- The term multiple endocrine neoplasia (MEN) encompasses several
distinct syndromes
- Each features tumours of endocrine glands, each with its own
characteristic pattern.
- In some cases, the tumors are malignant, in others, benign.
- Benign or malignant tumors of non-endocrine tissues occur as
components of some of these syndromes.
MEN 1 gene
- The MEN1 gene consists of ten exons, spanning about 10 kb
- It encodes a 610 amino acid protein named menin
- The first exon and the last part of exon10 are not translated
- A main transcript of 2.8 kb has been described in a large variety of
human tissues
- MEN1 follows Knudson’s “two-hit” model for tumour suppressor gene
carcinogenesis
- The first hit is a heterozygous MEN1 germ line mutation, inherited
from one parent
- The second hit is a MEN1 somatic mutation that occurs in predisposed
endocrine cells
- MEN1 gene mutations can be identified in 70-95% of MEN1 patients
- Also seen in about 20% of familial isolated
hyperparathyroidism cases
- Almost all patients are heterozygous for mutations
- 50% of patients develop signs and symptoms by 20 years of age
- More than 95% have symptoms by 40 years of age
- About one third of patients affected with MEN1 will die early from
an MEN1-related cancer or associated malignancy
- Pancreatic gastrinomas and thymic and bronchial carcinoids are the
leading cause of morbidity and mortality
MEN 1 Syndrome (Wermer's Syndrome)
| Hyperparathyroidism |
90% |
| Pancreatic Islet Cell Tumours |
60% |
| Gastrinoma |
60% |
| Insulinoma |
10% |
| Vipoma |
|
| PPoma |
|
| Glucagonoma |
|
| Pituitary Tumours |
5% |
| Prolactinoma |
|
| GH, ACTH, TSH secreting tumours |
|
| Thyroid adenoma |
|
| Adrenal adenoma |
|
| Carcinoid tumours |
|
MEN 2a Syndrome (Sipple's Syndrome)
| Medullary Thyroid Carcinoma |
100% |
| Phaeochromocytoma |
50% |
| Hyperparathyroidism |
10% |
MEN 2b Syndrome
| Medullary Thyroid Carcinoma |
100% |
| Phaeochromocytoma |
50% |
| Multiple mucosal neuromas |
100% |
| Ganglioneuromatosis of the gut |
100% |
| Marfanoid appearance |
100%> |
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