Multiple Endocrine Neoplasia

- Diverse endocrine and metabolic infringements
- Symptoms are caused by infringements of secretion of one or several hormones
- Tumors often happen malignant
- The majority of tumors has a neuroectodermal origin
- Quite often syndromes of multiple endocrine neoplasia are accompanied of dysplasia of other organs and telas
- Both sporadic and family cases of multiple endocrine neoplasia are caused by genetic defects and inherited autosomal-dominant

The historical information:

- Communication between plural endocrine infringements and plural tumors of endocrine glands has been noticed by pathologists in the end of the last century. However modern representations about syndromes of multiple endocrine neoplasia have started to be formed in 50th years XX of a century. First Wermer has found out in several patients a combination of a hyperplasia of epithelial body, tumors of a hypophysis and tumors from insular cells and has suggested to name this syndrome plural endocrine adenomatosis (the modern name - multiple endocrine neoplasia type 1). A little bit later J. H. Sipple has described a syndrome including a medullar cancer of a thyroid gland and chromaffinoma. Today this syndrome can be named multiple endocrine neoplasia type 2a. Then R. N. Schimke has allocated a version of this syndrome, shown plural neuroma and other hereditary infringements (multiple endocrine neoplasia type 2b).

- Some hereditary syndromes, traditionally considered independent diseases, can be components of syndromes of multiple endocrine neoplasia. For example, the some endocrinologists consider Zollinger-Ellison syndrome as a component of multiple endocrine neoplasia type 1.

Genetics:

- All syndromes of multiple endocrine neoplasia are inherited autosomal-dominant and are characterized with high penetrance. In half of cases multiple endocrine neoplasia arises sporadically, i.e. is caused by again appeared mutation in sexual or somatic cells. The risk of disease at the child of the patient with sporadic multiple endocrine neoplasia makes 50 %. In families with multiple endocrine neoplasia the risk exceeds 75 %. Genealogic, cytogenetic and molecular-genetic researches have revealed the mutations underlying known types multiple endocrine neoplasia. These mutations can be found out by ПЦР with the subsequent hybridization about a site-specific oligonucleotides and to calculate individual and family risk of multiple endocrine neoplasia.

- Hypotheses. Tumors, characteristic for syndromes of multiple endocrine neoplasia, occur from cells of system APUD. According to the theory Pearse (1966), all cells of system APUD are derivatives of cells neuroectoderm (a nervous crest). Assume, that syndromes of multiple endocrine neoplasia are caused by mutations in cells of a nervous crest. These mutations are inherited by cells of endocrine glands and other cells of system APUD and lead to their tumoral transformation. In favour of this hypothesis existence of the so-called mixed types МЭН including hyperplasia of single cells of system APUD or tumours from such cells testifies. To mixed types of multiple endocrine neoplasia carry, for example, neurofibromatosis with attributes of multiple endocrine neoplasia types 1, 2а and 2b.

Against this hypothesis shows that fact, that at syndromes of multiple endocrine neoplasia quite often there are the new growths having an endodermal or a mesenchymal origin. It is not excluded, that the mutation causes transformation of cells only in one endocrine gland, and accompanying infringements have secondary character and are caused by hypersecretion of a hormone by cells of a primary tumour. It is known, for example, that at of multiple endocrine neoplasia type 1 hypersecretion of insulin by cells insulinoma causes hyperplasia of adenohypophysis.