MEN syndrome

Question 1

Characterized by the occurrence of tumors involving 2 or more endocrine glands in a single patient

Inherited autosomal dominant or sporadically

Answer 1

MEN or multiple nodular neoplasia

Question 2

functional, PTH‐secreting benign neoplasms arising from normal parathyroid tissue that lead to high serum calcium, low serum phosphorus and a non‐ suppressed or elevated serum parathyroid hormone concentration.

Answer 2

Parathyroid adenomas

Question 3

catecholamine‐secreting tumors that arise from chromaffin cells of the adrenal medulla . Can present with hypertension, headaches, palpitations, and diaphoresis.

Answer 3

Pheochromocytoma:

Question 4

neuroendocrine tumors of intestine and pancreas; examples include: gastrinoma, insulinoma, glucagonoma, and nonfunctioning pancreatic tumors

Answer 4

Enteropancreatic tumors:

Question 5

tumors of the anterior pituitary gland. Can be nonfunctional or secrete prolactin, ACTH, growth hormone, LH/FSH, or TSH (the latter glycoprotein‐secreting tumors are rare).

Answer 5

Pituitary Adenomas:

Question 6

Neuroendocrine tumor arising from the parafollicular (C) cells of the thyroid. Can secrete calcitonin. 75% of cases are sporadic, 25% are familial.

Answer 6

Medullary Thyroid Cancer:

Question 7

⇓ upper body/lower body ratio, abnormal posterior position of mandible, ⇓ cephalic index (head width/length). No ectopic lentis* or aortic abnormalities

Answer 7

Marfanoid Habitus:

Question 8

what is the chromosomal abnormality in MEN1

Answer 8

11q13

Question 9

Seen in >90% pts wth MEN1

Answer 9

Parathyroid adenoma

Question 10

What are the three most common things we see in MEN1?

Answer 10

Parathryoid adenmoa >90%

Pituitary adenmoa in 30-40%

Entero-pancreatic tumors: 30-70%

Question 11

What is the genetic abnormality seen in MEN2A

Answer 11

Medullary thyroid cancer >90%

Question 12

What are three condicitons associated with MEN2

Answer 12

MEdullary thryoid cancer

Pheochrmocytoma

Parathyroid hyperplasia

Question 13

How do you make a CLNICAL Dx for MEN1?

Answer 13

– A patient with 2 or more MEN‐1 associated tumors :

parathryoid adenoma, pituitary adenoma, enteropancreatic tumor

Question 14

HOw do you make a FAMILIAL dx of MEN1?

Answer 14

– A patient with 1 MEN1 associated tumor and a 1st degree relative with MEN1

Question 15

How do you make a genetic dx of MEN1

Answer 15

– A person who has an MEN1 mutation but does not have a clinical or biochemical manifestations of MEN1, that is a mutant carrier

Question 16

Patients diagnosed clinically may not necessary have a

Answer 16

germline mutation.

Question 17

Family members with MEN1 may have variable presentations and not all patients with MEN1 will have a

Answer 17

defined mutation.

Question 18

Chromosome 11q13 in MEN1 role:

Answer 18

Regulated transcription, genome stability, cell division and proliferation

Question 19

Inheritance of a germline MEN1 mutation predisposes a person to develop a tumor that arises after a

Answer 19

somatic mutation

Question 20

Most MEN1 germline mutations are_________

> 10% of MEN1 germline mutations arise _____

Answer 20

inactivating

de novo

Question 21

lack of genotype/phenotype correlation

Answer 21

MEN1

Question 22

The genetic content of MEN1 cannot predict

Answer 22

phenotype

Question 23

Earliest presentation of MEN1 is usually:

Answer 23

hyperPTH secreation from parathyroid tumor

Question 24

MEN1 germline mutation testing should be offered to index patients with MEN1 and their first degree relatives including asymptomatic or those with clinical manifestations.

If the index case has a germline mutation, then identifying family members with the germline mutation will help to determine appropriate testing for tumor surveillance

Identifying 1st degree family members that do not have the germline mutation of the index case will alleviate them from further testing.

Answer 24

understand concept

Question 25

If the index patient does not have an identified germline mutation, then 1st degree family members will need to be identified by abnormal chemistries and imaging test:

Answer 25

for example serum calcium and PTH, gastrin, fasting glucose & insulin, prolactin and insulin like growth factor (IGF‐1) and pancreas imaging.

Question 26

– Medullary Thyroid Carcinoma (MTC)

– Pheochromocytoma
– Primary Hyperparathyroidism

Answer 26

MEN2

Question 27

Mutation seen in MEN2

Answer 27

Germline Mutations in the RET proto‐oncogene

– RET: REarranged during Transfection
– Subtypes MEN 2A, MEN 2B, Familial MTC

Question 28

what do typical faces look like in pts with MEN2?

Answer 28

mucosal neuromas, scalloped tongue and big lips

Question 29

Understanding the genotype in a patient with_____ or familial medullary thyroid cancer allows the clinician to better understand the risks that the index patient will have for associated diseases such as pheochromocytoma, and will allow for a greater understanding of the management of affected family members such as timing of prophylactic thyroidectomy

Answer 29

MEN2

Question 30

MEN1 and MEN2 are typically ______ diseases associated with multiple endocrine tumors

Answer 30

autosomal dominant

Question 31

Identification of mutations can aide in the identification of at risk family members and particularly in____ help understand behavior and risk of the disease.

Answer 31

MEN2