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Multiple endocrine neoplasia, type 1(MEN1)

MedGen UID:
9957
Concept ID:
C0025267
Neoplastic Process
Synonyms: Endocrine adenomatosis multiple; MEA I; MEN 1; MEN I; MEN1; Wermer syndrome
SNOMED CT: MEN 1 - Multiple endocrine neoplasia syndrome type 1 (30664006); MEN 1 syndrome (30664006); Multiple endocrine neoplasia syndrome type 1 (30664006); Multiple endocrine neoplasia, type 1 (30664006); MEN, type 1 (30664006); Wermer syndrome (30664006); MEA, type 1 (30664006); Multiple endocrine adenomatosis, type 1 (30664006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): MEN1 (11q13.1)
 
Monarch Initiative: MONDO:0007540
OMIM®: 131100
Orphanet: ORPHA652

Disease characteristics

Excerpted from the GeneReview: Multiple Endocrine Neoplasia Type 1
Multiple endocrine neoplasia type 1 (MEN1) includes varying combinations of more than 20 endocrine and non-endocrine tumors. Endocrine tumors become evident either by overproduction of hormones by the tumor or by growth of the tumor itself. Parathyroid tumors are the most common MEN1-associated endocrinopathy; onset in 90% of individuals is between ages 20 and 25 years with hypercalcemia evident by age 50 years; hypercalcemia causes lethargy, depression, confusion, anorexia, constipation, nausea, vomiting, diuresis, dehydration, hypercalciuria, kidney stones, increased bone resorption/fracture risk, hypertension, and shortened QT interval. Pituitary tumors include prolactinoma (the most common), which manifests as oligomenorrhea/amenorrhea and galactorrhea in females and sexual dysfunction in males. Well-differentiated endocrine tumors of the gastroenteropancreatic (GEP) tract can manifest as Zollinger-Ellison syndrome (gastrinoma); hypoglycemia (insulinoma); hyperglycemia, anorexia, glossitis, anemia, diarrhea, venous thrombosis, and skin rash (glucagonoma); and watery diarrhea, hypokalemia, and achlorhydria syndrome (vasoactive intestinal peptide [VIP]-secreting tumor). Carcinoid tumors are non-hormone-secreting and can manifest as a large mass after age 50 years. Adrenocortical tumors can be associated with primary hypercortisolism or hyperaldosteronism. Non-endocrine tumors include facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas. [from GeneReviews]
Authors:
Francesca Giusti  |  Francesca Marini  |  Maria Luisa Brandi   view full author information

Additional descriptions

From OMIM
Multiple endocrine neoplasia type I (MEN1) is an autosomal dominant disorder characterized by varying combinations of tumors of parathyroids, pancreatic islets, duodenal endocrine cells, and the anterior pituitary, with 94% penetrance by age 50. Less commonly associated tumors include foregut carcinoids, lipomas, angiofibromas, thyroid adenomas, adrenocortical adenomas, angiomyolipomas, and spinal cord ependymomas. Except for gastrinomas, most of the tumors are nonmetastasizing, but many can create striking clinical effects because of the secretion of endocrine substances such as gastrin, insulin, parathyroid hormone, prolactin, growth hormone, glucagon, or adrenocorticotropic hormone (summary by Chandrasekharappa et al., 1997). Familial isolated hyperparathyroidism (see 145000) occasionally results from the incomplete expression of MEN1 (summary by Simonds et al., 2004). Genetic Heterogeneity of Multiple Endocrine Neoplasia Other forms of multiple endocrine neoplasia include MEN2A (171400) and MEN2B (162300), both of which are caused by mutation in the RET gene (164761), and MEN4 (610755), which is caused by mutation in the CDKN1B gene (600778).  http://www.omim.org/entry/131100
From MedlinePlus Genetics
Multiple endocrine neoplasia is a group of disorders that affect the body's network of hormone-producing glands called 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 typically involves tumors (neoplasia) 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, the condition can be life-threatening.

The major forms of multiple endocrine neoplasia are called type 1, type 2, and type 4. These types 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 glands, the pituitary gland, and the pancreas. Tumors in these glands can lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid glands (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 an adrenal gland tumor that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B (formerly called type 3), 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, and medullary thyroid carcinoma is the only feature of FMTC. The signs and symptoms of multiple endocrine neoplasia type 2 are relatively consistent within any one family.

Multiple endocrine neoplasia type 4 appears to have signs and symptoms similar to those of type 1, although it is caused by mutations in a different gene. Hyperparathyroidism is the most common feature, followed by tumors of the pituitary gland, additional endocrine glands, and other organs.  https://medlineplus.gov/genetics/condition/multiple-endocrine-neoplasia

Clinical features

From HPO
Carcinoid tumor
MedGen UID:
2838
Concept ID:
C0007095
Neoplastic Process
A tumor formed from the endocrine (argentaffin) cells of the mucosal lining of a variety of organs including the stomach and intestine. These cells are from neuroectodermal origin.
Glucagonoma syndrome
MedGen UID:
4908
Concept ID:
C0017689
Neoplastic Process
An endocrine tumor of the pancreas that secretes excessive amounts of glucagon.
Pancreatic insulinoma
MedGen UID:
43907
Concept ID:
C0021670
Neoplastic Process
A type of tumor of the pancreatic beta cells that secretes excess insulin and can result in hypoglycemia.
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis (anterior pituitary).
Prolactin-producing pituitary gland adenoma
MedGen UID:
10936
Concept ID:
C0033375
Neoplastic Process
AIP familial isolated pituitary adenoma (AIP-FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and nonfunctioning pituitary adenomas (NFPA). Rarely TSH-secreting adenomas (thyrotropinomas) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-FIPA is usually in the second or third decade.
Thyroid adenoma
MedGen UID:
56228
Concept ID:
C0151468
Neoplastic Process
The presence of a adenoma of the thyroid gland.
Adrenocortical adenoma
MedGen UID:
61654
Concept ID:
C0206667
Neoplastic Process
Adrenocortical adenomas are benign tumors of the adrenal cortex.
Parathyroid gland adenoma
MedGen UID:
75502
Concept ID:
C0262587
Neoplastic Process
A benign tumor of the parathyroid gland that can cause hyperparathyroidism.
Subcutaneous lipoma
MedGen UID:
234674
Concept ID:
C1403035
Neoplastic Process
The presence of subcutaneous lipoma.
Pancreatic islet cell adenoma
MedGen UID:
342066
Concept ID:
C1851697
Neoplastic Process
The presence of an adenoma of the pancreas with origin in a pancreatic B cell.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Esophagitis
MedGen UID:
4549
Concept ID:
C0014868
Disease or Syndrome
Inflammation of the esophagus.
Peptic ulcer
MedGen UID:
45384
Concept ID:
C0030920
Disease or Syndrome
The term peptic ulcer refers to acid peptic injury of the digestive tract, resulting in mucosal break reaching the submucosa. Peptic ulcers are usually located in the stomach or proximal duodenum, but they can also be found in the esophagus or Meckel's diverticulum. Infection with Helicobacter pylori and the use of non steroidal antiinflammatory drugs (NSAIDs) or aspirin are the main risk factors of both gastric and duodenal peptic ulcers.
Zollinger-Ellison syndrome
MedGen UID:
53129
Concept ID:
C0043515
Disease or Syndrome
A condition in which there is increased production of gastrin by a gastrin-secreting tumor (usually located in the pancreas, duodenum, or abdominal lymph nodes) that stimulates the gastric mucosa to maximal activity, with consequent gastrointestinal mucosal ulceration.
Increased circulating prolactin concentration
MedGen UID:
1702649
Concept ID:
C5200994
Finding
The presence of abnormally increased levels of prolactin in the blood. Prolactin is a peptide hormone produced by the anterior pituitary gland that plays a role in breast development and lactation during pregnancy.
Hypercalcemia
MedGen UID:
5686
Concept ID:
C0020437
Disease or Syndrome
An abnormally increased calcium concentration in the blood.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Adenoma sebaceum
MedGen UID:
75563
Concept ID:
C0265319
Neoplastic Process
The presence of a sebaceous adenoma with origin in the sebum secreting cells of the skin.
Cafe-au-lait spot
MedGen UID:
113157
Concept ID:
C0221263
Finding
Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children.
Confetti-like hypopigmented macules
MedGen UID:
377093
Concept ID:
C1851705
Finding
Elevated circulating growth hormone concentration
MedGen UID:
66732
Concept ID:
C0235986
Finding
Acromegaly is a condition resulting from overproduction of growth hormone by the pituitary gland in persons with closed epiphyses, and consists chiefly in the enlargement of the distal parts of the body. The circumference of the skull increases, the nose becomes broad, the tongue becomes enlarged, the facial features become coarsened, the mandible grows excessively, and the teeth become separated. The fingers and toes grow chiefly in thickness.
Increased circulating cortisol level
MedGen UID:
871175
Concept ID:
C4025651
Finding
Overproduction of the hormone of cortisol by the adrenal cortex, resulting in a characteristic combination of clinical symptoms termed Cushing syndrome, with truncal obesity, a round, full face, striae atrophicae and acne, muscle weakness, and other features.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMultiple endocrine neoplasia, type 1
Follow this link to review classifications for Multiple endocrine neoplasia, type 1 in Orphanet.

Professional guidelines

PubMed

Norton JA, Foster DS, Ito T, Jensen RT
Endocrinol Metab Clin North Am 2018 Sep;47(3):577-601. doi: 10.1016/j.ecl.2018.04.009. PMID: 30098717Free PMC Article
Sato Y, Hashimoto S, Mizuno K, Takeuchi M, Terai S
World J Gastroenterol 2016 Aug 14;22(30):6817-28. doi: 10.3748/wjg.v22.i30.6817. PMID: 27570419Free PMC Article
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML; Endocrine Society
J Clin Endocrinol Metab 2012 Sep;97(9):2990-3011. Epub 2012 Jun 20 doi: 10.1210/jc.2012-1230. PMID: 22723327

Curated

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Neuroendocrine and Adrenal Tumors, 2023

Recent clinical studies

Etiology

Majer AD, Hua X, Katona BW
Genes (Basel) 2024 Sep 21;15(9) doi: 10.3390/genes15091231. PMID: 39336822Free PMC Article
Christ E, Iacovazzo D, Korbonits M, Perren A
Endocr Relat Cancer 2023 Jun 1;30(6) Epub 2023 May 16 doi: 10.1530/ERC-22-0327. PMID: 36952647
Pieterman CRC, Valk GD
Clin Endocrinol (Oxf) 2022 Oct;97(4):409-423. Epub 2022 Apr 1 doi: 10.1111/cen.14727. PMID: 35319130Free PMC Article
Rossi RE, Elvevi A, Citterio D, Coppa J, Invernizzi P, Mazzaferro V, Massironi S
World J Gastroenterol 2021 Sep 21;27(35):5890-5907. doi: 10.3748/wjg.v27.i35.5890. PMID: 34629807Free PMC Article
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML; Endocrine Society
J Clin Endocrinol Metab 2012 Sep;97(9):2990-3011. Epub 2012 Jun 20 doi: 10.1210/jc.2012-1230. PMID: 22723327

Diagnosis

Pieterman CRC, Valk GD
Clin Endocrinol (Oxf) 2022 Oct;97(4):409-423. Epub 2022 Apr 1 doi: 10.1111/cen.14727. PMID: 35319130Free PMC Article
Al-Salameh A, Cadiot G, Calender A, Goudet P, Chanson P
Nat Rev Endocrinol 2021 Apr;17(4):207-224. Epub 2021 Feb 9 doi: 10.1038/s41574-021-00468-3. PMID: 33564173
Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV
Endocr Rev 2021 Mar 15;42(2):133-170. doi: 10.1210/endrev/bnaa031. PMID: 33249439Free PMC Article
Niederle B, Selberherr A, Bartsch DK, Brandi ML, Doherty GM, Falconi M, Goudet P, Halfdanarson TR, Ito T, Jensen RT, Larghi A, Lee L, Öberg K, Pavel M, Perren A, Sadowski SM, Tonelli F, Triponez F, Valk GD, O'Toole D, Scott-Coombes D, Thakker RV, Thompson GB, Treglia G, Wiedenmann B
Neuroendocrinology 2021;111(7):609-630. Epub 2020 Sep 24 doi: 10.1159/000511791. PMID: 32971521
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML; Endocrine Society
J Clin Endocrinol Metab 2012 Sep;97(9):2990-3011. Epub 2012 Jun 20 doi: 10.1210/jc.2012-1230. PMID: 22723327

Therapy

Hofland J, Refardt JC, Feelders RA, Christ E, de Herder WW
J Clin Endocrinol Metab 2024 Mar 15;109(4):1109-1118. doi: 10.1210/clinem/dgad641. PMID: 37925662Free PMC Article
Jha S, Simonds WF
Endocr Rev 2023 Sep 15;44(5):779-818. doi: 10.1210/endrev/bnad009. PMID: 36961765Free PMC Article
Ito T, Lee L, Jensen RT
Expert Opin Pharmacother 2016 Nov;17(16):2191-2205. Epub 2016 Sep 23 doi: 10.1080/14656566.2016.1236916. PMID: 27635672Free PMC Article
Ito T, Igarashi H, Uehara H, Jensen RT
Expert Opin Pharmacother 2013 Feb;14(3):307-21. Epub 2013 Jan 30 doi: 10.1517/14656566.2013.767332. PMID: 23363383Free PMC Article
White ML, Doherty GM
Surg Oncol Clin N Am 2008 Apr;17(2):439-59, x. doi: 10.1016/j.soc.2007.12.002. PMID: 18375361

Prognosis

Siegel RL, Miller KD, Wagle NS, Jemal A
CA Cancer J Clin 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763. PMID: 36633525
Pieterman CRC, Valk GD
Clin Endocrinol (Oxf) 2022 Oct;97(4):409-423. Epub 2022 Apr 1 doi: 10.1111/cen.14727. PMID: 35319130Free PMC Article
Al-Salameh A, Cadiot G, Calender A, Goudet P, Chanson P
Nat Rev Endocrinol 2021 Apr;17(4):207-224. Epub 2021 Feb 9 doi: 10.1038/s41574-021-00468-3. PMID: 33564173
Niederle B, Selberherr A, Bartsch DK, Brandi ML, Doherty GM, Falconi M, Goudet P, Halfdanarson TR, Ito T, Jensen RT, Larghi A, Lee L, Öberg K, Pavel M, Perren A, Sadowski SM, Tonelli F, Triponez F, Valk GD, O'Toole D, Scott-Coombes D, Thakker RV, Thompson GB, Treglia G, Wiedenmann B
Neuroendocrinology 2021;111(7):609-630. Epub 2020 Sep 24 doi: 10.1159/000511791. PMID: 32971521
Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML; Endocrine Society
J Clin Endocrinol Metab 2012 Sep;97(9):2990-3011. Epub 2012 Jun 20 doi: 10.1210/jc.2012-1230. PMID: 22723327

Clinical prediction guides

Simonds WF
Front Endocrinol (Lausanne) 2023;14:1183297. Epub 2023 Jun 20 doi: 10.3389/fendo.2023.1183297. PMID: 37409236Free PMC Article
Imamura M, Komoto I, Taki Y
Surg Today 2023 Dec;53(12):1325-1334. Epub 2022 Dec 7 doi: 10.1007/s00595-022-02627-z. PMID: 36473964Free PMC Article
Pieterman CRC, Valk GD
Clin Endocrinol (Oxf) 2022 Oct;97(4):409-423. Epub 2022 Apr 1 doi: 10.1111/cen.14727. PMID: 35319130Free PMC Article
Issa GC, Ravandi F, DiNardo CD, Jabbour E, Kantarjian HM, Andreeff M
Leukemia 2021 Sep;35(9):2482-2495. Epub 2021 Jun 15 doi: 10.1038/s41375-021-01309-y. PMID: 34131281
Leng L, Zhuang K, Liu Z, Huang C, Gao Y, Chen G, Lin H, Hu Y, Wu D, Shi M, Xie W, Sun H, Shao Z, Li H, Zhang K, Mo W, Huang TY, Xue M, Yuan Z, Zhang X, Bu G, Xu H, Xu Q, Zhang J
Neuron 2018 Nov 7;100(3):551-563.e7. Epub 2018 Sep 13 doi: 10.1016/j.neuron.2018.08.031. PMID: 30220511

Recent systematic reviews

Gao Y, Li R, Wu L, Yang H, Mao J, Zhao W
Endocrine 2023 Nov;82(2):442-449. Epub 2023 Sep 5 doi: 10.1007/s12020-023-03440-5. PMID: 37668926
Bouriez D, Gronnier C, Haissaguerre M, Tabarin A, Najah H
World J Surg 2022 Nov;46(11):2666-2675. Epub 2022 Jun 29 doi: 10.1007/s00268-022-06633-7. PMID: 35767091
Nastos C, Papaconstantinou D, Kofopoulos-Lymperis E, Peppa M, Pikoulis A, Lykoudis P, Palazzo F, Patapis P, Pikoulis E
Surgery 2021 Feb;169(2):302-310. Epub 2020 Sep 30 doi: 10.1016/j.surg.2020.08.021. PMID: 33008613
Ye L, Wang W, Ospina NS, Jiang L, Christakis I, Lu J, Zhou Y, Zhu W, Cao Y, Wang S, Perrier ND, Young WF Jr, Ning G, Wang W
Clin Endocrinol (Oxf) 2017 Dec;87(6):706-716. Epub 2017 Oct 16 doi: 10.1111/cen.13480. PMID: 28940393
Stålberg P, Carling T
World J Surg 2009 Nov;33(11):2234-43. doi: 10.1007/s00268-009-9924-6. PMID: 19184636

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    Curated

    • NCCN, 2023
      NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Neuroendocrine and Adrenal Tumors, 2023

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