Multiple Endocrine Neoplasia (MEN)

Question 1

What is is definition of Multiple Endocrine Neoplasia (MEN)?

Answer 1

• The occurrence of tumors involving > 2 endocrine glands in a single patient
• Two major forms: MEN1, MEN2
• Inherited autosomal dominant or sporadically

Question 2

What are the various tumors/findings of MEN? (6)

Answer 2

• Parathyroid Adenomas
• Pheochromocytomas
• Enteropancreatic Tumors
• Pituitary Adenomas
• Medullary Thyroid Cancer
• Marfanoid Habitus

Question 3

​What are the genetic mutations in……

• MEN1
• MEN2A
• MEN2B
• Medullary Thyroid Cancer
• MEN4

Answer 3

• MEN1
  
  • 11q13
• MEN2A
  
  • 10cen-10q11.2
• MEN2B
  
  • 10cen-10q11.2
• Medullary Thyroid Cancer
  
  • 10cen-10q11.2
• MEN4
  
  • 12p14

Question 4

What is the tumor distribution of MEN1?

Answer 4

• Parathyroid adenoma (>90%)
• Pituitary adenoma (30-40%)
• Enteropancreatic tumors (30-70%)

Question 5

What is the tumor distrubtion of MEN2A?

Answer 5

• Medullary thyroid cancer (>90%)
• Pheochromocytoma (40-50%)
• Parathyroid hyperplasia (10-20%)

Question 6

What is the tumor distrubtion of MEN2B?

Answer 6

• Medullary thyroid cancer (>90%)
• Pheochromocytoma (40-50%)
• Mucosal Neuromas; Marfanoid Habitus

Question 7

What is the clinical diagnosis of MEN1?

Answer 7

Patient with > 2 MEN1 associated tumors
May not necessarily have a germline mutation

Question 8

What is the familial diagnosis of MEN1?

Answer 8

• Patient with:
  
  • **1 MEN1 associated tumor AND **
  • 1st degree relative w/ MEN1
• May have variable presentations

Question 9

What is the genetic diagnosis of MEN1?

Answer 9

Person who has an MEN1 mutation but does not have clinical or biochemical manifestations of MEN1 (mutant carrier)

Question 10

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

Answer 10

Somatic Mutation

Question 11

Most MEN1 germline mutations are ________.

Answer 11

Inactivating

Question 12

What screening is done for MEN1 when index patient has a germline mutation?

Answer 12

• Identify family members w/ germline mutation
  
  • Testing for tumor surveillance
• Identify 1st degree family members w/o the mutation
  
  • Alleviate them from further testing

Question 13

What screening is done for MEN1 when index patient does not have a germline mutation?

Answer 13

• 1st degree family members need to be identified by abnormal chemistries & imaging test
• Serum Ca2+ & PTH, gastrin, fasting glucose & insulin, prolactin & IGF-1, pancreas imaging

Question 14

All individuals offered MEN1 mutation testing should be provided w/ ____________ before testing.

Answer 14

Genetic Counseling

Question 15

Genetics & Inheritance of MEN2?

Answer 15

• Autosomal dominant
• Germline Mutations in the RET proto-oncogene
• RET = REarranged during Transfection
• Subtypes: MEN2A, MEN2B, Familial MTC

Question 16

The statement:

“Genotype helps predict phenotype & guides management”

is true for which MEN?

A. MEN1

B. MEN2

C. MEN4

Answer 16

MEN2

• Allows the clinician to better understand the risks that the index patient will have for associated diseases (pheochromocytoma)
• Allows for greater understanding of management of affected family members (prophylactic thyroidectomy)