Pediatric Multiple Endocrine Neoplasia Treatment & Management

  • Author: Alicia Diaz-Thomas, MD, MPH; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Apr 19, 2012
 

Approach Considerations

Treatments for the various conditions associated with multiple endocrine neoplasia (MEN) include the following:

  • Hypercalcemia - For patients with type 1 MEN who have hypercalcemia, surgery is the treatment of choice, including removal of 3.5 parathyroid glands
  • Gastrinoma - The current treatment consists of PPIs to reduce acid hypersecretion
  • Insulinoma - Surgery is the therapy of choice; unresectable tumors are treated with diazoxide
  • Glucagonoma - Glucagonomas are surgically removed
  • VIPoma - Octreotide controls symptoms (diarrhea) in 80% of patients; however, surgical tumor removal should be attempted
  • Prolactinoma - Prolactinomas are treated with dopamine agonists, such as bromocriptine or cabergoline
  • GH-producing pituitary tumor - These tumors are treated by transsphenoidal surgery; in rare instances, medical therapy with a GH receptor antagonist is recommended

Chemotherapy with streptozocin and dacarbazine may reduce the size of nonoperable neuroendocrine tumors.

Next

Surgery for Type 1 MEN

Type 1 MEN with hyperparathyroidism

In patients with type 1 MEN who have hyperparathyroidism, surgery is the treatment of choice if any of the following conditions are present:

  • Serum albumin–adjusted serum calcium level that is more than 1 mg/dL of the upper limit of the reference range
  • Kidney stones
  • PTH-induced bone disease with a T score of -2.5
  • 24-Hour urinary calcium excretion of more than 400mg

Type 1 MEN with ZES

In patients with type 1 MEN with ZES who have hypercalcemia, perform parathyroidectomy before abdominal tumor resection. In these patients, parathyroid surgery is indicated even in mild forms of hypercalcemia because serum calcium levels in the reference range are often associated with lower serum gastrin levels and consecutively lower gastric acid secretion (high calcium stimulates gastrin in these patients).

Removal of 3.5-4 parathyroid glands controls hypercalcemia. If 4 glands are removed, immediate autograft of parathyroid tissue into the musculature of the nondominant arm is indicated.

Some authors recommend taking careful operative notes and marking the residual parathyroid tissue with clips, because reoperation in patients with type 1 MEN is likely.

Gastrinoma

The role of surgery in ZES and type 1 MEN remains controversial because cure is only occasionally achieved. Most tumors are multicentric, raising the possibility of recurrence. Surgery may be indicated in patients with positive findings on imaging studies and no distant metastases. Gastrinomas are found in the duodenal wall, in the pancreas, or in lymph nodes.

Local tumor excision is preferred, with larger tumors of the pancreatic body or tail removed by distal pancreatectomy. This approach may reduce the risk of subsequent metastatic disease to the liver.

Resection of liver metastases may be beneficial. Total pancreatectomy is not indicated, because of the deleterious effects of this procedure (eg, pancreatic exocrine insufficiency, diabetes mellitus).

Insulinoma

Insulinomas are large, single tumors that can be enucleated. Resection may result in cure, although insulinomas in type 1 MEN may be multicentric.

Some authors recommend subtotal pancreatectomy (≥80% of the pancreas) in patients with multiple tumors or when the tumor is not localized. Surgical debulking in metastatic disease may reduce hypoglycemia to a certain extent.

Intraoperative ultrasonography facilitates tumor identification. Other methods include intraoperative monitoring of plasma glucose and insulin levels.

VIPoma

In VIPoma, resection of single and multiple tumors is indicated, which may include a pancreatic tail resection.

Carcinoid tumors

Carcinoid tumors are removed surgically; half of the tumors, particularly thymic carcinoids, are locally invasive or metastatic.[36]

Pituitary tumors

Transsphenoidal pituitary surgery is aimed at resection of any pituitary mass, particularly in acromegaly. Patients with incomplete resection remain on treatment with dopamine agonists.

Prolactinoma

Prolactinomas may be large and multicentric. The recurrence rate after surgical removal is high, and medical treatment is now the therapy of choice. Transsphenoidal surgery with external radiation therapy (external beam or gamma knife) is indicated in patients in whom long-term bromocriptine therapy is ineffective.

Previous
Next

Surgery or Type 2 MEN

Total thyroidectomy with radical lymph-node dissection is recommended in patients aged 5 years if a RET germline mutation is identified. All regional lymph nodes must be removed, even if they are not macroscopically suspected. Before any surgery, screening for pheochromocytomas must be performed. For patients with germline mutations in codons 790/791, the age at which total thyroidectomy should be performed is controversial.

Pheochromocytomas require surgical excision under alpha-adrenergic blockade, starting 7-10 days before surgery (target blood pressure is 120/80 mm Hg while seated and a systolic blood pressure of >90 mm Hg while standing/upright).

Pheochromocytomas in patients with type 2 MEN may be bilateral. Explore both adrenal glands during surgery.

Patients with a pheochromocytoma and MTC should receive appropriate preparation with alpha-blocker therapy. Then, the pheochromocytoma should be removed first to avoid life-threatening complications (eg, hypertensive crisis, arrhythmias) caused by the adrenal tumor. Laparoscopic adrenalectomy has now become a routine procedure.

Previous
Next

Inpatient Care

After parathyroid surgery, monitor serum ionized calcium and magnesium levels. Transient hypoparathyroidism frequently develops and requires calcium and vitamin D supplementation. In rare cases, hungry-bone syndrome may ensue, with rapid declines in serum calcium and magnesium levels.

Somatostatin therapy is indicated particularly in patients with acromegaly in whom surgery did not achieve complete tumor removal. Tumor shrinkage can be expected in one third of patients, and normalization of IGF-1 levels can be expected in as many as two thirds.

Pregnancy may ensue with treatment that includes cabergoline or bromocriptine in patients with prolactinoma.

Previous
Next

Outpatient Care

In MTC, measure serum calcitonin levels every 6-12 months after surgery. Elevated serum levels in the neck region indicate recurrence that possibly requires further surgery. However, micrometastases often cannot be visualized by using current imaging techniques.

The resection of one endocrine tumor does not exclude a second tumor, even after an interval of several years. Patients need lifelong surveillance, as do their offspring.

Pheochromocytomas are monitored with blood pressure and plasma free metanephrines as well as 24-hour urinary catecholamines, including fractionated metanephrine measurements, to exclude recurrence.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Alicia Diaz-Thomas, MD, MPH  Assistant Professor of Pediatrics, University of Tennessee Health Science Center, Memphis

Alicia Diaz-Thomas, MD, MPH is a member of the following medical societies: American Academy of Clinical Endocrinology, Endocrine Society, and Tennessee Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

George P Chrousos, MD, FAAP, MACP, MACE, FRCP (London) Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Robert J Ferry Jr, MD, Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Nothing to disclose.

Christian A Koch, MD, PhD, FACP, FACE Professor and Director, Division of Endocrinology, University of Mississippi Medical Center

Christian A Koch, MD, PhD, FACP, FACE is a member of the following medical societies: American Academy of Neurology, American Association of Clinical Endocrinologists, American College of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Society for Clinical Pharmacology and Therapeutics, American Society for Dermatologic Surgery, Endocrine Society, and German Diabetes Society

Disclosure: NovoNordisk Honoraria Consulting

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI

Klaus Radebold, MD, PhD Research Associate, Department of Surgery, Yale University School of Medicine

Klaus Radebold, MD, PhD is a member of the following medical societies: American Gastroenterological Association and New York Academy of Sciences

Disclosure: Nothing to disclose.

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References

  1. Wermer P. Endocrine adenomatosis and peptic ulcer in a large kindred. Inherited multiple tumors and mosaic pleiotropism in man. Am J Med. Aug 1963;35:205-12. [Medline].

  2. Eng C. RET proto-oncogene in the development of human cancer. J Clin Oncol. Jan 1999;17(1):380-93. [Medline].

  3. Doherty GM, Olson JA, Frisella MM, Lairmore TC, Wells SA Jr, Norton JA. Lethality of multiple endocrine neoplasia type I. World J Surg. Jun 1998;22(6):581-6; discussion 586-7. [Medline].

  4. Decker RA, Peacock ML. Occurrence of MEN 2a in familial Hirschsprung's disease: a new indication for genetic testing of the RET proto-oncogene. J Pediatr Surg. Feb 1998;33(2):207-14. [Medline].

  5. Agarwal SK, Kennedy PA, Scacheri PC, Novotny EA, Hickman AB, Cerrato A, et al. Menin molecular interactions: insights into normal functions and tumorigenesis. Horm Metab Res. Jun 2005;37(6):369-74. [Medline].

  6. Agarwal SK, Lee Burns A, Sukhodolets KE, Kennedy PA, Obungu VH, Hickman AB, et al. Molecular pathology of the MEN1 gene. Ann N Y Acad Sci. Apr 2004;1014:189-98. [Medline].

  7. Anlauf M, Schlenger R, Perren A, Bauersfeld J, Koch CA, Dralle H, et al. Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol. May 2006;30(5):560-74. [Medline].

  8. Bahlo M, Schott M, Kaminsky E, Cupisti K. [Multiple endocrine neoplasia 2a: late manifestation of a newly-discovered mutation]. Dtsch Med Wochenschr. Mar 2008;133(10):464-6. [Medline].

  9. Berna MJ, Annibale B, Marignani M, Luong TV, Corleto V, Pace A, 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. May 2008;93(5):1582-91. [Medline].

  10. Brauer VF, Scholz GH, Neumann S, Lohmann T, Paschke R, Koch CA. RET germline mutation in codon 791 in a family representing 3 generations from age 5 to age 70 years: should thyroidectomy be performed?. Endocr Pract. Jan-Feb 2004;10(1):5-9. [Medline].

  11. Byard RW, Thorner PS, Chan HS, Griffiths AM, Cutz E. Pathological features of multiple endocrine neoplasia type IIb in childhood. Pediatr Pathol. 1990;10(4):581-92. [Medline].

  12. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). Jul 1985;64(4):270-83. [Medline].

  13. Ciccarelli A, Daly AF, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8(1):3-6. [Medline].

  14. Cohen MS, Phay JE, Albinson C, DeBenedetti MK, Skinner MA, Lairmore TC, et al. Gastrointestinal manifestations of multiple endocrine neoplasia type 2. Ann Surg. May 2002;235(5):648-54; discussion 654-5. [Medline].

  15. Craven DE, Goodman D, Carter JH. Familial multiple endocrine adenomatosis. Multiple endocrine neoplasia, type I. Arch Intern Med. Apr 1972;129(4):567-9. [Medline].

  16. Eriksson B, Bergstrom M, Orlefors H, Sundin A, Oberg K, Langstrom B. Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies. Q J Nucl Med. Mar 2000;44(1):68-76. [Medline].

  17. Eriksson B, Oberg K, Stridsberg M. Tumor markers in neuroendocrine tumors. Digestion. 2000;62 Suppl 1:33-8. [Medline].

  18. Ferry RJ Jr, Kelly A, Grimberg A, Koo-McCoy S, Shapiro MJ, Fellows KE, et al. Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism. J Pediatr. Aug 2000;137(2):239-46. [Medline].

  19. Frank K, Raue F, Gottswinter J, Heinrich U, Meybier H, Ziegler R. Importance of early diagnosis and follow-up in multiple endocrine neoplasia (MEN II B). Eur J Pediatr. Dec 1984;143(2):112-6. [Medline].

  20. Frohnauer MK, Decker RA. Update on the MEN 2A c804 RET mutation: is prophylactic thyroidectomy indicated?. Surgery. Dec 2000;128(6):1052-7;discussion 1057-8. [Medline].

  21. Garbrecht N, Anlauf M, Schmitt A, Henopp T, Sipos B, Raffel A, et al. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer. Mar 2008;15(1):229-41. [Medline].

  22. Georgitsi M, Raitila A, Karhu A, van der Luijt RB, Aalfs CM, Sane T, et al. Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. J Clin Endocrinol Metab. Aug 2007;92(8):3321-5. [Medline].

  23. Granberg D, Stridsberg M, Seensalu R, Eriksson B, Lundqvist G, Oberg K, et al. Plasma chromogranin A in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. Aug 1999;84(8):2712-7. [Medline].

  24. Grant F. Anesthetic considerations in the multiple endocrine neoplasia syndromes. Curr Opin Anaesthesiol. Jun 2005;18(3):345-52. [Medline].

  25. Gujral TS, van Veelen W, Richardson DS, Myers SM, Meens JA, Acton DS, et al. A novel RET kinase-beta-catenin signaling pathway contributes to tumorigenesis in thyroid carcinoma. Cancer Res. Mar 1 2008;68(5):1338-46. [Medline].

  26. Harrison B. Endocrine surgical aspects of multiple endocrine neoplasia syndromes in children. Horm Res. 2007;68 Suppl 5:105-6. [Medline].

  27. Hassett S, Costigan C, McDermott M, Fitzgerald RJ. Prophylactic thyroidectomy in the treatment of thyroid medullary carcinoma. Age for surgery?. Eur J Pediatr Surg. Oct 2000;10(5):334-6. [Medline].

  28. Huang SC, Koch CA, Vortmeyer AO, Pack SD, Lichtenauer UD, Mannan P, et al. Duplication of the mutant RET allele in trisomy 10 or loss of the wild-type allele in multiple endocrine neoplasia type 2-associated pheochromocytomas. Cancer Res. Nov 15 2000;60(22):6223-6. [Medline].

  29. Iler MA, King DR, Ginn-Pease ME, O'Dorisio TM, Sotos JF. Multiple endocrine neoplasia type 2A: a 25-year review. J Pediatr Surg. Jan 1999;34(1):92-6; discussion 96-7. [Medline].

  30. Imai Y, Fukase M, Tsutsumi M, Fukami T, Sakaguchi K, Furumoto M, et al. A case of multiple endocrine neoplasia type II b: endocrinological evaluation and family screening. Endocrinol Jpn. Feb 1982;29(1):49-56. [Medline].

  31. Johnston LB, Chew SL, Trainer PJ, Reznek R, Grossman AB, Besser GM, et al. Screening children at risk of developing inherited endocrine neoplasia syndromes. Clin Endocrinol (Oxf). Feb 2000;52(2):127-36. [Medline].

  32. Kameya T, Tsukada T, Yamaguchi K. Recent advances in MEN1 gene study for pituitary tumor pathogenesis. Front Horm Res. 2004;32:265-91. [Medline].

  33. Koch CA. Molecular pathogenesis of MEN2-associated tumors. Fam Cancer. 2005;4(1):3-7. [Medline].

  34. Koch CA, Pacak K, Chrousos GP. Endocrine tumors. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia, Pa: Lippincott Raven; 2006.

  35. Koch CA, Pacak K, Chrousos GP. The molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors. J Clin Endocrinol Metab. Dec 2002;87(12):5367-84. [Medline].

  36. Lim LC, Tan MH, Eng C, Teh BT, Rajasoorya RC. Thymic carcinoid in multiple endocrine neoplasia 1: genotype-phenotype correlation and prevention. J Intern Med. Apr 2006;259(4):428-32. [Medline].

  37. Lowney JK, Frisella MM, Lairmore TC, Doherty GM. Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: correlation with primary tumor size. Surgery. Dec 1998;124(6):1043-8, discussion 1048-9. [Medline].

  38. Mailman MD, Muscarella P, Schirmer WJ, Ellison EC, O'Dorisio TM, Prior TW. Identification of MEN1 mutations in sporadic enteropancreatic neuroendocrine tumors by analysis of paraffin-embedded tissue. Clin Chem. Jan 1999;45(1):29-34. [Medline].

  39. Marx S, Spiegel AM, Skarulis MC, Doppman JL, Collins FS, Liotta LA. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. Sep 15 1998;129(6):484-94. [Medline].

  40. Marx SJ. Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev Cancer. May 2005;5(5):367-75. [Medline].

  41. McCarthy PM, Piehler JM, Schaff HV, Pluth JR, Orszulak TA, Vidaillet HJ Jr, et al. The significance of multiple, recurrent, and "complex" cardiac myxomas. J Thorac Cardiovasc Surg. Mar 1986;91(3):389-96. [Medline].

  42. Miehle K, Kratzsch J, Lenders JW, Kluge R, Paschke R, Koch CA. Adrenal incidentaloma diagnosed as pheochromocytoma by plasma chromogranin A and plasma metanephrines. J Endocrinol Invest. Dec 2005;28(11):1040-2. [Medline].

  43. Neumann HP, Vortmeyer A, Schmidt D, Werner M, Erlic Z, Cascon A, et al. Evidence of MEN-2 in the original description of classic pheochromocytoma. N Engl J Med. Sep 27 2007;357(13):1311-5. [Medline].

  44. Norton JA, Fang TD, Jensen RT. Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1. J Natl Compr Canc Netw. Feb 2006;4(2):148-53. [Medline].

  45. O'Brien T, O'Riordan DS, Gharib H, Scheithauer BW, Ebersold MJ, van Heerden JA. Results of treatment of pituitary disease in multiple endocrine neoplasia, type I. Neurosurgery. Aug 1996;39(2):273-8; discussion 278-9. [Medline].

  46. Oberg K. Interferon in the management of neuroendocrine GEP-tumors: a review. Digestion. 2000;62 Suppl 1:92-7. [Medline].

  47. Ogilvie JB, Kebebew E. Indication and timing of thyroid surgery for patients with hereditary medullary thyroid cancer syndromes. J Natl Compr Canc Netw. Feb 2006;4(2):139-47. [Medline].

  48. Pacak K, Chrousos GP, Koch CA, et al. Pheochromocytoma: progress in diagnosis, therapy, and genetics. In: Margioris A, Chrousos GP, eds. Adrenal Disorders. Humana Press: Totowa, NJ; 2001.

  49. Parlowsky T, Bucsky P, Hof M, Kaatsch P. Malignant endocrine tumours in childhood and adolescence--results of a retrospective analysis. Klin Padiatr. Jul-Aug 1996;208(4):205-9. [Medline].

  50. Proye CA, Nguyen HH. Current perspectives in the surgery of multiple endocrine neoplasias. Aust N Z J Surg. Feb 1999;69(2):106-16. [Medline].

  51. Pujol RM, Matias-Guiu X, Miralles J, Colomer A, de Moragas JM. Multiple idiopathic mucosal neuromas: a minor form of multiple endocrine neoplasia type 2B or a new entity?. J Am Acad Dermatol. Aug 1997;37(2 Pt 2):349-52. [Medline].

  52. Ruszniewski P, Podevin P, Cadiot G, Marmuse JP, Mignon M, Vissuzaine C, et al. Clinical, anatomical, and evolutive features of patients with the Zollinger-Ellison syndrome combined with type I multiple endocrine neoplasia. Pancreas. May 1993;8(3):295-304. [Medline].

  53. Sakurai A, Uchino S, Takami H. Current status of clinical care for familial endocrine tumor syndromes in Japan. Endocr J. Dec 2005;52(6):757-62. [Medline].

  54. Scacheri PC, Davis S, Odom DT, Crawford GE, Perkins S, Halawi MJ, et al. Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet. Apr 2006;2(4):e51. [Medline].

  55. Scarsbrook AF, Thakker RV, Wass JA, Gleeson FV, Phillips RR. Multiple endocrine neoplasia: spectrum of radiologic appearances and discussion of a multitechnique imaging approach. Radiographics. Mar-Apr 2006;26(2):433-51. [Medline].

  56. Shan L, Nakamura Y, Nakamura M, Yokoi T, Tsujimoto M, Arima R, et al. Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors. Lab Invest. Apr 1998;78(4):471-5. [Medline].

  57. Skinner MA, DeBenedetti MK, Moley JF, Norton JA, Wells SA Jr. Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B. J Pediatr Surg. Jan 1996;31(1):177-81; discussion 181-2. [Medline].

  58. Skinner MA, Moley JA, Dilley WG, Owzar K, Debenedetti MK, Wells SA Jr. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. Sep 15 2005;353(11):1105-13. [Medline].

  59. Skinner MA, Wells SA Jr. Medullary carcinoma of the thyroid gland and the MEN 2 syndromes. Semin Pediatr Surg. Aug 1997;6(3):134-40. [Medline].

  60. Skogseid B, Doherty GM. Multiple endocrine neoplasia type 1: clinical and genetic features. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S131-4. [Medline].

  61. Stratakis CA. Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes. Front Biosci. Mar 1 2000;5:D353-66. [Medline].

  62. Stratakis CA, Schussheim DH, Freedman SM, Keil MF, Pack SD, Agarwal SK, et al. Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. Dec 2000;85(12):4776-80. [Medline].

  63. Tagge EP, Hill JG, Tagge DU, Macpherson R. Pancreatic surgery in children. Curr Opin Pediatr. Jun 1995;7(3):342-8. [Medline].

  64. Thomas-Marques L, Murat A, Delemer B, Penfornis A, Cardot-Bauters C, Baudin E, et al. Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am J Gastroenterol. Feb 2006;101(2):266-73. [Medline].

  65. Thompson NW. Management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1. Surg Oncol Clin N Am. Oct 1998;7(4):881-91. [Medline].

  66. Triponez F, Dosseh D, Goudet P, Cougard P, Bauters C, Murat A. Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg. Feb 2006;243(2):265-72. [Medline].

  67. Trouillas J, Labat-Moleur F, Sturm N, Kujas M, Heymann MF, Figarella-Branger D, et al. Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol. Apr 2008;32(4):534-43. [Medline].

  68. van Heurn LW, Schaap C, Sie G, Haagen AA, Gerver WJ, Freling G, et al. Predictive DNA testing for multiple endocrine neoplasia 2: a therapeutic challenge of prophylactic thyroidectomy in very young children. J Pediatr Surg. Apr 1999;34(4):568-71. [Medline].

  69. Vasen HF, Lamers CB, Lips CJ. Screening for the multiple endocrine neoplasia syndrome type I. A study of 11 kindreds in The Netherlands. Arch Intern Med. Dec 1989;149(12):2717-22. [Medline].

  70. Wang EH, Ebrahimi SA, Wu AY, Kashefi C, Passaro E Jr, Sawicki MP. Mutation of the MENIN gene in sporadic pancreatic endocrine tumors. Cancer Res. Oct 1 1998;58(19):4417-20. [Medline].

  71. Whelan T, Gatfield CT, Robertson S, Carpenter B, Schillinger JF. Primary carcinoid of the prostate in conjunction with multiple endocrine neoplasia IIb in a child. J Urol. Mar 1995;153(3 Pt 2):1080-2. [Medline].

  72. Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. Oct 1955;142(4):709-23; discussion, 724-8. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.