Multiple Endocrine Neoplasia Syndromes Flashcards
what are MEN syndromes?
a. Group of disorders that affect the endocrine system
b. MEN typically involve tumors (neoplasia) in at least 2 endocrine glands
i. Tumors can be noncancerous (benign) or cancerous (malignant)
c. Clinical features depend on the endocrine glands involved
d. Each syndrome is inherited as an autosomal dominant trait with a high degree of penetrance and variable expressivity
e. Major forms of MEN syndromes are called Type 1, Type 2 (type 2A and type 2B) and type 4
prevalence of MEN syndromes
a. MEN1—estimated to vary between 2-20 per 100,000 population
b. MEN2—less common than MEN1
i. Type 2A is the most common form
ii. Type 2B is relatively uncommon, accounting for about 5% of all cases of type 2
APUD cells
a. In terms of biological features, MEN tumors arise from the amine precursor uptake and decarboxylation (APUD) group of cellsthese constitute the diffuse system of neuroendocrine cells distributed throughout the body
i. APUD—denotes the capacity of these cells to synthesize and/or secrete biogenic amines formed through activity of the enzyme L-dopa decarboxylase
b. Inherited genetic defects affect different groups of APUD cells and lead to neoplastic development of related cell types in diverse anatomic regions
common features of APUD cell population
i. Biogenic amine synthesis
1. Amine precursor uptake
2. Amine (DOPA) decarboxylase
ii. Small polypeptide H synthesis
iii. Membrane bound neurosecretory granule
tumors associated with MEN1
i. Parathyroid adenoma—most common—95%
ii. Pancreatic endocrine tumors—50%
iii. Pituitary adenoma—40%
iv. Carcinoid tumors—30%
tumors associated with MEN2A
i. Medullary thyroid carcinoma—100%
ii. Bilateral phaechromocytoma—50%
1. Of the adrenal gland—releases catecholamines
iii. Parathyroid adenoma—10%
tumors associated with MEN2B
i. Medullary carcinoma of the thyroid—100%
ii. Neuromas—100%
1. Around the mouth area
2. Help us to distinguish type 2A and 2B
iii. Marfanoid habitus—100%
iv. Phaeochromocytoma—50%
types of tumors
- Carcinoid—slow growing type of neuroendocrine tumor
- Carcinoma—type of cancer related to epithelial cells
- Adenoma—tends to benign, of epithelial origin but associated with gland
- Neuroma—tumor within the nerve tissue
conditions associated with MEN1
a. pancreas/GI endocrine; pituitary
i. Parathyroid is involved
1. Hyperparathyroidism
2. Hypercalcemia
3. Possible Zollinger Ellison syndrome
4. Various pituitary path
a. Acromegaly
b. Cushing syndrome
c. Galactorrhea
conditions associated with MEN2A
a. pheochromocytoma, medullary thyroid cancer (mutation of RET proto-oncogene)
i. Parathyroid is involved
1. Hyperparathyroidism
2. Hypercalcemia
3. Medullary carcinoma—C cells are involved here, and they release calcitonin, so hence…
4. Increased calcitonin
5. Increased catecholamines
conditions associated with MEN2B
a. Pheochromocytoma, medullary thyroid cancer (mutation of RET proto-oncogene)
i. Mucosal neuromas result
1. Mucosal nodules
2. Marfanoid body habitus
3. Medullary carcinoma—C cells are involved here, and they release calcitonin, so hence…
4. Increased calcitonin
5. Increased catecholamines
mutation in MEN Type 1
a. Caused by mutations in the MEN1 gene—encodes a protein known as menin
i. Menin functionally acts as a tumor suppressor
1. Mutations in menin cause unregulated cell division that leads to tumor formation
what is the other name for MEN Type 1
Werner Syndrome
tumors associated with MEN Type I
i. Parathyroid
ii. Pancreas—endocrine
iii. Pituitary
carcinoid tumor and MEN1
a. Carcinoid tumors have also been reported frequently in MEN1 patients
i. Male patients appear to have a predilection for developing carcinoid tumors within the thymus
ii. Women experience bronchial carcinoids whereas men almost never do
3 means of diagnosing of MEN1
i. clinical—2 or more MEN1 associated tumors
ii. familial—patient with one MEN1 associated tumor and a first degree relative with MEN1
iii. genetic—an asymptomatic carrier of MEN1 mutation (no biochemical manifestations
parathyroid glands and MEN type 1
i. although the parathyroid glands are the most frequently involved organs (95%) and hyperparathyroidism is usually the first manifestation of the syndrome, its presence may not be detected until clinical disease of the pituitary or pancreas has brought the patient to medical attention
1. hyperparathyroidism associated with MEN1 results from hyperplasia of all 4 glands—although it might be gradual
endocrine pancreas and MEN Type 1
i. neoplastic transformation of the pancreatic islet cells is the second most common manifestation of MEN1
1. tumors that develop in the pancreas can be benign or malignant
2. most frequent manifestation of MEN1 pancreatic involvement is gastrinoma
a. approx. 1/3 of patients with gastrinoma are associated with MEN1
b. tend to be multifocal and small—hard to discover and treat
3. insulinomas are the second most common type of functional pancreatic tumor in MEN1
4. other pancreatic tumors include: glucagonomas, somatostatinomas, and vasoactive intestinal polypeptide secreting tumors (VIPomas)
first manifestation of MEN1
hyperthyroidism
second manifestation of MEN1
neoplastic transformation of the pancreatic islet cells is the second most common manifestation
pituitary gland and MEN type 1
i. pituitary tumors occur in 50% to 42% of patients with MEN1
1. most tumors are functionally active and secrete prolactin
a. symptoms of hyperprolactinemia are the third most common manifestation of MEN1
i. women: galactorrhea and amenorrhea
ii. men: impotence
third manifestation of MEN1
symptoms of hyperprolactinemia
if MEN 1 patients develop tumor secreting ACTH or Growth H, then they may present with
Cushing Syndrome or acromegaly
what do patients with MEN1 syndrome have an increased frequency of?
- Patients with MEN1 syndrome have an increased frequency of both functional and non-functional adrenal cortical hyperplasia or adenomas
