Multiple endocrine neoplasia type 1: Treatment
- Andrew Arnold, MD
Andrew Arnold, MD
- Murray-Heilig Professor of Molecular Medicine
- University of Connecticut
- Section Editors
- Peter J Snyder, MD
Peter J Snyder, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Male Reproductive Endocrinology
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Marc K Drezner, MD
Marc K Drezner, MD
- Section Editor — Bone Disease
- Professor of Medicine
- University of Wisconsin Medical School
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder classically characterized by predisposition to tumors of the parathyroid glands (which occur in nearly all patients by age 50 years), anterior pituitary, and pancreatic islet cells (table 1). MEN1 also includes a predisposition to gastrinomas in the duodenum, carcinoids, adrenal adenomas, angiofibromas, and lipomas (table 2). The tumors are generally benign, but malignancy of some carcinoid, islet cell, and gastrointestinal tract tumors are important causes of mortality in MEN1.
This topic will review the treatment of MEN1. The classification, genetics, clinical manifestations, and diagnosis are reviewed separately. (See "Multiple endocrine neoplasia type 1: Definition and genetics" and "Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis".)
Multiple parathyroid tumors causing primary hyperparathyroidism are the most common manifestation of MEN1, with over 90 percent penetrance by age 40 to 50 years . Multiple gland involvement is common in these patients and, given sufficient time, perhaps universal. Patients with classical MEN1 are at high risk of recurrent hyperparathyroidism after apparently successful subtotal parathyroidectomy.
Indications for surgery — Once the biochemical diagnosis of primary hyperparathyroidism is confirmed in a patient with known or presumed MEN1, the indications for surgical intervention are similar to those in patients with sporadic primary hyperparathyroidism. These include symptomatic or marked hypercalcemia, nephrolithiasis, and evidence of bone disease such as diminished bone density or fracture . Bone density of the lumbar spine and hip can improve after parathyroidectomy in patients with hyperparathyroidism associated with MEN1, as it does in patients with sporadic hyperparathyroidism . (See "Primary hyperparathyroidism: Management", section on 'Candidates for surgery'.)
An additional indication for parathyroidectomy in patients with MEN1 is the presence of severe peptic ulcer disease or other symptoms caused by a gastrinoma (the Zollinger-Ellison syndrome) that are difficult to control with medications. Hypercalcemia typically worsens hypergastrinemia, and parathyroidectomy may markedly reduce gastrin secretion in patients with a gastrinoma [4,5]. The typical high success of pharmacologic therapy for hypergastrinemia makes this a rare indication for operation.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Rizzoli R, Green J 3rd, Marx SJ. Primary hyperparathyroidism in familial multiple endocrine neoplasia type I. Long-term follow-up of serum calcium levels after parathyroidectomy. Am J Med 1985; 78:467.
- Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab 2012; 97:2990.
- Coutinho FL, Lourenço DM Jr, Toledo RA, et al. Bone mineral density analysis in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 after total parathyroidectomy. Clin Endocrinol (Oxf) 2010; 72:462.
- Mai HD, Sanowski RA. Regression of duodenal gastrinomas in a patient with multiple endocrine neoplasia type I after parathyroidectomy. Gastrointest Endosc 1992; 38:706.
- Norton JA, Venzon DJ, Berna MJ, et al. Prospective study of surgery for primary hyperparathyroidism (HPT) in multiple endocrine neoplasia-type 1 and Zollinger-Ellison syndrome: long-term outcome of a more virulent form of HPT. Ann Surg 2008; 247:501.
- Tonelli F, Marcucci T, Giudici F, et al. Surgical approach in hereditary hyperparathyroidism. Endocr J 2009; 56:827.
- Stålberg P, Carling T. Familial parathyroid tumors: diagnosis and management. World J Surg 2009; 33:2234.
- Schreinemakers JM, Pieterman CR, Scholten A, et al. The optimal surgical treatment for primary hyperparathyroidism in MEN1 patients: a systematic review. World J Surg 2011; 35:1993.
- Burgess JR, David R, Parameswaran V, et al. The outcome of subtotal parathyroidectomy for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1. Arch Surg 1998; 133:126.
- Carling T, Udelsman R. Parathyroid surgery in familial hyperparathyroid disorders. J Intern Med 2005; 257:27.
- O'Riordain DS, O'Brien T, Grant CS, et al. Surgical management of primary hyperparathyroidism in multiple endocrine neoplasia types 1 and 2. Surgery 1993; 114:1031.
- Hellman P, Skogseid B, Juhlin C, et al. Findings and long-term results of parathyroid surgery in multiple endocrine neoplasia type 1. World J Surg 1992; 16:718.
- Baumann DS, Wells SA Jr. Parathyroid autotransplantation. Surgery 1993; 113:130.
- Cohen MS, Dilley WG, Wells SA Jr, et al. Long-term functionality of cryopreserved parathyroid autografts: a 13-year prospective analysis. Surgery 2005; 138:1033.
- Tonelli F, Marcucci T, Fratini G, et al. Is total parathyroidectomy the treatment of choice for hyperparathyroidism in multiple endocrine neoplasia type 1? Ann Surg 2007; 246:1075.
- Powell AC, Alexander HR, Pingpank JF, et al. The utility of routine transcervical thymectomy for multiple endocrine neoplasia 1-related hyperparathyroidism. Surgery 2008; 144:878.
- Goudet P, Murat A, Cardot-Bauters C, et al. Thymic neuroendocrine tumors in multiple endocrine neoplasia type 1: a comparative study on 21 cases among a series of 761 MEN1 from the GTE (Groupe des Tumeurs Endocrines). World J Surg 2009; 33:1197.
- Moyes VJ, Monson JP, Chew SL, Akker SA. Clinical Use of Cinacalcet in MEN1 Hyperparathyroidism. Int J Endocrinol 2010; 2010:906163.
- Falchetti A, Cilotti A, Vaggelli L, et al. A patient with MEN1-associated hyperparathyroidism, responsive to cinacalcet. Nat Clin Pract Endocrinol Metab 2008; 4:351.
- Giusti F, Cianferotti L, Gronchi G, et al. Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to Multiple Endocrine Neoplasia Syndrome type 1 (MEN1). Endocrine 2016; 52:495.
- Akerström G, Johansson H, Grama D. Surgical treatment of endocrine pancreatic lesions in MEN-1. Acta Oncol 1991; 30:541.
- Sheppard BC, Norton JA, Doppman JL, et al. Management of islet cell tumors in patients with multiple endocrine neoplasia: a prospective study. Surgery 1989; 106:1108.
- Pipeleers-Marichal M, Somers G, Willems G, et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N Engl J Med 1990; 322:723.
- Ito T, Igarashi H, Jensen RT. Zollinger-Ellison syndrome: recent advances and controversies. Curr Opin Gastroenterol 2013; 29:650.
- Norton JA, Fraker DL, Alexander HR, et al. Surgery increases survival in patients with gastrinoma. Ann Surg 2006; 244:410.
- Gauger PG, Doherty GM, Broome JT, et al. Completion pancreatectomy and duodenectomy for recurrent MEN-1 pancreaticoduodenal endocrine neoplasms. Surgery 2009; 146:801.
- Libutti SK, Alexander HR Jr. Gastrinoma: sporadic and familial disease. Surg Oncol Clin N Am 2006; 15:479.
- Doherty GM. Commentary on "Better Survival But Changing Causes of Death in Patients With Multiple Endocrine Neoplasia Type 1". Ann Surg 2015; 261:e149.
- 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 1998; 243:495.
- Fraker DL, Alexander HR. The surgical approach to endocrine tumors of the pancreas. Semin Gastrointest Dis 1995; 6:102.
- Doherty GM. Multiple endocrine neoplasia type 1. J Surg Oncol 2005; 89:143.
- Tonelli F, Fratini G, Nesi G, et al. Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias. Ann Surg 2006; 244:61.
- Norton JA, Fraker DL, Alexander HR, et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999; 341:635.
- Hausman MS Jr, Thompson NW, Gauger PG, Doherty GM. The surgical management of MEN-1 pancreatoduodenal neuroendocrine disease. Surgery 2004; 136:1205.
- Wamsteker EJ, Gauger PG, Thompson NW, Scheiman JM. EUS detection of pancreatic endocrine tumors in asymptomatic patients with type 1 multiple endocrine neoplasia. Gastrointest Endosc 2003; 58:531.
- Imamura M, Komoto I, Ota S, et al. Biochemically curative surgery for gastrinoma in multiple endocrine neoplasia type 1 patients. World J Gastroenterol 2011; 17:1343.
- Ito T, Lee L, Jensen RT. Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies. Expert Opin Pharmacother 2016; 17:2191.
- Metz DC, Strader DB, Orbuch M, et al. Use of omeprazole in Zollinger-Ellison syndrome: a prospective nine-year study of efficacy and safety. Aliment Pharmacol Ther 1993; 7:597.
- Demeure MJ, Klonoff DC, Karam JH, et al. Insulinomas associated with multiple endocrine neoplasia type I: the need for a different surgical approach. Surgery 1991; 110:998.
- Sadowski SM, Triponez F. Management of pancreatic neuroendocrine tumors in patients with MEN 1. Gland Surg 2015; 4:63.
- Dean PG, van Heerden JA, Farley DR, et al. Are patients with multiple endocrine neoplasia type I prone to premature death? World J Surg 2000; 24:1437.
- Geerdink EA, Van der Luijt RB, Lips CJ. Do patients with multiple endocrine neoplasia syndrome type 1 benefit from periodical screening? Eur J Endocrinol 2003; 149:577.
- Goudet P, Murat A, Binquet C, et al. Risk factors and causes of death in MEN1 disease. A GTE (Groupe d'Etude des Tumeurs Endocrines) cohort study among 758 patients. World J Surg 2010; 34:249.
- 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 2009; 33:1208.
- PARATHYROID TUMORS
- Indications for surgery
- Management of asymptomatic disease
- Preoperative localization
- Surgical approach
- Medical management
- PITUITARY ADENOMAS
- PANCREATIC ISLET CELL/GASTROINTESTINAL TUMORS
- Zollinger-Ellison syndrome
- - General therapeutic considerations
- - Pharmacologic treatment
- - Surgery
- Clinically nonfunctional pancreatic endocrine tumors
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS