Wermer Syndrome (MEN Type 1) Treatment & Management

  • Author: Irina Lendel, MD; Chief Editor: George T Griffing, MD   more...
 
Updated: Oct 8, 2010
 

Medical Care

  • Hyperparathyroidism: Surgery is the treatment of choice. In patients who cannot undergo surgery, bisphosphonates may be useful. Calcium-sensing receptor agonists (calcimimetics), a novel class of drugs, have a potential role in the management of hyperparathyroidism associated with MEN 1 by directly reducing PTH release.[8]
  • Gastrinoma: Inhibition of acid hypersecretion is achieved with proton pump inhibitors. Metastatic gastrinoma may be treated with streptozocin and doxorubicin. Octreotide might decrease tumor progression; however, benefit is controversial.
  • Insulinoma: No curative long-term medical treatment exists for insulinomas. Surgical tumor removal is the treatment of choice.[9] Treat unresectable tumors with diazoxide. Long-acting somatostatin analogs can be useful in controlling hyperinsulinemia.
  • Glucagonomas: Surgical extirpation is indicated.
  • Vasoactive intestinal polypeptide tumor (VIPoma): Octreotide controls symptoms in 80% of cases, although surgical tumor removal should be attempted.
  • Prolactinomas: These are best treated with bromocriptine or other dopamine agonists.
  • Patients with symptomatic carcinoid tumors require somatostatin.
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Surgical Care

  • In general, surgery is indicated to control symptoms that are medically intractable and to prevent metastases of enteropancreatic neoplasms.[10]
  • Surgery is the treatment of choice for hyperparathyroidism in patients with MEN 1, if the following occur:
    • Serum albumin-adjusted calcium level is higher than 3 mmol/L (12 mg/dL).
    • Kidney stones are found.
    • PTH-induced bone disease, including osteoporosis, is present.
  • In patients with ZES/MEN 1, parathyroid surgery is favored by some even in milder forms of hypercalcemia because normal serum calcium levels are often associated with lower serum gastrin levels and, consequently, lower gastric acid secretion. However, recently, due to effective pharmacotherapy for ZES, it is not considered to be a significant indication for surgery.
  • For parathyroid hyperplasia, the 2 recommended surgical approaches are subtotal parathyroidectomy[11] (with removal of 3.5 parathyroid glands) and total parathyroidectomy (with removal of all 4 glands) and immediate autograft of parathyroid tissue into the musculature of the nondominant arm. The current approach seems to be shifting back to removal of 3.5 glands. Hypocalcemia is more frequent with total parathyroidectomy.
  • Surgeons should make careful operative notes and mark the residual parathyroid tissue with clips because reoperation is likely in patients with MEN 1. Recurrence is reported in 43% of patients at 10 years of follow-up.
  • At the time of parathyroidectomy, thymus might be removed to prevent carcinoid tumor.
  • With gastrinoma, the role of surgery in ZES and MEN 1 remains controversial because cure is achieved only occasionally.
    • 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. Removal of tumors larger than 2 cm in diameter reduces frequency of liver metastasis, which is an important prognostic factor.
    • Gastrinomas are found in the duodenal wall, the pancreas, or the 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. Surgery may also provide symptomatic relief in patients with large, locally metastatic tumors.
    • Resection of liver metastases may be beneficial.
    • Total pancreatectomy is not indicated because of the deleterious effects of this procedure (ie, pancreatic exocrine insufficiency and diabetes mellitus).
  • Insulinomas are most often single large tumors that can be enucleated. Resection may result in cure, although insulinomas in patients with MEN 1 may be multicentric and small. A problem in these familial cases is that the lesion detected radiologically may not be the one causing hypoglycemia. Insulin measurements in the portal or hepatic veins may be required to localize the insulin secretion.[9]
    • Some authors recommend subtotal pancreatectomy (80% or more 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.
  • Glucagonomas are similar to insulinomas, and resection of single glucagonomas most often results in cure.
  • For VIPomas, resection of single and multiple tumors is indicated, which may include a pancreatic tail resection.
  • In pituitary tumors, transsphenoidal pituitary surgery is aimed at resection of any pituitary mass, especially in acromegaly, Cushing, or nonfunctional tumors.
  • Prolactinomas may be large and multicentric. Patients with prolactinomas should continue treatment with dopamine agonists.
    • The recurrence rate after surgical removal is high.
    • Transsphenoidal surgery with external radiation therapy (eg, external beam or gamma knife) is indicated in patients in whom long-term dopamine agonist therapy becomes ineffective.
  • Carcinoid tumors are removed surgically; half of them are locally invasive or metastatic, particularly thymic carcinoids.[3]
  • For lipomas, local excision is the therapy of choice if troublesome symptoms are present.
  • For nonfunctioning pancreatic tumors, surgery might be considered for tumors larger than 2 cm, as tumor size correlates with risk of metastasis and death.
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Consultations

This is a process that involves many organ systems, and significant difficulties in diagnosis and management are associated with each system. Multiple consultations are generally necessary, including consultations with an endocrinologist, gastroenterologist, neurosurgeon, general surgeon, and dermatologist.

  • Endocrinologist - Evaluation and treatment of insulinoma, glucagonoma, hyperparathyroidism, Cushing syndrome, and acromegaly
  • Dermatologist - Evaluation of rash for specific patterns
  • Gastroenterologist - Evaluation and treatment of gastrinoma, VIPoma, PPoma, and carcinoid tumor
  • Neurosurgeon - Possible resection of growth hormone–producing macroadenoma; prolactin-producing microadenoma most often can be treated pharmacologically
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Contributor Information and Disclosures
Author

Irina Lendel, MD  Clinical Instructor in Endocrinology, Division of Endocrinology, Diabetes, and Metabolism, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

James M Hammond, MD  Distinguished Professor of Medicine, Penn State University College of Medicine, Milton S Hershey Medical Center

James M Hammond, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, American Federation for Clinical Research, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Phi Beta Kappa, and Society for the Study of Reproduction

Disclosure: Nothing to disclose.

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.

Specialty Editor Board

Frederick H Ziel, MD  Associate Professor of Medicine, David Geffen School of Medicine at UCLA; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS  Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law, Medicine & Ethics, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

References

  1. Eller-Vainicher C, Chiodini I, Battista C, et al. Sporadic and MEN 1 related primary hyperparathyroidism: differences in clinical expression and severity. J Bone Miner Res. Mar 23 2009;[Medline].

  2. Anlauf M, Perren A, Meyer CL, et al. Precursor lesions in patients with multiple endocrine neoplasia type 1-associated duodenal gastrinomas. Gastroenterology. May 2005;128(5):1187-98. [Medline].

  3. Ferolla P, Falchetti A, Filosso P, et al. Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series. J Clin Endocrinol Metab. May 2005;90(5):2603-9. [Medline]. [Full Text].

  4. Yip L, Ogilvie JB, Challinor SM, et al. Identification of multiple endocrine neoplasia type 1 in patients with apparent sporadic primary hyperparathyroidism. Surgery. Dec 2008;144(6):1002-6; discussion 1006-7. [Medline].

  5. Whitley SA, Moyes VJ, Park KM, et al. The appearance of the adrenal glands on computed tomography in multiple endocrine neoplasia type 1. Eur J Endocrinol. Dec 2008;159(6):819-24. [Medline].

  6. Tsukada T, Nagamura Y, Ohkura N. MEN1 gene and its mutations: basic and clinical implications. Cancer Sci. Dec 8 2008;[Medline].

  7. Waldmann J, Fendrich V, Habbe N, et al. Screening of patients with multiple endocrine neoplasia type 1 (MEN-1): a critical analysis of its value. World J Surg. Jun 2009;33(6):1208-18. [Medline].

  8. Hebert SC. Therapeutic use of calcimimetics. Annu Rev Med. 2006;57:349-64. [Medline].

  9. Tucker ON, Crotty PL, Conlon KC. The management of insulinoma. Br J Surg. Mar 2006;93(3):264-75. [Medline].

  10. Wilson SD, Krzywda EA, Zhu YR, et al. The influence of surgery in MEN-1 syndrome: observations over 150 years. Surgery. Oct 2008;144(4):695-701; discussion 701-2. [Medline].

  11. Hubbard JG, Sebag F, Maweja S, et al. Subtotal parathyroidectomy as an adequate treatment for primary hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg. Mar 2006;141(3):235-9. [Medline]. [Full Text].

  12. Asgharian B, Turner ML, Gibril F, Entsuah LK, Serrano J, Jensen RT. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J Clin Endocrinol Metab. Nov 2004;89(11):5328-36. [Medline].

  13. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. Dec 2001;86(12):5658-71. [Medline].

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

  15. Donow C, Pipeleers-Marichal M, Schroder S. Surgical pathology of gastrinoma. Site, size, multicentricity, association with multiple endocrine neoplasia type 1, and malignancy. Cancer. Sep 15 1991;68(6):1329-34. [Medline].

  16. Eriksson B, Bergstrom M, Orlefors H. 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. Granberg D, Stridsberg M, Seensalu R. Plasma chromogranin A in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. Aug 1999;84(8):2712-7. [Medline].

  19. Hausman MS Jr, Thompson NW, Gauger PG, Doherty GM. The surgical management of MEN-1 pancreatoduodenal neuroendocrine disease. Surgery. Dec 2004;136(6):1205-11.

  20. Katai M, Sakurai A, Inaba H, Ikeo Y, Yamauchi K, Hashizume K. Octreotide as a rapid and effective painkiller for metastatic carcinoid tumor. Endocr J. Apr 2005;52(2):277-80.

  21. Lairmore TC, Chen VY, DeBenedetti MK. Duodenopancreatic resections in patients with multiple endocrine neoplasia type 1. Ann Surg. Jun 2000;231(6):909-18. [Medline].

  22. Lairmore TC, Piersall LD, DeBenedetti MK, Dilley WG, Mutch MG, Whelan AJ. Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1). Ann Surg. May 2004;239(5):637-45; discussion 645-7.

  23. Lambert LA, Shapiro SE, Lee JE, Perrier ND, Truong M, Wallace MJ. Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Arch Surg. Apr 2005;140(4):374-82.

  24. Lowney JK, Frisella MM, Lairmore TC. 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].

  25. MacFarlane MP, Fraker DL, Alexander HR. Prospective study of surgical resection of duodenal and pancreatic gastrinomas in multiple endocrine neoplasia type 1. Surgery. Dec 1995;118(6):973-9; discussion 979-80. [Medline].

  26. Mailman MD, Muscarella P, Schirmer WJ. Identification of MEN1 mutations in sporadic enteropancreatic neuroendocrine tumors by analysis of paraffin-embedded tissue. Clin Chem. Jan 1999;45(1):29-34. [Medline].

  27. Norton JA, Cornelius MJ, Doppman JL. Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome, and multiple endocrine neoplasia type I: a prospective study. Surgery. Dec 1987;102(6):958-66. [Medline].

  28. Norton JA, Melcher ML, Gibril F, Jensen RT. Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment. Surgery. Dec 2004;136(6):1267-74.

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

  30. Phan GQ, Yeo CJ, Hruban RH. Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: review of 125 patients. J Gastrointest Surg. Sep-Oct 1998;2(5):472-82. [Medline].

  31. 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].

  32. Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. Jun 25 1992;326(26):1721-6. [Medline].

  33. Ruszniewski P, Podevin P, Cadiot G. 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].

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

  35. Silverberg SJ, Bone HG 3rd, Marriott TB, Locker FG, Thys-Jacobs S, Dziem G. Short-term inhibition of parathyroid hormone secretion by a calcium-receptor agonist in patients with primary hyperparathyroidism. N Engl J Med. Nov 20 1997;337(21):1506-10. [Medline].

  36. 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].

  37. Thompson NW. Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease. Results in the treatment of 40 patients with Zollinger-Ellison syndrome, hypoglycaemia or both. J Intern Med. Jun 1998;243(6):495-500. [Medline].

  38. 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].

  39. Triponez F, Dosseh D, Goudet P, et al. 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].

  40. Wang EH, Ebrahimi SA, Wu AY. Mutation of the MENIN gene in sporadic pancreatic endocrine tumors. Cancer Res. Oct 1 1998;58(19):4417-20. [Medline].

  41. Yano M, Fukai I, Kobayashi Y, et al. ACTH-secreting thymic carcinoid associated with multiple endocrine neoplasia type 1. Ann Thorac Surg. Jan 2006;81(1):366-8. [Medline].

  42. Yeo CJ. Islet cell tumors of the pancreas. In: Niederhuber JE, ed. Current Therapy in Oncology. St Louis, Mo: Mosby-Year Book; 1993:272.

  43. Yim JH, Siegel BA, DeBenedetti MK. Prospective study of the utility of somatostatin-receptor scintigraphy in the evaluation of patients with multiple endocrine neoplasia type 1. Surgery. Dec 1998;124(6):1037-42. [Medline].

 
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Sagittal (left image) and coronal (right image), T1-weighted magnetic resonance images of the brain in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1). These images show a pituitary macroadenoma (arrows).
Indium-111 (111In) octreotide scan in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1). These nuclear images demonstrate abnormal activity in the pituitary macroadenoma (curved arrow), parathyroid adenoma (straight arrow), and gastrinoma metastases throughout the abdomen (arrowheads).
Technetium-99m sestamibi scan (99mTc MIBI) in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1). These images demonstrate persistent abnormal activity of the inferior right parathyroid gland that is consistent with an adenoma.
Computed tomography (CT) scan of the pancreas in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and a gastrinoma. This image shows a pancreatic head mass (large, white arrow), as well as a low-attenuating lesion in the liver (small, black arrowhead) that indicates metastases. Note the calcifications of the right renal medullary pyramids (medullary nephrocalcinosis; black arrows) in this nonenhanced CT scan.
Endoscopic ultrasonogram in a patient with an insulinoma. The hypoechoic neoplasm (arrows) is seen in the body of the pancreas anterior to the splenic vein (SV). (From: Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. Jun 25 1992;326(26):1721-6.)
Computed tomography (CT) scan image with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the tail of the pancreas (P) posterior to the stomach (S) (From: Yeo CJ. Islet cell tumors of the pancreas. In: Niederhuber JE, ed. Current Therapy in Oncology. St. Louis, Mo: Mosby-Year Book; 1993: 272.)
Anteroposterior radiographic view of the right hand in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and primary hyperparathyroidism. This image shows subperiosteal bone resorption along the radial aspects of the middle phalanges (arrows).
Bilateral, anteroposterior radiographic views of the hands in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and primary hyperparathyroidism. These images show subperiosteal bone resorption along the radial aspects of the middle phalanges.
 
 
 
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