Multiple Endocrine Neoplasia - Rose Flashcards Preview

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Flashcards in Multiple Endocrine Neoplasia - Rose Deck (17):
1

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

  • 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.

2

What is Marfanoid Habitus?

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

 

3

How can MEN1 be diagnosed:

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

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

4

Do all patients with MEN1 have a defined mutation?

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

5

What chromosomal abnormalitiy results in MEN1?

What is the mutated gene's normal function?

11q13

Regulates transcription, genome stability, cell division and proliferation

6

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

  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)

7

What three glands most often develop neoplasms in MEN1?

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.

8

What is the typical age of onset for MEN1?

~20-40 years old has the greatest incidence

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

  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?

10

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

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.]

11

How are MEN1 and MEN2 typically inherited?

What is the other way the disease is received?

Autosomal dominant for both, although:

A significant number of cases occur sporadically

 

12

What are the three most common tumors in MEN2?

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

13

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

What subtypes are there?

  • 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)

14

What anatomical abnormalities does MEN2B present with?

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

15

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

Why is this not as important for MEN1 patients?

  • 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

16

What mutation causes MEN4?

 

12p14

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!]

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

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