Multiple endocrine neoplasia

The Multiple Endocrine Neoplasia (abbreviation: MEN) is the umbrella term for several specific hereditary tumor disease, which favor a cancerous proliferation of endocrine glands and accompanied by overactivity syndromes. The Multiple Endocrine Neoplasia has an incidence of 1:50,000 in the general population.

It is divided into three different types: MEN 1, MEN 2A and MEN 2B.

MEN 1

The MEN 1 ( Wermer 's syndrome, after Paul Wermer, American Internist ( 1898-1975 ) ) is characterized by neoplasia of the parathyroid glands, pituitary and islet cells in the pancreas. The disease is inherited as an autosomal dominant trait, which means children of an affected person have a 50 percent chance to earn the gene in question and ultimately to suffer from one or more of the associated tumors.

Although each of the resulting tumors of clonal origin, that is, each consisting of a single degenerate cell has emerged, all cells of the affected patients but carry the genetic error. Therefore always expect a tumor manifestation at other locations. The manifestations of MEN 1 develop over three to four decades, the observed actual tumors depend on the time of diagnosis.

The most common manifestation of MEN- 1 syndrome is of hyperparathyroidism; up to the age of 40, the disease has come to the outbreak, the majority of gene carriers. Typical symptoms are calcium-containing kidney stones, bone changes, as well as gastrointestinal and musculoskeletal disorders. The underlying hypercalcemia, however, usually already occurs in adolescence.

The second most common manifestation are neoplasms of the islet cells in the pancreas. They occur mostly together with the hyperparathyroidism. The most common hormones that are released in increased amounts from islet cells:

Rare hormones are formed ACTH, CRH, GHRH, Calcitoninprodukte, neurotensin, peptide Gastroinhibitorisches and more.

Menin, the protein that is pathologically altered in the MEN1 syndrome, participates in the normal metabolism in development processes and DNA repair. Currently about 400 different mutations in the MEN1 gene are known.

MEN 2

The MEN 2 syndromes are characterized by medullary thyroid carcinoma and pheochromocytoma.

The reasons are activating mutations of the RET proto-oncogene. The gene is located on the long arm of chromosome 10 ( 10q11.2 ) and encodes a tyrosine kinase receptor. The disease is inherited as an autosomal dominant trait. There are several different types of mutations are known which can lead to the development of the syndrome. Especially when family increased incidence of C-cell carcinoma of the suspicion of MEN 2 is obvious.

MEN 2A

The MEN -2A syndrome was described in 1961 by JH Sipple and is therefore also known as Sipple syndrome.

The most common manifestation is the Medullary thyroid carcinoma, which usually occurs in childhood and begins with a hyperplasia of C cells that produce calcitonin.

A pheochromocytoma is about 50% before the patient. In half of the cases the tumor occurs on both sides, more than half of the patients developed after unilateral removal of the adrenal gland in 10 years a pheochromocytoma of the other side.

In 15 to 20% of patients occurs primary hyperparathyroidism, usually between the ages of 20 and 40.

The MEN -2A syndrome has the following special forms:

Also FMTC ( familial medullary thyroid carcinoma engl. )

MEN 2B

The MEN 2B syndrome is also known as Williams syndrome or Pollock Gorlin syndrome Vickers. It covers not only the Medullary thyroid carcinoma and pheochromocytoma neuromas of the mucous membranes, ganglioneuromatosis, and a marfanoid habitus ( physique similar to Marfan syndrome: slender physique, long limbs, arachnodactyly, hypermobility of the joints).

Medullary thyroid carcinoma occurs in this form in earlier and grow more aggressively than in MEN 2A. The disease sometimes occurs as early as 1 year of age with metastases and usually ends in the second or third decade of life deadly.

Characteristic are the Schleimhautneurinome that occur at the tip of the tongue, the eyelids and the entire gastrointestinal tract.

Early diagnosis and treatment

For the prognosis of patients in the course of the Medullary thyroid carcinoma is crucial. The ultimately fatal course can be prevented before the occurrence of metastases only by a thyroidectomy ( complete removal of the thyroid gland). Screening of family members of patients with MEN 2A is easily possible by means of corresponding DNA analysis if the corresponding mutation of the RET proto-oncogene of the index patient is known.

In children in whom a mutation was found with a high risk of malignancy, or a mutation that is associated with MEN 2B is performed thyroidectomy and central neck lymph node dissection immediately after diagnosis position. In certain other mutations with moderate risk of malignancy, the removal of the thyroid is recommended at least before the age of 6. Mutations low-risk surgery 6 to 12 years of age, or one-to two annual pentagastrin is recommended. This is a measurement of serum calcitonin after stimulation with pentagastrin.

In all mutations detected in the area of the RET proto-oncogene annual screening tests should be performed for the presence of a phaeochromocytoma, catecholamines and metanephrines this the be determined in the blood plasma or urine.

A hyperparathyroidism can be recognized by determining the serum calcium and parathyroid hormone in intervals of several years, with familial clustering at shorter intervals.