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Multiple endocrine neoplasia type 4(MEN4)

MedGen UID:
373469
Concept ID:
C1970712
Neoplastic Process
Synonym: MULTIPLE ENDOCRINE NEOPLASIA, TYPE IV
SNOMED CT: Multiple endocrine neoplasia type 4 (715907003); MEN (multiple endocrine neoplasia) 4 syndrome (715907003)
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): CDKN1B (12p13.1)
 
Monarch Initiative: MONDO:0012552
OMIM®: 610755
Orphanet: ORPHA276152

Definition

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.

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.

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. [from MedlinePlus Genetics]

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.
Carcinoma
MedGen UID:
2867
Concept ID:
C0007097
Neoplastic Process
A malignant tumor arising from epithelial cells. Carcinomas that arise from glandular epithelium are called adenocarcinomas, those that arise from squamous epithelium are called squamous cell carcinomas, and those that arise from transitional epithelium are called transitional cell carcinomas (NCI Thesaurus).
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis (anterior pituitary).
Kidney angiomyolipoma
MedGen UID:
69146
Concept ID:
C0241961
Neoplastic Process
A benign renal neoplasm composed of fat, vascular, and smooth muscle elements.
Pancreatic endocrine tumor
MedGen UID:
66883
Concept ID:
C0242363
Neoplastic Process
A neuroendocrine tumor originating in a hormone-producing cell (islet cell) of the pancreas.
Parathyroid gland adenoma
MedGen UID:
75502
Concept ID:
C0262587
Neoplastic Process
A benign tumor of the parathyroid gland that can cause hyperparathyroidism.
Hashimoto thyroiditis
MedGen UID:
151769
Concept ID:
C0677607
Disease or Syndrome
Hashimoto's disease is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. Hashimoto's disease is a form of chronic inflammation that can damage the thyroid, reducing its ability to produce hormones.\n\nOne of the first signs of Hashimoto's disease is an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing. As damage to the thyroid continues, the gland can shrink over a period of years and the goiter may eventually disappear.\n\nOther signs and symptoms resulting from an underactive thyroid can include excessive tiredness (fatigue), weight gain or difficulty losing weight, hair that is thin and dry, a slow heart rate, joint or muscle pain, and constipation. People with Hashimoto's disease may also have a pale, puffy face and feel cold even when others around them are warm. Affected women can have heavy or irregular menstrual periods and difficulty conceiving a child (impaired fertility). Difficulty concentrating and depression can also be signs of a shortage of thyroid hormones.\n\nHashimoto's disease usually appears in mid-adulthood, although it can occur earlier or later in life. Its signs and symptoms tend to develop gradually over months or years.
Hyperparathyroidism
MedGen UID:
6967
Concept ID:
C0020502
Disease or Syndrome
Excessive production of parathyroid hormone (PTH) by the parathyroid glands.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Primary hyperparathyroidism
MedGen UID:
66354
Concept ID:
C0221002
Disease or Syndrome
A type of hyperparathyroidism caused by a primary abnormality of the parathyroid glands (e.g., adenoma, carcinoma, hyperplasia). Primary hyperparathyroidism is associated with hyercalcemia.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMultiple endocrine neoplasia type 4
Follow this link to review classifications for Multiple endocrine neoplasia type 4 in Orphanet.

Professional guidelines

PubMed

Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Beckers A, Rostomyan L, Daly AF
Ann Endocrinol (Paris) 2012 Apr;73(2):62-4. Epub 2012 Apr 13 doi: 10.1016/j.ando.2012.03.028. PMID: 22503805

Recent clinical studies

Etiology

Chevalier B, Coppin L, Romanet P, Cuny T, Maïza JC, Abeillon J, Forestier J, Walter T, Gilly O, Le Bras M, Smati S, Nunes ML, Geslot A, Grunenwald S, Mouly C, Arnault G, Wagner K, Koumakis E, Cortet-Rudelli C, Merlen É, Jannin A, Espiard S, Morange I, Baudin É, Cavaille M, Tauveron I, Teissier MP, Borson-Chazot F, Mirebeau-Prunier D, Savagner F, Pasmant É, Giraud S, Vantyghem MC, Goudet P, Barlier A, Cardot-Bauters C, Odou MF
J Clin Endocrinol Metab 2024 Jun 17;109(7):e1482-e1493. doi: 10.1210/clinem/dgae055. PMID: 38288531
Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Faggiano A, Fazzalari B, Mikovic N, Russo F, Zamponi V, Mazzilli R, Guarnieri V, Piane M, Visco V, Petrucci S
Genes (Basel) 2023 Sep 10;14(9) doi: 10.3390/genes14091782. PMID: 37761922Free PMC Article
Ruggeri RM, Benevento E, De Cicco F, Grossrubatscher EM, Hasballa I, Tarsitano MG, Centello R, Isidori AM, Colao A, Pellegata NS, Faggiano A
Endocrine 2023 Dec;82(3):480-490. Epub 2023 Aug 26 doi: 10.1007/s12020-023-03497-2. PMID: 37632635
Anik A, Abaci A
Minerva Pediatr 2014 Dec;66(6):533-47. Epub 2014 Sep 22 PMID: 25243504

Diagnosis

Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Faggiano A, Fazzalari B, Mikovic N, Russo F, Zamponi V, Mazzilli R, Guarnieri V, Piane M, Visco V, Petrucci S
Genes (Basel) 2023 Sep 10;14(9) doi: 10.3390/genes14091782. PMID: 37761922Free PMC Article
Ruggeri RM, Benevento E, De Cicco F, Grossrubatscher EM, Hasballa I, Tarsitano MG, Centello R, Isidori AM, Colao A, Pellegata NS, Faggiano A
Endocrine 2023 Dec;82(3):480-490. Epub 2023 Aug 26 doi: 10.1007/s12020-023-03497-2. PMID: 37632635
Anik A, Abaci A
Minerva Pediatr 2014 Dec;66(6):533-47. Epub 2014 Sep 22 PMID: 25243504
Vasilev V, Daly AF, Petrossians P, Zacharieva S, Beckers A
Endocr Pract 2011 Jul-Aug;17 Suppl 3:41-6. doi: 10.4158/EP11064.RA. PMID: 21613050

Prognosis

Faggiano A, Fazzalari B, Mikovic N, Russo F, Zamponi V, Mazzilli R, Guarnieri V, Piane M, Visco V, Petrucci S
Genes (Basel) 2023 Sep 10;14(9) doi: 10.3390/genes14091782. PMID: 37761922Free PMC Article
Ruggeri RM, Benevento E, De Cicco F, Grossrubatscher EM, Hasballa I, Tarsitano MG, Centello R, Isidori AM, Colao A, Pellegata NS, Faggiano A
Endocrine 2023 Dec;82(3):480-490. Epub 2023 Aug 26 doi: 10.1007/s12020-023-03497-2. PMID: 37632635
Armeni E, Grossman A
Endocr Pathol 2023 Mar;34(1):57-78. Epub 2022 Nov 18 doi: 10.1007/s12022-022-09742-0. PMID: 36401106
Vasilev V, Daly AF, Zacharieva S, Beckers A
Horm Metab Res 2020 Aug;52(8):553-561. Epub 2020 Apr 16 doi: 10.1055/a-1143-5930. PMID: 32299111
Vandeva S, Daly AF, Petrossians P, Zacharieva S, Beckers A
Eur J Endocrinol 2019 Dec;181(6):R235-R254. doi: 10.1530/EJE-19-0602. PMID: 31658440

Clinical prediction guides

Chevalier B, Coppin L, Romanet P, Cuny T, Maïza JC, Abeillon J, Forestier J, Walter T, Gilly O, Le Bras M, Smati S, Nunes ML, Geslot A, Grunenwald S, Mouly C, Arnault G, Wagner K, Koumakis E, Cortet-Rudelli C, Merlen É, Jannin A, Espiard S, Morange I, Baudin É, Cavaille M, Tauveron I, Teissier MP, Borson-Chazot F, Mirebeau-Prunier D, Savagner F, Pasmant É, Giraud S, Vantyghem MC, Goudet P, Barlier A, Cardot-Bauters C, Odou MF
J Clin Endocrinol Metab 2024 Jun 17;109(7):e1482-e1493. doi: 10.1210/clinem/dgae055. PMID: 38288531
Mazarico-Altisent I, Capel I, Baena N, Bella-Cueto MR, Barcons S, Guirao X, Pareja R, Muntean A, Arsentales V, Caixàs A, Rigla M
Front Endocrinol (Lausanne) 2023;14:1244361. Epub 2023 Sep 21 doi: 10.3389/fendo.2023.1244361. PMID: 37810884Free PMC Article
Faggiano A, Fazzalari B, Mikovic N, Russo F, Zamponi V, Mazzilli R, Guarnieri V, Piane M, Visco V, Petrucci S
Genes (Basel) 2023 Sep 10;14(9) doi: 10.3390/genes14091782. PMID: 37761922Free PMC Article
Tonelli F, Giudici F, Giusti F, Marini F, Cianferotti L, Nesi G, Brandi ML
Eur J Endocrinol 2014 Aug;171(2):K7-K17. Epub 2014 May 12 doi: 10.1530/EJE-14-0080. PMID: 24819502

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