Multiple Endocrine Neoplasia Syndromes

  • Michael S. Racine
  • Beth A. Kurt
  • Pamela M. Thomas


The multiple endocrine neoplasia syndromes in children and adolescents present a challenging and varying group of familial tumor disorders, transmitted via autosomal dominant inheritance. Including MEN1, MEN2A and 2B, and familial medullary thyroid carcinoma, the MEN syndromes may affect children as young as 5 years, in MEN1, or as young as infants less than a year of age, as in MEN2-related medullary thyroid carcinoma (MTC). The MEN1 syndrome is composed primarily of pancreatic neuroendocrine tumors, parathyroid hyperplasia, and tumors of the anterior pituitary gland. The natural history of MEN1 in 160 children and adolescents under the age of 21 years has been elucidated in a large French series by the Groupe ďétude des Tumeurs Endocrines, shedding light on the varied combinations of presentations in young patients. The MEN2 syndromes are composed of MTC, pheochromocytoma, and more variably parathyroid hyperplasia, with a characteristic feature of MEN2B being mucosal neuromas. MEN2 is rarer than MEN1 and presents unique challenges in management, including the appropriate age for thyroidectomy and the evaluation and management of pheochromocytoma. DNA analysis has revolutionized the clinical management of MEN1 and MEN2. We discuss the diagnosis, management, and recommended screening strategies for this group of tumor syndromes, relative to the pediatric age group.


Acromegaly Cushing’s disease Genetic Gastrinoma Hyperparathyroidism Hypoglycemia Insulinoma Medullary thyroid cancer Neoplasia Neuroendocrine Pancreatic neuroendocrine tumor Pheochromocytoma Pituitary adenoma Prolactinoma Tumor 


  1. 1.
    Pellegata NS, Quintanilla-Martinez L, Siggelkow H, et al. Germ-line mutations in p27 Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006;103:15558–63.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954;16:363–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Steiner AL, Goodman AD, Powers SR. Study of kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and Cushing’s disease: multiple endocrine neoplasia, type 2. Medicine (Baltimore). 1968;47:371–409.CrossRefGoogle Scholar
  4. 4.
    Waterlot C, Porchett N, Bauters C, et al. Type 1 multiple endocrine neoplasia (MEN1): contribution of genetic analysis to the screening and follow-up of a large French kindred. Clin Endocrinol (Oxf). 1999;51:101–7.CrossRefGoogle Scholar
  5. 5.
    Brandi ML, Gagel RF, Angeli A, et al. Consensus guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86:5658–71.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Thakker RV. Multiple endocrine neoplasia type 1 (MEN1). In: Robertson RP, Thakker RV, editors. Translational endocrinology and metabolism, vol. 2. Chevy Chase: The Endocrine Society; 2011. p. 13–44.Google Scholar
  7. 7.
    Trump D, Farren B, Wooding C, et al. Clinical studies of multiple endocrine neoplasia type 1 (MEN1). Q J Med. 1996;89:653–69.CrossRefGoogle Scholar
  8. 8.
    Veldhuis JD, Norton JA, Wells SA Jr, et al. Therapeutic controversy: surgical versus medical management of multiple endocrine neoplasia (MEN) type 1. J Clin Endocrinol Metab. 1997;82:357–64.PubMedCrossRefGoogle Scholar
  9. 9.
    Hoff AO, Gagel RF. Multiple endocrine neoplasia types 1 and 2: phenotype, genotype, diagnosis, and therapeutic plan with special reference to children and adolescents. Curr Opin Endocrinol Diabetes Obes. 1997;4:91–9.CrossRefGoogle Scholar
  10. 10.
    Asgharian B, Chen YJ, Patronas NJ, et al. Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin Cancer Res. 2004;10:869–80.PubMedCrossRefGoogle Scholar
  11. 11.
    Goudet P, Dalac A, Le Bras M, et al. MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d’étude des Tumeurs endocrines. J Clin Endocrinol Metab. 2015;100:1568–77.PubMedCrossRefGoogle Scholar
  12. 12.
    Flanagan DE, Armitage M, Clein GP, Thakker RV. Prolactinoma presenting in identical twins with multiple endocrine neoplasia type 1. Clin Endocrinol. 1996;45:117–20.CrossRefGoogle Scholar
  13. 13.
    Benson L, Ljunghall S, Åkerström G, et al. Hyperparathyroidism presenting as the first lesion in multiple endocrine neoplasia type 1. Am J Med. 1987;82:731–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Marx S, Spiegel AM, Skarulis MC, et al. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1988;129:484–94.CrossRefGoogle Scholar
  15. 15.
    Chanson P, Cadiot G, Murat A. Management of patients and subjects at risk for multiple endocrine neoplasia type 1. Horm Res. 1997;47:211–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Falchetti A, Marini F, Luzi E, et al. Multiple endocrine neoplasia type 1 (MEN1): not only inherited endocrine tumors. Genet Med. 2009;11:825–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Skogseid B, Eriksson B, Lundqvist G, et al. Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. J Clin Endocrinol Metab. 1991;73:281–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Ballard HS, Frame B, Hartsock RJ. Familial multiple endocrine adenoma-peptic ulcer complex. Medicine. 1964;43:481–516.PubMedCrossRefGoogle Scholar
  19. 19.
    Eberle F, Grum R. Multiple endocrine neoplasia type 1 (MEN-I). Ergberg Inn Med Kinderheilkd. 1981;46:76–149.Google Scholar
  20. 20.
    Eller-Vainicher C, Chiodini I, Battista C, et al. Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity. J Bone Miner Res. 2009;24:1404–10.PubMedCrossRefGoogle Scholar
  21. 21.
    Lourenҫo DM Jr, Coutinho FL, Toledo RA, et al. Early-onset, progressive, frequent, extensive, and severe bone mineral and renal complications in multiple endocrine neoplasia type 1-associated primary hyperparathyroidism. J Bone Miner Res. 2010;25:2382–491.CrossRefGoogle Scholar
  22. 22.
    Lourenҫo DM Jr, Coutinho FL, Toledo RA, et al. Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1. Clinics (Sao Paulo). 2012;67(suppl 1):99–108.Google Scholar
  23. 23.
    Eastell R, Brandi ML, Costa AG, D'Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the fourth international workshop. J Clin Endocrinol Metab. 2014;99:3570–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Eslamy HK, Ziessman HA. Parathyroid scintigraphy in patients with primary hyperparathyroidism: 99mTc sestamibi SPECT and SPECT/CT. Radiographics. 2008;28:1461–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151:959–68.PubMedCrossRefGoogle Scholar
  26. 26.
    Malmaeus J, Benson L, Johansson H, et al. Parathyroid surgery in the multiple endocrine neoplasia type 1 syndrome: choice of surgical procedure. World J Surg. 1986;10:668–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Thompson NW. The techniques of initial parathyroid explorative and reoperative parathyroidectomy. In: Thompson NW, Vinik AI, editors. Endocrine surgery update. New York: Grune & Stratton; 1983. p. 365–83.Google Scholar
  28. 28.
    Lambert LA, Shapiro SE, Lee JE, et al. Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Arch Surg. 2005;140:374–82.PubMedCrossRefGoogle Scholar
  29. 29.
    Rizzoli R, Green J III, Marx SJ. Primary hyperparathyroidism in familial multiple endocrine neoplasia type 1: long term follow-up of serum calcium levels after parathyroidectomy. Am J Med. 1985;78:467–74.PubMedCrossRefGoogle Scholar
  30. 30.
    Newey PJ, Jeyabalan J, Walls GV, et al. Asymptomatic children with multiple endocrine neoplasia type 1 mutations may harbor nonfunctioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 2009;94:3640–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Lévy-Bohbot N, Merle C, Goudet P, et al; for the Groupe des Tumeurs Endocrines. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs endocrines) registry. Gastroenterol Clin Biol. 2004;28:1075–1081.Google Scholar
  32. 32.
    Cemeroglu AP, Racine MS, Kleis L, et al. Metastatic insulinoma in a 16 year-old adolescent male with MEN1: a case report and review of the literature. AACE Clinical Case Rep. 2016;2(3):e247–50.CrossRefGoogle Scholar
  33. 33.
    Thompson NW. The surgical management of hyperparathyroidism and endocrine disease of the pancreas in the multiple endocrine neoplasia type 1 patient. J Intern Med. 1995;238:269–80.PubMedCrossRefGoogle Scholar
  34. 34.
    Gagel RF. Multiple endocrine neoplasia. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders; 2008. p. 1709–10.Google Scholar
  35. 35.
    Roy PK, Venzon DJ, Shojamanesh H, et al. Zollinger-Ellison syndrome. Medicine. 2000;79:46–9.CrossRefGoogle Scholar
  36. 36.
    Jensen RT. Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J Intern Med. 1998;243:477–88.PubMedCrossRefGoogle Scholar
  37. 37.
    Cryer PE. Glucose homeostasis and hypoglycemia. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders; 2008. p. 1522.Google Scholar
  38. 38.
    Berna MJ, Annibale B, Marignani M, et al. A prospective study of gastric carcinoids and enterochromaffin-like cell changes in multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: identification of risk factors. J Clin Endocrinol Metab. 2008;93:1582–91.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Skogseid B, Öberg K, Benson L, et al. A standardized meal stimulation test of the endocrine pancreas for early detection of pancreatic endocrine tumors in MEN type 1 syndrome: five years experience. J Clin Endocrinol Metab. 1987;64:1233–40.PubMedCrossRefGoogle Scholar
  40. 40.
    de Laat JM, Pieterman CR, Weijmans M, et al. Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients. J Clin Endocrinol Metab. 2013;98:4143–51.PubMedCrossRefGoogle Scholar
  41. 41.
    Bartsch DK, Albers M, Knoop R, et al. Enucleation and limited pancreatic resection provide long-term cure for insulinoma in multiple endocrine neoplasia type 1. Neuroendocrinology. 2013;98:290–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Rossi RE, Massironi S, Conte D, et al. Therapy for metastatic pancreatic neuroendocrine tumors. Ann Transl Med. 2014;2:8.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Pavel M, Baudin E. Couvelard a, et al; ENETS consensus guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2012;95:157–76.PubMedCrossRefGoogle Scholar
  44. 44.
    Lewis RB, Lattin GE Jr, Paal E. Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics. 2010;30:1445–64.PubMedCrossRefGoogle Scholar
  45. 45.
    Lamberts SW, Bakker WH, Reubi JC, et al. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med. 1990;323:1246–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Sadowski SM, Neychev V, Millo C, et al. Prospective study of 68Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. J Clin Oncol. 2016;34:588–96.PubMedCrossRefGoogle Scholar
  47. 47.
    Skogseid B, Grama D, Rastad J, et al. Operative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1. J Intern Med. 1995;238:281–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Vergès B, Boureille F, Goudet P, et al. Pituitary disease in MEN type 1: data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87:457–65.PubMedCrossRefGoogle Scholar
  49. 49.
    Stratakis CA, Schussheim DH, Freedman SM, et al. Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2000;85:4776–80.PubMedGoogle Scholar
  50. 50.
    Goudet P, Bonithon-Kopp C, Murat A, et al. Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d’etude des Tumeurs endocrines. Eur J Endocrinol. 2011;165:97–105.PubMedCrossRefGoogle Scholar
  51. 51.
    Colao A, Loche S, Cappabianca P, et al. Pituitary adenomas in children and adolescents. Clinical presentation, diagnosis, and therapeutic strategies. Endocrinologist. 2000;10:314–27.CrossRefGoogle Scholar
  52. 52.
    Mindermann T, Wilson CB. Pediatric pituitary adenomas. Neurosurgery. 1995;36:259–69.PubMedCrossRefGoogle Scholar
  53. 53.
    Lafferty AR, Chrousos GP. Pituitary tumors in children and adolescents. J Clin Endocrinol Metab. 1999;84:4317–23.PubMedCrossRefGoogle Scholar
  54. 54.
    Melmed S, Kleinberg D. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders; 2008. p. 217.Google Scholar
  55. 55.
    Nieman LK. Establishing the diagnosis of Cushing’s syndrome. 2015. Retrieved from Accessed 24 July 2016.
  56. 56.
    Colao A, Loche S, Cappa M, et al. Prolactinomas in children and adolescents. Clinical presentation and long-term follow-up. J Clin Endocrinol Metab. 1998;83:2777–80.PubMedCrossRefGoogle Scholar
  57. 57.
    Gan HW, Bulwer C, Jeelani O, et al. Treatment-resistant pediatric giant prolactinoma and multiple endocrine neoplasia type 1. J Pediatr Endocrinol. 2015;2015(1):15. Epub 2015 Jul 15.CrossRefGoogle Scholar
  58. 58.
    Fideleff HL, Boquete HR, Suárez MG, et al. Prolactinoma in children and adolescents. Horm Res. 2009;72:197–205.PubMedCrossRefGoogle Scholar
  59. 59.
    Chandrasekharappa SC, Guru SC, Manickam P, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276:404–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Agarwal SK, Guru SC, Heppner C, et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell. 1999;96:143–52.PubMedCrossRefGoogle Scholar
  61. 61.
    Huang SC, Zhuang Z, Weil RJ, et al. Nuclear/cytoplasmic localisation of the multiple endocrine neoplasia type 1 gene product, menin. Lab Investig. 1999;79:301–10.PubMedGoogle Scholar
  62. 62.
    Farid NR, Buehler S, Russell NA, et al. Prolactinomas in familial multiple endocrine neoplasia syndrome type I. Relationship to HLA and carcinoid tumors. Am J Med. 1980;69:874–80.PubMedCrossRefGoogle Scholar
  63. 63.
    Johnston LB, Chew SL, Trainer PJ, et al. Screening children at risk of developing inherited endocrine neoplasia syndromes. Clin Endocrinol (Oxf). 2000;52:127–36.CrossRefGoogle Scholar
  64. 64.
    Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97:5658–71.CrossRefGoogle Scholar
  65. 65.
    Sugg SL, Sipple JH. In: Pasieka JL, Lee JA, editors. Surgical Endocrinopathies – clinical management and the founding figures. Cham, Switzerland: Springer International Publishing; 2015. p. 397–9.Google Scholar
  66. 66.
    Sipple JH. The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med. 1961;31:163–6.CrossRefGoogle Scholar
  67. 67.
    Tashjian AH Jr, Howland BG, Melin KEW, et al. Immunoassay of human calcitonin: clinical measurement, relation to serum calcium and studies in patients with medullary carcinoma. N Engl J Med. 1970;283:90–5.Google Scholar
  68. 68.
    Mulligan LM, Kwok JBJ, Healey CS, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363:458–61.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Donis-Keller H, Dou S, Chi D, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993;2:851–6.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    de Groot JW, Links TP, Plukker JT, et al. RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors. Endocr Rev. 2006;27:535–60.PubMedCrossRefGoogle Scholar
  71. 71.
    Wells SA Jr, Asa SL, Dralle H, et al. American Thyroid Association guidelines task force on medullary thyroid carcinoma, revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25:567.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Saad MF, Ordonez NG, Rashid RK, et al. Medullary carcinoma of the thyroid: a study of the clinical features and prognostic factors in 161 patients. Medicine. 1984;63:319–442.PubMedCrossRefGoogle Scholar
  73. 73.
    Nunziata V, Giannattosio R, di Giovanni G, et al. Hereditary localized pruritus in affected members of a kindred with multiple endocrine neoplasia type 2A (Sipple’s syndrome). Clin Endocrinol. 1989;30:57–63.CrossRefGoogle Scholar
  74. 74.
    Gagel RF, Levy ML, Donovan DT, et al. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Inter Med. 1989;111:802–6.CrossRefGoogle Scholar
  75. 75.
    Marquard J, Eng C. Multiple endocrine neoplasia type 2. GeneReviews [Internet] 2015. Retrieved from Accessed 29 July 2016.
  76. 76.
    Frank-Raue K, Rybicki LA, Erlic Z, et al. Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10. Hum Mutat. 2011;32:51–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Farndon JR, Leight GS, Dilley WG, et al. Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity. Br J Surg. 1986;73:2278–81.CrossRefGoogle Scholar
  78. 78.
    Williams ED, Pollock DJ. Multiple mucosa neuromata with endocrine tumours. A syndrome allied to von Recklinghausen’s disease. J Pathol Bacteriol. 1966;91:71–80.PubMedCrossRefGoogle Scholar
  79. 79.
    Jacobs JM, Hawes MJ. From eyelid bumps to thyroid lumps: report of a MEN type IIb family and review of the literature. Ophthal Plast Reconstr Surg. 2001;17:195–201.PubMedCrossRefGoogle Scholar
  80. 80.
    Eng C. RET proto-oncogene in the development of human cancer. J Clin Oncol. 1999;17:380–93.PubMedCrossRefGoogle Scholar
  81. 81.
    Schӓppi MG, Staiano A, Milla PJ, et al. A practical guide for the diagnosis of primary enteric nervous system disorders. J Pediatr Gastroenterol Nutr. 2013;57:677–86.CrossRefGoogle Scholar
  82. 82.
    Qualia CM, Brown MR, Ryan CK, et al. Oral mucosal neuromas leading to the diagnosis of multiple endocrine neoplasia type 2B in a child with intestinal pseudo-obstruction. Gastroenterol Hepatol (NY). 2007;3:208–11.Google Scholar
  83. 83.
    Padberg BC, Holl K, Schroder S. Pathology of multiple endocrine neoplasia 2A and 2B: a review. Horm Res. 1992;38(suppl2):24–30.PubMedCrossRefGoogle Scholar
  84. 84.
    Skinner MA, Moley JA, Dilley WG, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353:1105–13.PubMedCrossRefGoogle Scholar
  85. 85.
    Wolfe HJ, Melvin KE, Cervi-Skinner SJ, et al. C-cell hyperplasia preceding medullary thyroid carcinoma. N Engl J Med. 1973;289:437–41.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Gagel RF, Tashjian AH Jr, Cummings T, et al. The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a: an 18-year experience. N Engl J Med. 1988;318:478–84.PubMedCrossRefGoogle Scholar
  87. 87.
    Shankar RK, Rutter MJ, Chernausek SD, et al. Medullary thyroid cancer in a 9-week-old infant with familial MEN 2B: implications for timing of prophylactic thyroidectomy. Int J Pediatr Endocrinol. 2012;2012:25.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Gagel RF, Jackson CE, Block MA, et al. Age-related probability of development of hereditary medullary thyroid carcinoma. J Pediatr. 1982;101:941–6.PubMedCrossRefGoogle Scholar
  89. 89.
    Telander RL, Zimmerman D, van Heerden JA, Sizemore GW. Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2. J Pediatr Surg. 1986;21:1190–4.PubMedCrossRefGoogle Scholar
  90. 90.
    Graham SM, Genel M, Touloukian RJ, et al. Provocative testing for occult medullary carcinoma of the thyroid: findings in seven children with MEN type IIa. J Pediatr Surg. 1987;22:501–3.PubMedCrossRefGoogle Scholar
  91. 91.
    Norton JA, Froome LC, Farrell RE, et al. MEN 2b. The most aggressive form of medullary thyroid carcinoma. Surg Clin North Am. 1979;59:109–18.PubMedCrossRefGoogle Scholar
  92. 92.
    Thosani S, Ayala-Ramirez M, Palmer L, et al. The characterization of pheochromocytoma and its impact on overall survival in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab. 2013;98:E1813–9.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Machens A, Lorenz K, Dralle H. Peak incidence of pheochromocytoma and primary hyperparathyroidism in multiple endocrine neoplasia 2: need for age-adjusted biochemical screening. J Clin Endocrinol Metab. 2013;98:E336–45.PubMedCrossRefGoogle Scholar
  94. 94.
    Rowland KJ, Chernock RD, Moley JF. Pheochromocytoma in an 8-year-old patient with multiple endocrine neoplasia type 2A: implications for screening. J Surg Oncol. 2013;108:203–6.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Jadoul M, Leo JR, Berends MJ, et al. Pheochromocytoma-induced hypertensive encephalopathy revealing MEN 2A syndrome in a 13-year old boy: implications for screening procedures and surgery. Horm Metab Res Suppl. 1989;21:46–9.PubMedGoogle Scholar
  96. 96.
    Scott HW, Halter SA. Oncologic aspects of pheochromocytoma: the importance of follow-up. Surgery. 1984;96:1061–6.PubMedGoogle Scholar
  97. 97.
    Stenstrom G, Ernest I, Tisell LE. Long-term results in 64 patients operated upon for pheochromocytoma. Acta Med Scand. 1988;223:345–52.PubMedCrossRefGoogle Scholar
  98. 98.
    Pomares FJ, Cañas R, Rodriguez JM, et al. Differences between sporadic and multiple endocrine neoplasia type 2A phaeochromocytoma. Clin Endocrinol. 1998;48:195–200.CrossRefGoogle Scholar
  99. 99.
    Caty MG, Coran AG, Geagen M, Thompson NW. Current diagnosis and treatment of pheochromocytoma in children. Experience with 22 consecutive tumors in 14 patients. Arch Surg. 1990;125:978–81.PubMedCrossRefGoogle Scholar
  100. 100.
    Gagel RF, Marx SJ. Multiple endocrine neoplasia. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders; 2008. p. 1721–4.Google Scholar
  101. 101.
    Mathew CG, Chin KS, Easton DF, et al. A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10. Nature. 1987;328:527–8.PubMedCrossRefGoogle Scholar
  102. 102.
    Simpson NE, Kidd KK, Goodfellow PJ, et al. Assignment of multiple endocrine neoplasia type 2A on chromosome 10 by linkage. Nature. 1987;328:528–30.PubMedCrossRefGoogle Scholar
  103. 103.
    Ponder BAJ. The phenotypes associated with RET mutations in the multiple endocrine neoplasia type 2 syndrome. Cancer Res Suppl. 1999;59:1736s–42s.Google Scholar
  104. 104.
    Evans DR, Fleming JB, Lee JE, et al. The surgical treatment of medullary thyroid carcinoma. Sem. Surg Oncol. 1999;16:50–63.CrossRefGoogle Scholar
  105. 105.
    Yip L, Cote GJ, Shapiro SE, et al. Multiple endocrine neoplasia type 2: evaluation of the genotype-phenotype relationship. Arch Surg. 2003;138:409–16.PubMedCrossRefGoogle Scholar
  106. 106.
    Stratakis CA, Ball DW. A concise genetic and clinical guide to multiple endocrine neoplasia and related syndromes. J Pediatr Endocrinol Metab. 2000;13:457–65.PubMedGoogle Scholar
  107. 107.
    Gagel RF. Multiple endocrine neoplasia type 2 – impact of genetic screening on management. In: Arnold A, editor. Endocrine neoplasms. Norwell, MA: Kluwer Academic Publishers; 1997. p. 421–41.CrossRefGoogle Scholar
  108. 108.
    Bravo EL. Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma. Endocr Rev. 1994;15:356–68.PubMedCrossRefGoogle Scholar
  109. 109.
    Young WF. Pheochromocytoma in children. 2015. Retrieved from Accessed 7 Aug 2016.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Michael S. Racine
    • 1
  • Beth A. Kurt
    • 2
  • Pamela M. Thomas
    • 3
  1. 1.Eugene EndocrinologyEugeneUSA
  2. 2.Pediatric Hematology and OncologySpectrum Health Helen DeVos Children’s HospitalGrand RapidsUSA
  3. 3.FayettevilleUSA

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