1. MULTIPLE ENDOCRINE
NEOPLASIA SYNDROMES
Prepared by:
Sajad Abd Al-Rudha Ali

2. What is meant by NEOPLASIA???
The term Neoplasia refers to a new,
excessive growth of cells that is not under
physiologic control, like tumors or mass
lesions. It’s Unlike cancer that implies only
malignancy tumors, Neoplasms can be
classified as either benign or malignant.

3.  Multiple endocrine neoplasia syndromes
are autosomal dominant mutations in the
genes that regulate the growth of the cells,
in which the endocrine glands develop non
cancerous (benign) or cancerous
(malignant) tumors or grow excessively
without forming tumors in at least two
endocrine glands. Almost all of the cases
are inherited and they affect an estimated 1
in 30,000 people and it affects men and
women equally.

4.  According to the difference in the characteristic signs,
symptoms and risk of specific tumors; this syndrome is
occurred in two patterns:-
Type 1 Disease (Werner’s syndrome) : People with this type of
disease have a tumor or excessive growth or activity in more
than one of the following glands:
 Parathyroid gland
 Pituitary gland
 Pancreas gland
 Thyroid gland (less often affected)
 Adrenal gland (less often affected).

5. Type 2 Disease (Sipple’s syndrome) : This is subdivided into:
Type 2A Disease: People with this type of disease have a
tumor or excessive growth or activity of two or three of the
following glands:
 Parathyroid
 Thyroid
 Adrenal gland.
Type 2B Disease: It’s developed at an early age in infants
as young as 3 months, this type is characterized by:
 Medullary Thyroid Carcinoma MTC
 Pheochromocytomas
 Growths around nerves (neuromas)
 Marfan’s syndrome.

7. Pathophysiology
Mutations in the MENIN and RET genes cause multiple
endocrine neoplasia.
 Mutations in the MENIN gene (a gene that’s located on
chromosome 11)cause multiple endocrine neoplasia type1.
This gene provides instructions for producing a protein called
MENIN . Menin acts as a tumor suppressor, which means it
normally keeps cells from growing and dividing too rapidly or
in an uncontrolled way. Although the exact function of MENIN
is unknown, it is likely involved in cell functions such as
copying and repairing DNA and regulating the activity of
other genes. If mutations inactivate both copies of the MENIN
gene, it is no longer able to control cell growth and division.
The loss of functional MENIN allows cells to divide too
frequently, leading to the formation of tumors characteristic of
multiple endocrine neoplasia type 1.

8.  Multiple endocrine neoplasia type 2 results from mutations
in the RET gene( a gene that’s located on chromosome 10).
This gene provides instructions for producing a protein that is
involved in signaling within cells. The RET protein triggers
chemical reactions that instruct cells to respond to their
environment, for example by dividing or maturing. Mutations
in the RET gene over activate the protein's signaling function,
which can trigger cell growth and division in the absence of
signals from outside the cell. This unchecked cell division can
lead to the formation of tumors in endocrine glands and other
tissues.

9.  If you inherit one defective copy of a MENIN gene from
either parent, there's a high probability of having a second
mutation in at least one dividing cell. Then, that cell no
longer possesses even one normal copy of the gene. When
both copies are defective, tumors develop.
 Both types of MEN2 are caused by mutations in the RET
gene. A mutation in only one copy of the RET gene is
enough to cause the disease.

11. Symptoms
 Its effect depends on which glands are affected. MEN1
patients will have hyperplasia or tumors of several endocrine
glands, including the parathyroids, the pancreas, and the
pituitary. The most common symptom of MEN1 is
hyperparathyroidism, which leads to elevated blood calcium
levels, kidney stones, weakened bones, and depression of the
nervous system. Usually The symptoms appear at the age 40.
 Patients with MEN2A and MEN2B will have two main
symptoms-medullary thyroid cancers (MTC) and a tumor of
the adrenal gland medulla known as pheochromocytoma.
Medullary thyroid carcinoma forms from the C-cells of the
thyroid. C-cells make the hormone calcitonin , which is
involved in regulating the calcium levels in the blood and
calcium absorption by the bones, It is a slow-growing cancer,
it can be cured in less than 50% of the cases.

12. Pheochromocytoma is usually a benign tumor that causes
excessive secretion of adrenal hormones, which, in turn,
can cause life-threatening hypertension and cardiac
arrhythmia.
 MEN2B patients are also characterized by swollen lips;
tumors of the mucous membranes of the eye, mouth,
tongue, and nasal cavity; enlarged colon; and skeletal
abnormalities. Symptoms develop early in life, often under
five years of age.

13. tumors of the mucous membranes of the tongue

14. There are other symptoms that vary from person to another like:
 Abdominal pain
 Anxiety
 Black, tarry stools
 Bloated feeling after meals
 Burning, aching, or hunger discomfort in the upper abdomen or lower chest that is relieved by
antacids, milk, or food
 Decreased sexual interest, loss of body or facial hair (in men)
 Fatigue
 Headache
 Lack of menstrual periods, infertility, or failure to produce breast milk (in women)
 Loss of appetite
 Loss of coordination
 Loss of underarm or pubic hair
 Mental changes or confusion
 Muscle pain
 Nausea and vomiting
 Sensitivity to the cold
 Unintentional weight loss
 Vision problems
 weakness

15. Diagnosis
 When checking for a misdiagnosis of MEN or confirming a
diagnosis of MEN it’s useful to consider what other medical
conditions might be possible misdiagnosed or other
alternative conditions relevant to diagnose.
 Diagnose is based on clinical features and testing for elevated
hormone levels.
 The occurrence of one endocrine condition does not
immediately lead to a suspicion of MEN syndromes.
Diagnoses is based on the occurrence of one or more
endocrine conditions and a family history of MEN1 or MEN2.
 Magnetic resonance imaging or computed tomography scan of
the cranial nerves, also in the abdomen may show pancreatic
tumor.

16.  Genetic tests are done to people who have one of the
tumors associated with multiple endocrine neoplasia and
in family members of people already diagnosed with one of
the syndromes.
 Screening of the family members is particularly important
because about half of the children of people with a
multiple endocrine neoplasia syndrome inherit the disease.
 Diagnostic tests must be used to carefully evaluate each
affected endocrine gland. For example, radioimmunoassay
showing increased levels of gastrin in patients with peptic
ulceration and Zollinger-Ellison syndrome suggests the
need for follow-up studies for MEN I because 50% of
patients with Zollinger-Ellison syndrome have MEN.
 Also you can diagnose MEN by testing serum glucagon,
insulin, and parathyroid hormone

17. Treatment
 Treatment depends upon the type of tumor that is present( its
location, staging, and any hormone abnormality that may
present)
 No cure is known for any of the multiple endocrine neoplasia
syndromes. Doctors treat the changes in each gland
individually. A tumor is treated by removing it surgically when
possible, Hormone replacement therapy is given when glands
are removed or do not produce enough hormones.
 If removal is not possible (and before removal), doctors tend
to give drugs to correct the hormone imbalance caused by
gland over activity. For example: Bromocriptine may be used
instead of surgery for pituitary tumors that release the
hormone prolactin. Other medicine such as omperazole to
reduce the risk of ulcers, diazoxide for elevating blood glucose
and octreotide for the inhibition f growth hormones.

18. Thank you