Multiple Endocrine Neoplasia Type 2
by Joy Yerman
Multiple endocrine neoplasia type II (MEN-II) is an autosomal dominant disorder.
Characteristic features of MEN-II include medullary thyroid carcinoma (MTC),
C-cell hyperplasia (CCH) in about 95% of affected individuals and pheochromocytoma
in 50% (Neuman et al. 1149). MTC is marked by an overproduction of calcitonin,
a hormone which acts to lower the concentration of calcium in the blood.
Hyperplasia is an increase in the cell numbers in the para-thyroid gland.
Any of the endocrine glands can be affected; these glands are important
because they secrete the appropriate amount of hormones into the body. MEN-II
is considered a cancer because when an endocrine gland becomes enlarged
by excessive stimulation, the hyperplasic undergo a transformation and begin
uncontrolled multiplication of abnormal cells (Potts 2026). Also, continued
hyperstimulation causes benign endocrine neoplasms to undergo change and
become a malignant neoplasm or carcinoma. A carcinoma is capable of invading
adjacent structures transferring to the organs (Potts 2026).
Many times the symptoms go undiagnosed due to the fact that they are very
mild. Also, many people who experience thyroid problems don't realize that
it could be something much more serious. This was the situation for a case
study where the individual experienced bouts of high blood pressure, headaches,
and blurred vision. She was later found to have a small tumor in one adrenal
gland. The tumor was removed and the symptoms disappeared. The individual's
brother and sister also had thyroid problems. Their father died ofliver
cancer, but his adrenal and thyroid glands were also affected. Therefore,
he was never diagnosed with MEN-II because the cancer was found too late
and had already spread to his liver. A family history is taken and it is
concluded that the tumors are part of MEN-II. An individual in this family
affected with MEN-II has a 80% chance of passing it on to his or her children.
This is the reason that genetic testing and clinical screening are so very
important. The problem is that unless a person is diagnosed with MEN-II,
he is unaware of the precautions he should undergo so that future generations
in the family can avoid the sometimes deadly ramifications of MEN-II. When
MEN-II is found in a family, the members can be tested and monitored more
closely. In cases where MEN-II in discovered early, the tumor present can
be removed surgically and this is often curative.
The question now remains whether genetic testing, screening tests, or simple
blood and urine tests are more reliable and cost efficient. Until recently
the answer seemed to be inquires into a family history of cancer and /or
urine and blood tests, but now evidence shows that genetic marker tests
are best. Current studies identified germline mutations in the RET proto-oncogene
on chromosome 10 in patients with MEN-II (Mulligan 459). The mutations exist
on codons in exons 10,11, or 16. These mutations were studied in the members
of 10 families whether they were affected or unaffected with MEN-II. The
results of the study indicated germline mutations within the RET proto-oncogene
in 8 of the 10 families. In these 8 families, 27 indivi-duals, 19 of whom
were known to have negative clinical screening tests and 8 of unknown phenotype,
were genetically screened for RET mutations (Neuman et al 1150). Of these
27, 23 did not have RET mutations and negative biochemical screening results,
three were found to have RET mutations, but had negative biochemical screening,
and one individual had a germline RET mutation and subclinical MTC and pheo-chromocytoma
(Neuman et al 1150). The two remaining families who were originally diagnosed
with MEN-II years ago, were found to have the closely related syndrome,
In this study, 10 families were previously diagnosed with MEN II and it
was confirmed that 8 families had a germline mutation of the RET proto-oncogene.
These mutations were present in all of the individuals affected, segregating
from affected parents to affected offspring. This information supports the
theory that MEN-II is genetic. Also, there is evidence that this disease
has only an 80% penetrance because not all of the offspring whose parents
have MEN-II will also have the cancerous disease. In contrast, none of the
relatives had positive genetic tests. Four indivduals were previously unknown
to have the disease were found to carry RET mutations. Carrier status can
be determined in more than 95% of MEN-II families in which RET mutations
can be identified (Neuman et al 1150). Therefore, genetic marker test is
more accurate and rids the burden and cost of rescreening noncarrier individuals
In summary, anyone who is suspected to have multiple endocrine neoplasia
type II should be screened for a mutation of the RET proto-oncogene. When
a mutation is found in a individual, it is important for relatives to undergo
genetic testing. This helps to keep this dangerous cancer under control
by early diagnoses fo future generations.
Mulligan LM, Kwok JBJ, Healey CS, et al. Germline Mutations of the RET Proto-oncogene
in Multiple Endocrine Type 2A. Nature. 1993; 363: 458-460.
Neuman HPH, Eng C, Mulligan LM, et al. Consequences of Direct Genetic Testing
for Germline Mutations in the Clinical Management of the Families with Multiple
Endocrine Neoplasia, Tyoe II. Journal of American Medical Association. 1995,
October 11; 274: 1149-51.
Potts, John T. Medullary Carcinoma of the Thyroid and Calcitonin. Harrisons
Principles of Internal Medicine, 8th Ed: pgs. 2026-27
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