Multiple Endocrine Neoplasia Syndromes (MEN)

Question 1

what are MEN syndrome?

Answer 1

neuroendocrine tumors that can appear in multiple endocrine organs!

these syndromes are usually autosomal dominant with high penetrance and variable expressivity

Question 2

Most common MEN?

within Men type 2? what about what’s more aggressive

Answer 2

1.

2a is more common than 2B

2B is more aggressive

Question 3

How can so many various endocrine organs be affected in these syndromes?

Answer 3

common origin to these MEN tumors.

the common origin is from the machinery that we use from our body to generate peptide hormones or amine hormones.

from amine precursor, Uptake, and decarboxylation (APUD) cell

Question 4

What happens during MEN1?

Answer 4

Parathyroid adenoma (95%) --> hyperparathyroidism
Pituitary Adenoma (40%)
Pancreatic endocrine tumor (50%) --> gastronome

PPP

Question 5

MEN2 has one difference that MEN1?

What is in men2A that is not in MEN2B?

What is shared between MEN1 and MEN2A?

MEN2B only there?

Answer 5

MEN2 has medullary thyroid carcinoma, MEN1 doesn’t.

Bilateral Phaeochromocytoma in 2A, but not in 2B

Parathyroid Adenoma

Neuromas, Marfanoid Habitus

Question 6

for MEN1, what tumor is going to start in the 3 Ps?

What tumor is coming off of the pancreas for type 1?

Answer 6

Hyperparathyroidism.

Gastrinoma!

Question 7

What is Marfanoid Habitus?

Answer 7

only in MEN2B.

Question 8

Different things seeing in MEN1?

Answer 8

Hyperparathyroidism
Hypercalcemia (from above)
Possible ZE syndrome
Pituitary –> ZE, Cushing syndrome, Galactorrhea (also problems with FSH, LH, libido)

Question 9

Cushing Disease

Cushing syndrome?

Answer 9

pituitary secreting ACTH

Adrenal secreting Cortisol

Question 10

Neoplasia in the thyroid gland can lead to what pathologies?

what happens from a pheochromocytoma

Answer 10

Calcitonin

catecholamines (from pheochromocytoma)

Question 11

What is MEN type 1 also called?

What is MEN1 gene usually doing?

what is it caused by?

what happens when there’s a mutation here

Answer 11

Wermer Syndrome

MEN1 is usually a tumor suppressor!

MEN1 gene, which encodes the renin protein!

mutations in menin cause unregulated cell division leading to tumor formation.

Question 12

What are the three ways to diagnose MEN1?

Answer 12

Clinical: two or more MEN1 associated tumors.

Familial: Patient with one MEN1 associated tumor and first degree relative with MEN1

Genetic: Asymptomatic carrier of MEN1 mutation (no biochemical manifestations)

Question 13

MEN1 parathyroid tumors.. what’s going to happen?

Answer 13

hyperparathyroidism is usually the first manifestation of the syndrome.

Question 14

MEN1 and the pancreas… what’s going to happen?

second most common?

Answer 14

most frequently manifestation is involving a gastronome.

Insulinomas leading to hypoglycemia

Question 15

What kind of tumor is a gastrinoma on a pancreas?

Answer 15

Ectopic, because it doesn’t really belong there.

Question 16

ZE syndrome for MEN type 1?

Answer 16

this is a gastrinoma. you’re going to have an over secretion of gastrin so you’ll have a ton of ulcers (both stomach and duodenal)

Question 17

MEN1 on the pituitary gland?

Answer 17

most tumors are active and secrete prolactin!

leads to hyperprolactinemia, amenorrhea, impotence in men.

Question 18

why is prolactin going to inhibit FSH/LH?

Answer 18

prolactin will down regulate GnRH from the hypothalamus which will down regulate FSH/LH

Question 19

Treatment for MEN1?

Answer 19

surgical resection

Question 20

MEN2 mutation?

Answer 20

mutation of the RET protooncogene

the protein is RET (which is a receptor tyrosine kinase)

this will lead to the phosphorylation of critical components.

Question 21

MEN2 neoplastic changes with medullary thyroid carcinoma?

(this is common in both 2A and 2B

Answer 21

transformation of the parafollicular cells (or C cells) –> increasing size and amount of them –> upregulates how much Calcitonin is increased

Question 22

Pheochromocytoma and MEN2?

Answer 22

more catecholamine secretion, leading to hypertension.

Question 23

Mortality between 2A and 2B?

Answer 23

2B is more severe, reducing average life to 30.

2A = 60 years.

Question 24

MEN2A is called what?

what does it cause?

Answer 24

Simple syndrome

increased parafollicular C cells + Adrenal medulla transformation (pheochromocytoma)

Question 25

what can happen to normal tissue?

Answer 25

normal tissue can have two changes:

1)hypertrophy (change in cell size)

or

2) Hyperplasia (number of cells)

Question 26

Hyperplasia can be what types?

Answer 26

focal (only in one spot)
diffuse (only on the outside)
nodular

neoplasia is a mix of all of them.

Question 27

Cutaneous Lichen Amyloidosis is present where? why?

Answer 27

MEN2

this could be related to calcitonin levels –> causes a rash from amyloid deposition.

Question 28

MEN2B has what?

Answer 28

medullary thyroid carcinoma –> more agressive

neuroma –> affecting the tongue mostly.

Marfanoid body habitus –> patient with extremely elongated extremity (especially the arms)

elongation of the fingers (arachnodactyly)

Question 29

Congenital adrenal hyperplasia, which type is hypotensive

Answer 29

not 11.. it’ll be 21b-hydroxylase!