Multiple endocrine neoplasia
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| Multiple endocrine neoplasia | |
| ICD-10 | D44.8 |
|---|---|
| MeSH | D009377 |
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Overview
Multiple endocrine neoplasia (MEN) (or "multiple endocrine adenomas", or "multiple endocrine adenomatosis" -- "MEA") consists of three syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. The presence of any one tumor type does not automatically have a patient labelled as MEN, but a search of the other at-risk areas is usually undertaken, especially when there are suggestive clinical signs.
MEN syndromes are inherited as autosomal dominant disorders. Medullary carcinoma of the thyroid may occur as an autosomal dominant in the absence of other features.
Comparison
| Feature | MEN 1 | MEN 2 | ||
|---|---|---|---|---|
| MEN 2A | MEN 2B | FMTC | ||
| Eponym | Wermer syndrome | Sipple syndrome | (see below) | (none) |
| OMIM | Template:OMIM4 | Template:OMIM4 | Template:OMIM4 | Template:OMIM4 |
| Pancreatic tumors | insulinoma, gastrinoma | - | - | - |
| Pituitary adenoma | Yes | - | - | - |
| Parathyroid hyperplasia | Yes | Yes | - | - |
| Medullary thyroid carcinoma | - | Yes | 100% | 100% |
| Pheochromocytoma | - | Yes | 50% | - |
| Marfanoid body habitus | - | - | 80% | - |
| Multiple Mucosal Neuromata | - | - | >95% | - |
| Spontaneous mutation rate | 50% | |||
| Gene(s) | MEN1 (Template:OMIM4) | RET (Template:OMIM4) | RET (Template:OMIM4) | RET (Template:OMIM4), NTRK1 (Template:OMIM4) |
| Approx. prevalence | 1 in 1,000,000 | |||
| Initial description (year) | 1954[1] | 1961[2] | 1965 | |
(Blanks indicate that data are not yet available.)
MEN 2B was known as MEN 3 for a short time in the 1970s, but that term is no longer used. Although a variety of eponyms have been proposed for MEN2B (e.g. Williams-Pollock syndrome, Gorlin-Vickers syndrome, and Wagenmann-Froboese syndrome), none ever gained suffiicient traction to merit continued use and, indeed, are all but abandoned in the medical literature. Another early report was Schimke et al in 1968.[3]
OMIM also includes a fourth form of multiple endocrine neoplasia ("MEN4"), associated with CDKN1B.[4] The presentation is believed to overlap that of MEN1 and MEN2.[5]
MEN type 1
Type 1 is also known as Wermer's syndrome after Dr Paul Wermer, who described it in 1954:[6]
- Parathyroid hyperplasia/tumour causing hyperparathyroidism.
- Pancreatic islet cell tumours causing hypoglycaemia (insulinoma) and Zollinger-Ellison syndrome (gastrinoma).
- Pituitary adenoma which may cause pituitary hormone excess.
The causative mutation is in the MEN1 gene at 11q13 which encodes a nuclear protein called menin that is believed to act as a tumor suppressor. Most cases of multiple endocrine neoplasia type 1 are inherited in an autosomal dominant pattern.
MEN type 2
MEN type 2/type 2a
MEN syndrome types 2 and 3 have their basis in molecular genetics. Individuals can be tested for this genetic disorder reliably even when asymptomatic. The mutation is in the RET proto-oncogene. Most cases of multiple endocrine neoplasia types 2 and 3 are inherited in an autosomal dominant pattern.
Type 2 is also known as Sipple syndrome (after the American Dr John H. Sipple, who described it in 1961)[7] and used to be called type 2A:
- Medullary carcinoma of the thyroid which is associated with increased calcitonin secretion. A test for elevated calcitonin should be done after pentagastrin injection and/or calcium infusion, to ensure that all affected patients are detected.
- Pheochromocytoma
- Parathyroid hyperplasia/tumour causing hyperparathyroidism.
MEN type 3/type 2b
This syndrome has no eponym; it was described by Schimke et al in 1968.[8] Originally thought to be a third MEN, then considered a variant of II (especially after linkage to RET was confirmed), it is now considered its own syndrome.
- Pheochromocytoma
- Medullary carcinoma of thyroid which is associated with increased calcitonin secretion. A test for elevated calcitonin should be done after pentagastrin injection and/or calcium infusion, to ensure that all affected patients are detected.
- Mucosal neuromas which are usually situated in the gastrointestinal tract.
- Marfanoid habitus
References
- ↑ Wermer P (1954). "Genetic aspects of adenomatosis of endocrine glands". Am. J. Med. 16 (3): 363–71. PMID 13138607.
- ↑ Sipple JH (1961). "The association of pheochromocytoma with carcinoma of the thyroid gland". Am. J. Med. 31: 163–6.
- ↑ Schimke RN, Hartmann WH, Prout TE, Rimoin DL (1968). "Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas. A possible regulatory defect in the differentiation of chromaffin tissue". N. Engl. J. Med. 279 (1): 1–7. PMID 4968712.
- ↑ Online Mendelian Inheritance in Man (OMIM) MULTIPLE ENDOCRINE NEOPLASIA, TYPE IV; MEN4 -610755
- ↑ Pellegata NS, Quintanilla-Martinez L, Siggelkow H; et al. (2006). "Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans". Proc. Natl. Acad. Sci. U.S.A. 103 (42): 15558–63. doi:10.1073/pnas.0603877103. PMC 1622862. PMID 17030811. Unknown parameter
|month=ignored (help) - ↑ Wermer P. Genetic aspect of adenomatosis of endocrine glands. Am J Med 1954;16:363-371. PMID 13138607.
- ↑ Sipple JH. The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med 1961;31:163-166.
- ↑ Schimke RN, Hartmann WH, Prout TE, Rimoin DL. Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas. A possible regulatory defect in the differentiation of chromaffin tissue. N Engl J Med 1968;279:1-7. PMID 4968712
External links
- Endocrine and Metabolic Diseases Information Service
- The Association for Multiple Endocrine Neoplasia Disorders (AMEND)
- Multiple Endocrine Neoplasia type 2 (MEN2 RET database)
Template:Endocrine gland neoplasia
Template:Tumor morphology Template:SIB
da:Multipel endokrin neoplasi de:Multiple endokrine Neoplasie it:Neoplasie multiendocrine sv:Multipla hormonella tumörer