| ICD-10 | D44.8 |
|---|---|
| ICD-9 | 193 |
| OMIM | 171400 |
| DiseasesDB | 7984 |
| MedlinePlus | 000399 |
| eMedicine | med/1520 |
| ICD-10 | D44.8 |
|---|---|
| OMIM | 162300 |
| DiseasesDB | 7991 |
| eMedicine | med/1520 |
Multiple endocrine neoplasia type 2 is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs (e.g. thyroid, parathyroid, and adrenals), but may also occur in endocrine tissues not in a classical endocrine organ. MEN2 is itself a sub-type of MEN (multiple endocrine neoplasia).
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Classification
Before gene testing was available, the type and location of tumors determined which type of MEN2 a person had. Gene testing now allows a diagnosis before tumors or symptoms develop. A table in the multiple endocrine neoplasia article compares the various MEN syndromes. MEN2 and MEN1 are distinct conditions, despite their similar names. MEN2 includes MEN2A, MEN2B, and familial medullary thyroid cancer. The common feature among the three sub-types of MEN2 is a high propensity to develop medullary thyroid carcinoma.
Presentation
MEN2 can present with a sign or symptom related to a tumor or, in the case of multiple endocrine neoplasia type 2b, with characteristic musculoskeletal and/or lip and/or gastrointestinal findings.
Causes
The table in the multiple endocrine neoplasia article lists the genes involved in the various MEN syndromes. Most cases of MEN2 derive from a variation in the RET proto-oncogene. The protein produced by the RET gene plays an important role in the TGF-beta (transforming growth factor beta) signaling system. Because the TGF-beta system operates in numerous tissues throughout the body, variations in the RET gene can have effects in numerous tissues throughout the body. MEN2 generally results from a gain-of-function variant of a RET gene. Other diseases, such as Hirschsprung disease, result from loss-of-function variants. OMIM #164761 lists the syndromes associated with the RET gene.
Genetics
When inherited, multiple endocrine neoplasia type 2 is transmitted in an autosomal dominant pattern, which means affected people one affected parent, and possibly-affected siblings and chlidren. Some cases, however, result from spontaneous new mutations in the RET gene. These cases occur in people with no family history of the disorder. In MEN2B, for example, about half of all cases arise as spontaneous new mutations.
Differences in presentation
As noted, all types of MEN2 include medullary thyroid carcinoma. MEN2A is additionally characterized by the presence of pheochromocytoma, and parathyroid hyperplasia or tumor. MEN2B is additionally characterized by the presence of pheochromocytoma, mucocutaneous neuroma, gastrointestinal symptoms (e.g. constipation and flatulence), and muscular hypotonia. It has recently been theorized that Abraham Lincoln had MEN2B.[1]
