Multiple Endocrine Neoplasia - Rose

Question 1

Name five groups of tumors that can be seen in Multiple Endocrine Neoplasia.

Answer 1

• Parathyroid adenomas
  
  • ​PTH-secreting tumors of parathyroid cells
• Pheochromocytomas
  
  • Catecholamine-secreting tumors of chromaffin cells
• Enteropancreatic tumors
  
  • ​Gastrinoma, insulinoma, glucagonoma, or non-secretory
• Pituitary Adenomas
  
  • ​Can secrete prolactin, ACTH, GH, LH/FSH, or TSH, or nonfunctional
• Medullary Thyroid Cancer
  
  • From C cells. Can secrete calcitonin.

Question 2

What is Marfanoid Habitus?

Answer 2

A constellation of symptoms resembling those of Marfan Synrome. Can be seen in MEN.

• Decreased upper body : lower body ratio
• Abnormal position of mandible
• Decreased cephalic index (head witdh/length)
• Unlike Marfan, no ectopic lens or aortic abnormalities

Question 3

How can MEN1 be diagnosed:

1. Clinically?
2. Familially?
3. Genetically?

Answer 3

1. A pt with 2+ MEN1 associated tumors
2. A pt with 1 MEN1 associated tumor and a 1^st degree relative with MEN1
3. A person with an MEN1 mutation despite have no clinical or biochemical manifestations of the disease. Is a carrier.

Question 4

Do all patients with MEN1 have a defined mutation?

Answer 4

No. Patients diagnosed clinically may not necessarily have a germline mutation.

Question 5

What chromosomal abnormalitiy results in MEN1?

What is the mutated gene’s normal function?

Answer 5

11q13

Regulates transcription, genome stability, cell division and proliferation

Question 6

1. Are most MEN1 germline mutations activating or inactivating?
2. Does inheritance of the mutation guarantee tumors?

Answer 6

1. Inactivating
2. No. Presentation between patients varies widely. Inheritance of a germline MEN1 mutation predisposes a person to developing a tumor that arises after a somatic mutation (two-hit hypothesis)

Question 7

What three glands most often develop neoplasms in MEN1?

Answer 7

In one study:

• Parathyroid (95%)
• Pancreas (40%)
  
  • Gastrinoma most common
  • Insulinoma second most common
  • Others less common
• Pituitary (30%)
  
  • Prolactin most common
  • GH second most common
  • Others less common
• ~41% of pts had 2 of these affected. ~12% had all three.

Question 8

What is the typical age of onset for MEN1?

Answer 8

~20-40 years old has the greatest incidence

Question 9

1. If the index patient has a germline MEN1 mutation, what testing for MEN1 should be done for that patient’s (first degree) relatives?
2. If the index patient does not have a germline MEN1 mutation, what testing for MEN1 should be done for that patient’s relatives

Answer 9

1. Test for the germline mutation. If not present, that relative will be alleviated from further testing
2. Not as simple. Family members must be identified by abnormal chemistries and imaging tests.
   
   • serum calcium & PTH
   • gastrin
   • fasting glucose & insulin
   • prolactin & IGF-1
   • pancreas imaging

The point: Identifying a germline mutation in the index pt allows for greater ease in the screening of 1st degree relatives?

Question 10

What should always be provided to patients that have been offered an MEN1 mutation testing?

Answer 10

Genetic counselling before the test!

This was stressed heavily!

[For potential personal/family anxiety? Maybe. But probably for potential health insurance consequences… screw those guys.]

Question 11

How are MEN1 and MEN2 typically inherited?

What is the other way the disease is received?

Answer 11

Autosomal dominant for both, although:

A significant number of cases occur sporadically

Question 12

What are the three most common tumors in MEN2?

Answer 12

• Medullary Thyroid Carcinoma (MTC)
• Pheochromocytoma
• Primary Hyperparathyroidism
  
  • (Lecture seems to indiate that it’s typically hyperplasia, not adenoma)

Question 13

Mutations in what gene causes MEN2? Where is this gene located?

What subtypes are there?

Answer 13

• RET proto-oncogene, 10cen-10q11.2
  
  • “REarranged during Transfection”
  • 10cen-10q11.2 also seen in medullary thyroid cancer only
• Subtypes:
  
  • MEN 2A
  • MEN 2B (occasionally called MEN3)
  • Familial MTC (Medullary Thyroid Cancer only)

Question 14

What anatomical abnormalities does MEN2B present with?

Answer 14

• Marfanoid Habitus
• Abnormal facies including enlarged lips
• Mucosal neuromas on the tongue
  
  • Gives the edge of the tongue a serrated appearance

Question 15

Why is establishing the specific genotype/mutation of an MEN2 patient so important?

Why is this not as important for MEN1 patients?

Answer 15

• The specific mutation predicts the phenotype and guides management for both the patient and affected family members
  
  • Better understanding of the risks for specific associated diseases (e.g. pheochromocytoma)
  • Greater understanding of the management and timing of periodic screening and prophylactic care in the pt and affected family
• Unlike MEN2, genotype and phenotype are not closely related in MEN1

Question 16

What mutation causes MEN4?

Answer 16

12p14

Question 17

Name the type of MEN that most commonly corresponds to the following:

1. Medullary Thyroid Cancers
2. Enteropancreatic Cancers
3. Pheochromocytoma
4. Reproductive Organ Tumors
5. Mucosal Neuromas

[Likely high-yield!]

Answer 17

1. MEN2 (A, B, and famillial MTC subtypes)
2. MEN1
3. MEN2 (A & B)
4. MEN4
5. MEN2B