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Multiple endocrine neoplasia

Reviewed April 2006

What is multiple endocrine neoplasia?

Multiple endocrine neoplasia is part of a group of disorders that affect the body's network of hormone-producing glands (the endocrine system). Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia involves tumors in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, some cases can be life-threatening.

The two major forms of multiple endocrine neoplasia are called type 1 and type 2; they are often confused because of their similar names. Type 1 and type 2 are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.

Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid gland, pituitary gland, and pancreas. Tumors in these glands lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid gland (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.

The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is a tumor of the adrenal glands that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B, and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A. The features of this disorder are relatively consistent within any one family.

How common is multiple endocrine neoplasia?

Each of the two major types of multiple endocrine neoplasia affects an estimated 1 in 30,000 people. Among the subtypes of multiple endocrine neoplasia type 2, type 2A is the most common form, followed by familial medullary thyroid cancer. Type 2B is relatively uncommon, accounting for about 5 percent of all cases of multiple endocrine neoplasia type 2.

What genes are related to multiple endocrine neoplasia?

Mutations in the MEN1 and RET genes cause multiple endocrine neoplasia.

Mutations in the MEN1 gene cause multiple endocrine neoplasia type 1. This gene provides instructions for producing a protein called menin. Menin acts as a tumor suppressor, which means it normally keeps cells from growing and dividing too rapidly or in an uncontrolled way. Although the exact function of menin is unknown, it is likely involved in cell functions such as copying and repairing DNA and regulating the activity of other genes. If mutations inactivate both copies of the MEN1 gene, it is no longer able to control cell growth and division. The loss of functional menin allows cells to divide too frequently, leading to the formation of tumors characteristic of multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 2 results from mutations in the RET gene. This gene provides instructions for producing a protein that is involved in signaling within cells. The RET protein triggers chemical reactions that instruct cells to respond to their environment, for example by dividing or maturing. Mutations in the RET gene overactivate the protein's signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in endocrine glands and other tissues.

How do people inherit multiple endocrine neoplasia?

Most cases of multiple endocrine neoplasia type 1 are considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the MEN1 gene in each cell. In most cases, the altered gene is inherited from an affected parent. The remaining cases are a result of new mutations in the MEN1 gene, and occur in people with no history of the disorder in their family.

Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the MEN1 gene must be altered to trigger tumor formation in multiple endocrine neoplasia type 1. A mutation in the second copy of the MEN1 gene occurs in a small number of cells during a person's lifetime. Almost everyone who is born with one MEN1 mutation acquires a second mutation in certain cells and develops tumors of the endocrine glands and other tissues.

Multiple endocrine neoplasia type 2 is also usually inherited in an autosomal dominant pattern. A person with multiple endocrine neoplasia type 2 often inherits the altered RET gene from one parent with the condition. Some cases, however, result from new mutations in the gene and occur in people without other affected family members.

Where can I find information about treatment for multiple endocrine neoplasia?

You may find information on treatment or management of multiple endocrine neoplasia or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about multiple endocrine neoplasia?

You may find the following resources about multiple endocrine neoplasia helpful. These materials are written for the general public.

  • MedlinePlus - Health information
    • Encyclopedia: Medullary Carcinoma of Thyroid (http://www.nlm.nih.gov/medlineplus/ency/article/000374.htm)
    • Encyclopedia: Multiple Endocrine Neoplasia (MEN) I (http://www.nlm.nih.gov/medlineplus/ency/article/000398.htm)
    • Encyclopedia: Multiple Endocrine Neoplasia (MEN) II (http://www.nlm.nih.gov/medlineplus/ency/article/000399.htm)
    • Encyclopedia: Pancreatic Islet Cell Tumor (http://www.nlm.nih.gov/medlineplus/ency/article/000393.htm)
    • Encyclopedia: Pheochromocytoma (http://www.nlm.nih.gov/medlineplus/ency/article/000340.htm)
    • Encyclopedia: Pituitary Tumor (http://www.nlm.nih.gov/medlineplus/ency/article/000704.htm)
    • Encyclopedia: Primary Hyperparathyroidism (http://www.nlm.nih.gov/medlineplus/ency/article/000384.htm)
    • Health Topic: Endocrine Diseases (http://www.nlm.nih.gov/medlineplus/endocrinediseases.html)
    • Health Topic: Parathyroid Disorders (http://www.nlm.nih.gov/medlineplus/parathyroiddisorders.html)
    • Health Topic: Pheochromocytoma (http://www.nlm.nih.gov/medlineplus/pheochromocytoma.html)
    • Health Topic: Thyroid Cancer (http://www.nlm.nih.gov/medlineplus/thyroidcancer.html)
  • Additional NIH Resources - National Institutes of Health
    • National Cancer Institute: Genetics of Medullary Thyroid Cancer (PDQ) (http://www.cancer.gov/cancertopics/pdq/genetics/medullarythyroid/HealthProfessional/page2)
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.138)
    • National Institute of Diabetes and Digestive and Kidney Diseases: Hyperparathyroidism (http://endocrine.niddk.nih.gov/pubs/hyper/hyper.htm)
    • National Institute of Diabetes and Digestive and Kidney Diseases: Multiple Endocrine Neoplasia Type 1 (http://endocrine.niddk.nih.gov/pubs/men1/men1.htm)
  • Educational resources - Information pages
    • Mayo Clinic (http://www.mayoclinic.org/men1/)
    • Merck Manual of Medical Information, Second Home Edition (http://www.merck.com/mmhe/sec13/ch167/ch167a.html)
    • New York Online Access to Health (http://www.noah-health.org/en/endocrine/endocrine/neoplasia.html)
    • Orphanet: Multiple Endocrine Neoplasia Type 1 (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=652)
    • Orphanet: Multiple Endocrine Neoplasia Type 2 (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=653)
    • Stanford Cancer Center (http://cancer.stanford.edu/endocrine/)
    • University of Texas M. D. Anderson Cancer Center: Multiple Endocrine Neoplasia Type 1 (http://www.mdanderson.org/diseases/men/display.cfm?id=b75faf40-08d8-4d20-92359c1ed244d835&method=displayfull)
    • University of Texas M. D. Anderson Cancer Center: Multiple Endocrine Neoplasia Type 2 (http://www.mdanderson.org/diseases/men/display.cfm?id=c26bc4be-da65-458c-8943e0dd3d1cce05&method=displayfull)
  • Patient support - For patients and families
    • American Cancer Society (http://www.cancer.org/)
    • Directory of Endocrine and Metabolic Diseases Organizations (http://endocrine.niddk.nih.gov/resources/organizations.htm)
    • Johns Hopkins Thyroid Tumor Center (Thyroid-Cancer.net) (http://www.thyroid-cancer.net/topics/what+is+multiple+endocrine+neoplasia+(MEN))
    • New York Thyroid Center (http://cpmcnet.columbia.edu/dept/thyroid/)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/endocrin.html)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary
    • Gene Review: Multiple Endocrine Neoplasia Type 1 (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=men1)
    • Gene Review: Multiple Endocrine Neoplasia Type 2 (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=men2)
  • Gene Tests - DNA tests ordered by healthcare professionals
    • Gene Tests: Multiple Endocrine Neoplasia Type 1 (http://www.genetests.org/query?testid=2073)
    • Gene Tests: Multiple Endocrine Neoplasia Type 2 (http://www.genetests.org/query?testid=2137)
  • Genetic Tools - Teaching cases (http://www.genetests.org/servlet/access?fcn=y&filename=/tools/cases/mtc-29/)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22multiple+endocrine+neoplasia%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Multiple+Endocrine+Neoplasia[MAJR])+AND+(multiple+endocrine+neoplasia[TI])+AND+review[pt]+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1800+Days)
  • Online Books - Medical and science texts
    • Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Multiple Endocrine Neoplasia Type 1 (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=43)
    • Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Multiple Endocrine Neoplasia Type 2 (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=42)
  • OMIM - Genetic disorder catalog
    • OMIM topic: Multiple endocrine neoplasia I (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=131100)
    • OMIM topic: Multiple endocrine neoplasia IIA (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=171400)
    • OMIM topic: Multiple endocrine neoplasia IIB (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=162300)
    • OMIM topic: Thyroid carcinoma, familial medullary (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155240)

What other names do people use for multiple endocrine neoplasia?

  • Adenomatosis, Familial Endocrine
  • Endocrine Neoplasia, Multiple
  • Familial Endocrine Adenomatosis
  • MEA
  • MEN
  • Multiple Endocrine Adenomatosis
  • Multiple Endocrine Neoplasms

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about multiple endocrine neoplasia?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding multiple endocrine neoplasia?

adrenal glands ; autosomal ; autosomal dominant ; benign ; calcium ; cancer ; carcinoma ; cell ; cell division ; DNA ; endocrine gland ; endocrine system ; familial ; gene ; hormone ; hyperparathyroidism ; hypertension ; inheritance ; kidney ; kidney stones ; medullary thyroid cancer ; medullary thyroid carcinoma ; mucosa ; mutation ; neoplasia ; neoplasms ; neuroma ; new mutation ; pancreas ; parathyroid ; parathyroid gland ; pattern of inheritance ; pheochromocytoma ; pituitary gland ; protein ; sign ; stone ; symptom ; syndrome ; thyroid ; tissue ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References
  • Agarwal SK, Kennedy PA, Scacheri PC, Novotny EA, Hickman AB, Cerrato A, Rice TS, Moore JB, Rao S, Ji Y, Mateo C, Libutti SK, Oliver B, Chandrasekharappa SC, Burns AL, Collins FS, Spiegel AM, Marx SJ. Menin molecular interactions: insights into normal functions and tumorigenesis. Horm Metab Res. 2005 Jun;37(6):369-74. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16001329)
  • Bordi C. Multiple endocrine neoplasia (MEN)-associated tumours. Dig Liver Dis. 2004 Feb;36 Suppl 1:S31-4. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15077909)
  • Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001 Dec;86(12):5658-71. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=11739416)
  • Cardinal JW, Bergman L, Hayward N, Sweet A, Warner J, Marks L, Learoyd D, Dwight T, Robinson B, Epstein M, Smith M, Teh BT, Cameron DP, Prins JB. A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing. J Med Genet. 2005 Jan;42(1):69-74. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15635078)
  • Gertner ME, Kebebew E. Multiple endocrine neoplasia type 2. Curr Treat Options Oncol. 2004 Aug;5(4):315-25. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15233908)
  • Glascock MJ, Carty SE. Multiple endocrine neoplasia type 1: fresh perspective on clinical features and penetrance. Surg Oncol. 2002 Nov;11(3):143-50. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12356510)
  • Kouvaraki MA, Shapiro SE, Perrier ND, Cote GJ, Gagel RF, Hoff AO, Sherman SI, Lee JE, Evans DB. RET proto-oncogene: a review and update of genotype-phenotype correlations in hereditary medullary thyroid cancer and associated endocrine tumors. Thyroid. 2005 Jun;15(6):531-44. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16029119)
  • Marx SJ, Stratakis CA. Multiple endocrine neoplasia--introduction. J Intern Med. 2005 Jan;257(1):2-5. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15606371)
  • Marx SJ. Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev Cancer. 2005 May;5(5):367-75. Review. Erratum in: Nat Rev Cancer. 2005 Aug;5(8):663. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15864278)
  • Peczkowska M, Januszewicz A. Multiple endocrine neoplasia type 2. Fam Cancer. 2005;4(1):25-36. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15883707)
  • Scriver, Charles R; The metabolic & molecular bases of inherited disease; 8th ed.; New York : McGraw-Hill, c2001. p931-965.

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2006
Published: January 23, 2009