Multiple endocrine neoplasia
| Classification according to ICD-10 | |
|---|---|
| D44 | New formation of uncertain or unknown behavior of the endocrine glands |
| D44.8 | Involvement of multiple endocrine glands Multiple endocrine adenomatosis |
| ICD-10 online (WHO version 2019) | |
Multiple endocrine neoplasia (abbreviation: MEN ) is the umbrella term for various specific hereditary tumor diseases that promote cancerous overgrowth of endocrine glands and are associated with hyperfunction syndromes. Multiple endocrine neoplasia has an incidence of 1 in 50,000 in the population .
It is divided into three different types: MEN 1, MEN 2A and MEN 2B.
MEN 1
MEN 1 ( Wermer syndrome , according to Paul Wermer , American internist (1898–1975)) is characterized by neoplasia of the parathyroid glands , the pituitary gland and the islet cells of the pancreas . The disease is inherited in an autosomal dominant manner, which means that children of an affected person have a 50 percent chance of acquiring the gene in question and ultimately developing one or more of the associated tumors.
Although each and every one of the tumors that develop is of clonal origin, that is to say, each of them emerged from a single degenerate cell, all cells of the affected patient carry the genetic defect. Therefore, a tumor manifestation at other locations is always to be expected. The manifestations of MEN 1 develop over three to four decades, the actual tumors detected depend on the time of diagnosis.
The most common manifestation of MEN-1 syndrome is hyperparathyroidism ; By the age of 40, the majority of gene carriers have the disease. Typical symptoms are calcium-containing kidney stones , bone changes, and gastrointestinal and muscular complaints. The underlying hypercalcemia , on the other hand, usually occurs in adolescence.
The second most common manifestation is islet cell neoplasms in the pancreas. They usually occur together with hyperparathyroidism. The most common hormones that are increasingly released from the islet cells are:
| frequency | increased hormone produced | clinical syndrome |
|---|---|---|
| 75-85% | pancreatic polypeptide | |
| 60% | Gastrin | Zollinger-Ellison Syndrome |
| 30-35% | insulin | Insulinoma |
| 3–5% | vasoactive intestinal peptide (VIP) | Verner-Morrison Syndrome |
| 5-10% | Glucagon | Glucagonoma |
| 1-5% | Somatostatin |
Hormones formed less frequently are ACTH , CRH , GHRH , calcitonin products , neurotensin , gastro-inhibitory peptides and others.
Menin , the protein that is pathologically altered in MEN1 syndrome, takes part in development processes and DNA repair in normal metabolism . Currently about 400 different mutations are in the MEN1 - gene known.
MEN 2
The MEN-2 syndromes are characterized by medullary thyroid carcinoma and pheochromocytoma .
Activating mutations of the RET proto-oncogene are the cause . The gene is located on the long arm of chromosome 10 (10q11.2) and codes for a tyrosine kinase receptor . The disease is inherited as an autosomal dominant trait . Several different types of mutation are known that can lead to the development of the syndrome. The suspicion of MEN 2 is particularly likely when C-cell carcinomas occur in families .
MEN 2
The MEN-2 syndrome was described by JH Sipple in 1961 and is therefore also called Sipple syndrome .
The most common manifestation is medullary thyroid carcinoma, which usually occurs in childhood and begins with hyperplasia of the C cells that produce calcitonin .
A pheochromocytoma occurs in about 50% prior to the patient. In half of the cases the tumor occurs on both sides, more than half of the patients develop a pheochromocytoma on the other side within 10 years after unilateral removal of the adrenal gland .
Primary hyperparathyroidism occurs in 15 to 20% of patients , usually between the ages of 20 and 40.
The MEN-2A syndrome also has the following special forms:
- Familial medullary thyroid carcinoma
Also FMTC ( familial medullary thyroid carcinoma )
- MEN 2A with cutaneous lichen amyloidosis
- MEN 2A with Hirschsprung's disease
MEN 3
MEN-3 syndrome (formerly MEN-2B syndrome) is also known as Williams-Pollok syndrome or Gorlin-Vickers syndrome . In addition to medullary thyroid carcinoma and pheochromocytoma, it includes neurinomas of the mucous membranes, ganglioneuromatosis , and a marfanoid habit (physique similar to Marfan's syndrome : slim physique, long extremities, arachnodactyly , hyperextensibility of the joints).
Medullary thyroid carcinoma occurs earlier in this form and grows more aggressively than in MEN 2A. The disease occasionally occurs with metastases in the first year of life and usually ends fatally in the second or third decade.
Characteristic are the mucosal neuromas that occur on the tip of the tongue, the eyelids and in the entire gastrointestinal tract.
Early detection and therapy
The course of medullary thyroid cancer is decisive for the prognosis of the patient. The ultimately fatal course can only be prevented by a thyroidectomy (complete removal of the thyroid gland) before metastases occur. A screening of the family members of a patient with MEN 2A is easily possible by means of a corresponding DNA analysis if the corresponding mutation of the RET proto-oncogene of the index patient is known.
In children who have a mutation with a high risk of degeneration or a mutation associated with MEN 2B, thyroidectomy and central cervical lymph node dissection are performed immediately after diagnosis . In the case of certain other mutations with a medium risk of degeneration, removal of the thyroid is recommended at least before the age of 6. For mutations with a low risk, surgery is recommended between the ages of 6 and 12. The one to two-year pentagastrin test (determination of serum calcitonin after stimulation with pentagastrin ), which was previously recommended , is currently (2015) no longer performed because pentagastrin is no longer available.
In the case of all detected mutations in the area of the RET proto-oncogene, annual screening examinations for the presence of a pheochromocytoma should be carried out; the catecholamines and metanephrines in the blood plasma or urine are determined for this.
Hyperparathyroidism can be recognized by determining the serum calcium and parathyroid hormone at intervals of several years, or at shorter intervals if the family accumulates.
literature
- Dietel, Dudenhausen, Suttorp (ed.): Harrison's internal medicine. Berlin 2003, ISBN 3-936072-10-8 , pp. 2387-2391.
- F. Marini, A. Falchetti, F. Del Monte, S. Carbonell Sala, I. Tognarini, E. Luzi, ML Brandi: Multiple endocrine neoplasia type 2. In: Orphanet J Rare Dis. 2006 Nov 14; 1, p. 45. PMID 17105651 , PMC 1654141 (free full text)
