Multiple Endocrine Neoplasias

Question 1

Multiple endocrine neoplasia syndromes typically involve Neoplasias of at least ______ kinds of _______ glands

Answer 1

Two kinds of endocrine glands

Question 2

MEN syndromes are typically autosomal _______ with a ____ degree of penetrance and _______ expressivity

Answer 2

Autosomal dominant with high degree of penetrance and variable expressivity

Question 3

Most common type of MEN

Answer 3

MEN 1

MEN 2B is least common

Question 4

MEN tumors arise from what cell type

Answer 4

Amine precursor uptake and decarboxylatino (APUD) group of cells

Question 5

Role of APUD cells

Answer 5

Constitute the diffuse system of neuro endocrine cells distributed throughout the body
APUD denote the capacity of these cells to synthesize and/or secrete biogenic amines formed through activity of the zone

L-dopa decaroxylase

Question 6

Enzyme that gives APUD cells their function (also what is their function)

Answer 6

L-dopa decarboxylase

APUD cells have capacity to synthesize/secrete biogenic amines

Question 7

Other functions of APUD cells

Answer 7

Biogenic amine synthesis
Amine precursor uptake
Amine decarboxylase

Small polypeptide hormone synthesis
Membrane bound neurosecretory granules

Question 8

Tumors associated with type 1 MEN

Answer 8

Pancreatic (ONLY SEEN IN TYPE 1)
Pituitary
Parathyroid
Carcinoid

Question 9

Tumors associated wth type 2A MEN

Answer 9

Thyroid
Parathyroid
Adrenal (phaeochromocytoma)

Question 10

Tumors associated with type 2B MEN

Answer 10

Neuromas *** (only seen in type 2B)

Thyroid
Phaechromocytoma

Question 11

Conditions associated with type 1 MEN

Answer 11

Hyperparathyroidism 
Hypercalcemia 
ZE syndrome 
Various pituitary path 
(Acromegaly, Cushing syndrome, galactorrhea)

Question 12

Conditions associated with type 2A MEN

Answer 12

Hyperparathyroidism 
Hypercalcemia 
Medullary carcinoma
Increased calcitonin 
Increased catecholamines

Question 13

Conditions associated with Type 2B MEN

Answer 13

Mucosal nodules ***
Marfanoid body habitus *

Medullary carcinoma
Increased calcitonin
Increased catecholamines

Question 14

Gene defect leading to type I MEN

Answer 14

Mutations in the MEN1 gene that codes for menin*

Menin usually acts as tumor suppressor

Mutation of menin leads to unregulated cell division —> tumor

Question 15

3Ps of Type 1 MEN

Answer 15

Parathyroid
Pancreas
Pituitary

Question 16

Three ways to Dx MEN1

Answer 16

Clinical: two or more MEN-1 associated tumors
Familial: patient with one MEN1 associated tumor and first degree relative with MEN1
Genetic: asymptomatic carrier of EN1 mutation (no biochemical manifestations)

Question 17

First symptom to present with type 1 MEN

Answer 17

Hyperparathyroidism

Question 18

Second most common manifestation of MEN1

Answer 18

Pancreatic islet neoplasm

Most often leads to gastrinoma

Insulomas second most common

Can also get glucagoma, somatostinoma, VIPoma

Question 19

Symptoms of hyperplasia of the pituitary

Answer 19

Occur in ~50% of MEN1

Most secrete prolactin
Leads to galactorrhea and amenorrhea in women/impotence in men

Third most common manifestation of MEN1

May develop ACTH/GH secreting humor with Cushing/acromegaly

Question 20

Treatment for MEN1 involves

Answer 20

Surgical resection of hyperplastic parathyroid tissue

Surgical resection of pituitary adenomas/management with bromocriptine for prolacitnomas/octreotide for acromegaly

Subtotal pancreatoctomy (surgical cure of associated pancreatic tumors not usually possible)

Question 21

MEN type 2 results from an activating mutation of what gene

Answer 21

RET protooncogene

RET gene codes for RTK that phosphorylates—> activates enzymes critical to cellular dev

Question 22

Most common sign of MEN2

Answer 22

Malignant transformation of parafollicular cells (c cells) resulting in medullary thyroid carcinoma

C cells normally secrete calcitonin (bone tone)