the same allele not involving codon 918J Clin Endocrinol Metab873937CrossRefPubMedGoogle Scholar
  65. 65.
    Bartsch, DK, Hasse, C, Schug, C,  et al. 2000A RET double mutation in the germline of the kindred with FMTCExp Clin Endocrinol Diabetes10812832CrossRefPubMedGoogle Scholar
  66. 66.
    Maher, ER, Eng, C,  et al. 2003The pressure rises: update on genetics of phaeochromocytomaHuman Mol Genet11234754Google Scholar
  67. 67.
    Yip, L, Cote, GJ, Shapiro, SE,  et al. 2003Multiple endocrine neoplasia type 2. Evaluation of the genotype–phenotype relationshipArch Surg13840916PubMedGoogle Scholar
  68. 68.
    Punales, MK, Graf, H, Gross, JL, Maia, AL 2003RET codon 634 mutations in multiple endocrine neoplasia type 2A – variable clinical features and clinical outcomeJ Clin Endocrinol Metab8826449PubMedGoogle Scholar
  69. 69.
    Neumann, HPH, Eng, C, Mulligan, LM,  et al. 1995Consequences of direct genetic testing for germline mutations in the clinical management of families with multiple endocrine neoplasia, type IIJAMA274114951PubMedGoogle Scholar
  70. 70.
    Niccoli-Sire, P, Murat, A, Rohmer, V,  et al. 2001Familial medullary thyroid carcinoma with noncysteine RET mutations: phenotype-genotype relationship in a large series of patientsJ Clin Endocrinol Metab86374653PubMedGoogle Scholar
  71. 71.
    Karga, HJ, Karayianni, MK, Linos, DA,  et al. 1998Germ line mutation analysis in families with multiple endocrine neoplasia type 2A or familial medullary thyroid carcinomaEur J Endocrinol1394105PubMedGoogle Scholar
  72. 72.
    Marsh, DJ, Mulligan, LM, Eng, C 1997RET proto-oncogene mutations in multiple endocrine neoplasia type 2 and medullary thyroid carcinomaHorm Res4716878PubMedGoogle Scholar
  73. 73.
    Schuffenecker, I, Ginet, N, Goldgar, D,  et al. 1997Prevalence and parental origin of de novo RET mutations in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinomaAm J Hum Genet602337PubMedGoogle Scholar
  74. 74.
    Shannon, KE, Gimm, O, Hinze, R,  et al. 1999Germline V804M mutation in the RET proto-oncogene in two apparently sporadic cases of MTC presenting in the seventh decade of lifeJ Endocr Genet13945Google Scholar
  75. 75.
    Segouffin-Cariou, C, Billaud, M 2000Transforming ability of MEN2A-RET requires activation of the phosphatidylinositol 3-kinase/AKT signaling pathwayJ Biol Chem275356876PubMedGoogle Scholar
  76. 76.
    Lombardo, F, Baudin, E, Chiefari, E,  et al. 2002Familial medullary thyroid carcinoma: clinical variability and low aggressiveness associated with RET mutation at codon 804J Clin Endocrinol Metab87167480PubMedGoogle Scholar
  77. 77.
    Nilsson, O, Tisell, LE, Jansson, S,  et al. 1999Adrenal and extra-adrenal pheochromocytomas in a family with germline RET V804L mutationJAMA281158788PubMedGoogle Scholar
  78. 78.
    Machens, A, Niccoli-Sire, P, Hoegel, J,  et al. 2003Early malignant progression of hereditary medullary thyroid carcinomaN Engl J Med349151727PubMedGoogle Scholar
  79. 79.
    Cote, J, Gagel, RF 2003Lessons learned from management of a rare genetic cancerN Engl J Med349156668PubMedGoogle Scholar
  80. 80.
    Robledo, M, Gil, L, Pollan, M,  et al. 2003Polymorphism G691S/S904S of RET asgenetic modifiers of MEN 2ACancer Res63181419PubMedGoogle Scholar
  81. 81.
    Pomares, FJ, Rodriguez, JM, Nicolas, F,  et al. 2002Presurgical assessment of the tumor burden of familial medullary thyroid carcinoma by calcitonin testingJ Am Coll Surg1956304PubMedGoogle Scholar
  82. 82.
    Cohen, MS, Moley, JF 2003Surgical treatment of medullary thyroid carcinomaJ Int Med25361626Google Scholar
  83. 83.
    Viera, AEF, Mello, MP, Elias, LLK,  et al. 2002Molecular and biochemical screening for the diagnosis and management of medullary thyroid carcinoma in multiple endocrine neoplasia type 2AHorm Metab Res342026PubMedGoogle Scholar
  84. 84.
    Fleming, JB, Lee, JE, Bouvet, M,  et al. 1999Surgical strategy for treatment of medullary thyroid carcinomaAnn Surg230697707PubMedGoogle Scholar
  85. 85.
    Kebebew, E, Ituarte, PHG, Siperstein, AE,  et al. 2000Medullary thyroid carcinoma. Clinical characteristic, treatment, prognostic factors, and a comparison of staging systemsCancer88113948PubMedGoogle Scholar
  86. 86.
    Szinnai, G, Meier, C, Komminoth, P, Zumsteg, UW 2003Review of multiple endocrine neoplasia type 2A in children: therapeutic results of early thyroidectomy and prognostic value of codon analysisPediatrics1111329Google Scholar
  87. 87.
    Sanso, GE, Domene, HM, Garcia Rudaz, MC,  et al. 2002Very early detection of RET proto-oncogene mutation is crucial for preventive thyroidectomy in multiple endocrine neoplasia type 2 childrenCancer9432330PubMedGoogle Scholar
  88. 88.
    Gimm, O, Ukkat, J, Dralle, H 1998Determinative factors of biochemical cure after primary and reoperative surgery for sporadic medullary carcinomaWorld J Surg225628PubMedGoogle Scholar
  89. 89.
    Gonzales, JMR, Balsalobre, MD, Pomares, F,  et al. 2002Prophylactic thyroidectomy in MEN 2A syndrome: experience in a single centerJ Am Coll Surg19515966PubMedGoogle Scholar
  90. 90.
    de Kahraman, T, Groot, JWB, Rouwe, C 2002Acceptable age for prophylactic surgery in children with multiple endocrine neoplasia type 2aEJSO293315Google Scholar
  91. 91.
    Sherman S, Angelos P, Ball DWB et al. Medullary carcinoma in ‘Thyroid Carcinoma Practice Guidelines in Oncology’ version 1.2004. National Comprehensive Cancer Network 1–5Google Scholar
  92. 92.
    Simon, S, Pavel, M, Hensen, J,  et al. 2002Multiple endocrine neoplasia type 2A syndrome: surgical managementJ Pediatr Surg37897900PubMedGoogle Scholar
  93. 93.
    Dralle, H, Gimm, O, Simon, D,  et al. 1998Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experienceWorld J Surg2274451PubMedGoogle Scholar
  94. 94.
    Neumann, HPH, Bausch, B, McWhinney, SR,  et al. 2002Germ-line mutations in nonsyndromic pheochromocytomaN Engl J Med346145966CrossRefPubMedGoogle Scholar
  95. 95.
    Kaplan, NM 1998Pheochromocytoma (with a preface about incidental adrenal masses)Kaplan, NM eds. Clinical Hypertension.Williams and WilkinsBaltimore, MD34564Google Scholar
  96. 96.
    Modigliani, E, Vasen, HM, Raue, K,  et al. 1995Pheochromocytoma in multiple endocrine neoplasia type 2: European studyJ Intern Med.2383637PubMedGoogle Scholar
  97. 97.
    Neumann, HP 2002Imaging vs. biochemical testing for pheochromocytomaJAMA2883145PubMedGoogle Scholar
  98. 98.
    Sawka, AM, Jaeschke, R, Singh, RJ, Young, WF 2003A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholaminesJ Clin Endocrinol Metab885538PubMedGoogle Scholar
  99. 99.
    Eisenhofer, G 2003Editorial: Biochemical diagnosis of pheochromocytoma – is it time to switch to plasma-free metanephrinesJ Clin Endocrinol Metab885502PubMedGoogle Scholar
  100. 100.
    Eisenhofer, G, Lenders, JW, Linehan, WM,  et al. 1999Plasma normetanephrine and metanephrines for pheochromocytoma in von Hippel--Lindau disease and multiple endocrine neoplasia type 2N Engl J Med34018729PubMedGoogle Scholar
  101. 101.
    Raber, W, Raffesberg, W, Bischof, M,  et al. 2000Diagnostic efficacy of unconjugated plasma metanephrines for the detection of pheochromocytomaArch Intern Med160295763PubMedGoogle Scholar
  102. 102.
    Gardet, V, Gatta, B, Simonnet, G,  et al. 2001Lessons from an unpleasant surprise: a biochemical strategy for the diagnosis of pheochromocytomaJ Hypertens19102935PubMedGoogle Scholar
  103. 103.
    Goldstein, RE, O’Neill, JA, Holcomb, GW,  et al. 1999Clinical experience over 48 years with pheochromocytomaAnn Surg22975566PubMedGoogle Scholar
  104. 104.
    Pacak, K, Eisenhofer, G, Carasquillo, JA,  et al. 20016-[18F]Fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma.Hypertension3868PubMedGoogle Scholar
  105. 105.
    Hoegerle, S, Nitzsche, E, Altehoefer, C,  et al. 2003Pheochromocytomas: detection with 18F DOPA whole-body PET – initial resultsRadiology22250712Google Scholar
  106. 106.
    Lee, JE, Curley, SA, Gagel, RF,  et al. 1996Cortical-sparing adrenalectomy for patients with bilateral pheochromocytomaSurgery120106471PubMedGoogle Scholar
  107. 107.
    Neumann, HPH, Bender, BU, Reincke, M,  et al. 1999Adrenal-sparing surgery for phaeochromocytomaBr J Surg86947PubMedGoogle Scholar
  108. 108.
    Lamarre-Cliche, M, Gimenez-Roqueplo, AP, Billaud, E,  et al. 2002Effects of slow-release octerotide on urinary metanephrine excretion and plasma chromogranin A and catecholamine levels in patients with malignant or recurrent phaeochromocytomaClin Endocrinol5762934Google Scholar
  109. 109.
    Hartley, A, Spooner, D, Brunt, AM 2001Management of malignant pheochromocytoma: a retrospective review of the use of MIBG and chemotherapy in the West MidlandsClin Oncol133616Google Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Department of HypertensionNational Institute of CardiologyPoland

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