Multiple Endocrine Neoplasia Flashcards
MEN usually involves tumors (neoplasia) in how many endocrine glands?
Two glands
What kind of inheritance are MEN?
What is the degree of penetrance and variable expressivity?
Autosomal dominant.
High degree of penetrance and variable expressivity.
Prevalence of MEN 1?
Estimated to vary form 2-20 per 100K in MEN 1.
What is the prevalence of MEN 2? (MEN type 2A and type 2B)
MEN 2 is less prevalent than MEN 1.
Type 2A is most common form.
2B is relatively uncommon, accounting for approx 5% of type 2.
MEN tumors arise from which group of cells?
APUD cells
Amine precursor uptake and decarboxylation cells
Which enzyme gives APUD cells the capacity to synthesize and/or secrete biogenic amines?
L-dopa decarboxylase
What tumors are associated with MEN 1 and what are their percentages? (4)
PTH adenoma 95%
Pituitary adenoma 40%
Carcinoid tumors 30%
Pancreatic endocrine tumors 50%
What tumors are associated with MEN2A and what are their percentages? (3)
PTH adenomas 10%
Thyroid carcinoma 100%
BL pheochromocytoma 50%
What tumors are associated with MEN2B and what are the percentages? (4)
Pheochromocytoma 50%
Neuromas 100%
Thyroid carcinoma 100%
Marfanoid habitus 100%
What gene is mutated in MEN 1 (AKA Wermer syndrome) leading to excess of which protein? What is its function?
MEN 1 gene that encodes menin, which is a tumor suppressor.
Where are the tumors located in a patient with Wermer syndrome?
PTG
Pancreas
Pituitary
Carcinoid tumors
Where do men and women experience carcinoid tumors in MEN 1?
Men have tumors appear to get carcinoid tumors in the thymus.
Women get bronchial carcinoids.
How is MEN 1 (Wermer’s) diagnosed:
Clinically
Familially
Genetically
Clinical: 2 or more MEN 1 associated tumors.
Familial: pt with 1 MEN 1 associated tumor and a first-degree relative with MEN 1.
Genetic: an asymptomatic carrier of MEN 1 mutation.
What are the most frequently involved organs in MEN 1?
What is the first manifestation of MEN 1 and when is it detected?
PTG.
Hyperparathyroidism is first manifestation, but it is not detected until clinical dz of pituitary or pancreas has garnered medical attn.
What is the second most common manifestation of MEN 1?
Neoplasm of the pancreatic islet cells.
What disease processes are the most common manifestation of the pancreas in MEN 1?
Gastrinoma in most frequent.
Insulinomas are second.
(Can have glucagonomas, somatostatinomas and VIPomas)
What other dz can cause increased gastrin secretion?
ZE syndrome
What do pituitary tumors secrete in MEN 1? What can it lead to?
What is another, less common, secretion of these tumors?
Prolactin —> hyperprolactinemia (trouble lactating and missing periods in women and impotence in men).
ACTH or GH —> cushing’s or acromegaly.
What is the treatment for MEN 1?
Surgical resection of the excess PTH tissue.
Surgical resection of pituitary adenomas or pharmacological management.
Subtotal pancreatectomy - removing as many multi focal tumors as possible.
MEN 2 is caused by a mutation in what gene? What does the protein it codes for effect?
Mutated RET proto-oncogene.
RET codes for an RTK the phosphorylates and activates enzymes important for cellular development.
What is the most common sign of MEN 2?
Transformation of parafollicular cells (C cells which produce calcitonin) leading to medullary thyroid carcinoma (MTC).
What are the mortality rates for pts with MEN 2A vs. MEN 2B?
Overall MEN 2B is more severe —> avg age of death is 30.
MEN 2A has avg age of 60.
What neoplasticism transformations does MEN 2A consist of?
PTG
Thyroid parafollicular C cells
Adrenal medulla
What is the progression of parafollicular cells in pts w/ MEN 2A?
C cell hyperplasia —> modular hyperplasia —> malignant degeneration over time.
