12. Multiple Endocrine Neoplasia

Question 1

What are multiple endocrine neoplasia (MEN) syndromes?

Answer 1

3 autosomal dominant disorders where at least 2 endocrine glands simultaneously undergo neoplastic transformation and become hyperfunctional. These neoplastic tumors can be benign or malignant.

Question 2

What are the clinical features of MEN?

Answer 2

depend on endocrine gland involved

Question 3

Each MEN is autosomal dominant with a _____ degree of penetrance and ________ expressivity.

Answer 3

• High degree of penetrance (if you have gene, you will express the disorder).
• Variable expressivity (the level at which a trail appears differs from person -> person)

Question 4

Types of MENs?

Answer 4

Type 1

Type 2A and 2B

Question 5

What is the prevelence of MEN syndromes?

Answer 5

• MEN 1: 2-20/100,000 people
• MEN 2 is less common than MEN 1. Of MEN 2, 2A is the most common and 2B is the rarest.

Question 6

How can so many various endocrine organs be affected in these syndromes?

Answer 6

MEN tumors arise from APUDS (amine precursor uptake and decarboxylation) cells, which make up our endocrine organs.

• Convert AA –> [biogenic amines or peptides] via L-DOPA decarboxylase, which act as hormones or neurotransmitter.
• A mutation in APUD cells can cause neoplastic tumors of related cell types in different endocrine organs.

Question 7

What the common features of APUD cells?

Answer 7

1. Make biogenic amines: by uptake of amine precursors and amine (DOPA) decarboxylase
2. Make small polypeptide hormones
3. Make membrane-bound neurosecretory granules.

Question 8

MEN-1 are associated with what tumors?

Answer 8

1. Parathyroid adenoma (most common: 95%)

2. Pancreatic endocrine tumors

3. Puitary adenoma

4. Carcinoid tumors

Question 9

MEN-2A are associated with what tumors?

Answer 9

1. Medullary thyroid carcinoma (parafollicular cells)- 100%
2. Bilateral phaeochromacytoma (on adrenal medulla)
3. Parathyroid adenoma

Question 10

MEN-2B are associated with what tumors?

Answer 10

1. Medullary thyroid carcinoma (100%)

2. Mucsal neuromas (100%)

3. Phaeochromacytomas

Question 11

MEN-1 consists of hyperplasia or neoplastic transformation of the

Answer 11

THREE P’s

1. parathyroid glands
2. pancreatic islets
3. pituitary.

Question 12

MEN-2A consists of hyperplasia or neoplastic transformation of the

Answer 12

1. thyroid parafollicular cells (medullary thyroid carcinoma [MTC]),
2. parathyroid glands
3. _adrenal medulla (_pheochromocytoma).

Question 13

MEN-2B consists of hyperplasia or neoplastic transformation of the ______, _____, ____.

Answer 13

1. thyroid parafollicular cells (MTC)
2. adrenal medulla (pheochromocytoma)
3. mucosal neuromas.

Not parathyroid

Question 14

Assx condition with pancreas, pituitary adenoma in MEN 1

Answer 14

1. ZE syndrome
2. Pituitary adenoma that can cause acromegaly, cushing syndrome, galloctorrhea.

Question 15

Assx condition with parathyroid neoplasm MEN 1

Answer 15

1. Hyperparathyroidism
2. Hypercalcemia

Question 16

Assx conditions with MEN IIa

Answer 16

1. Hyperparathyroidism

2. Hypercalcemia

3. Medullar carcinoma

4. Increased calcitonin

5. Increased catecholamines

Question 17

Assx conditions with MEN IIb

Answer 17

1. Mucosal nodules
2. Marafanoid body. habitus
3. medullary carcinoma
4. Increased calcitonin
5. Increased catecholamines.

Question 18

MEN type 1 is also called what?

Answer 18

Wermer syndrome

Question 19

What. is MEN type 1, Wermers syndrome?

Answer 19

A mutation in the MEN1 gene, which encodes the menin protein, a tumor supressor. Thus, a mutation would cause unregulated division -> tumor in the 3 P’s: pancreas, parathyroid and pituiary.

Question 20

_______ tumors are also frequently reported in MEN 1 patients.

Where do they occur?

Answer 20

Carcinoid tumors

Men-> thymus

Women-> bronchial carcinoids

Question 21

How can we diagnose MEN Type 1?

Answer 21

Three means:

• Clinical: two or more MEN assx tumors
• Familial: patient with one MEN-1 associated tumor and a 1st degree relative with MEN 1
• Genetic: an asymptomatic carrier of MEN-1 mutation with no biochemical manifestions.

Question 22

Discuss MEN- 1 and the parathyroid glands

Answer 22

• In MEN-1, the most involved organ is the parathyroid gland. All 4 glands will have hyperplasia.
• First manifestation of syndrome: hyperparathyroidism, however it may not. be detected until a clinical sx of the pituitary or pancreas is noticed.

Question 23

What is the second most common manifestation of MEN1?

Answer 23

Neoplastic tumors of pancreatic islet cells that can be benign or malignant.

Question 24

The 2nd most common manifestation of MEN-1 is pancreatic islet tumor that can be benign or malignant.

1. What is the most frequent manifestation?
2. What is the 2nd most common type of functional pancreatic tumor?

Answer 24

1. Gastrinomas: 1/3 of patients with gastrinomas have MEN1.
2. Insulinomas

Question 25

Patients with MEN-1 can have pituitary adenomas. Describe the types and results of them

Answer 25

1. **Prolactin** secreting pituitary tumors are the most common in MEN1; causing galactorrhea and amenorrhea in W and impotence in M). 2. **ACTH** pituitary adeomas -\> Cushing 3. **GH** secreting tumors -\> acromegaly

Question 26

What is **gallactorrhea** **amenorrhea** and **impotence?**

Answer 26

Gallactorrhea- milk discharge Amenorrhea- no menstruation (period) impotence- cant get an erection

Question 27

What is the **3rd most common manifestation of MEN-1**

Answer 27

Symptoms of **hyperprolactinemia**: d/t. a prolactin secreting pituitary adenoma causing _gallactorrhea_, _amenorhea_ and _impotence_.

Question 28

Patients with MEN-1 syndrome have ____________ of both **functional and nonfunctional adrenal cortical hyperplasias/ adenomas.**

Answer 28

**increased frequency.**

Question 29

Tx for MEN1

Answer 29

1. **Surgical resection of hyperplastic parathyroid tissue** 2. **Surgical resection of pituitary adenoma or give meds,** such as _bromocriptine_ for prolactinomas (a DA AGO -\> nihibits prolactin) 3. **Subtotal pancreatectomy** (remove as many multifolcal tumors in pancreas). However, if pancreas is affected surgery will not cure.

Question 31

What causes **MEN type 2**?

Answer 31

MEN type 2 -\> d/t a **mutation in RET protooncogene**, which codes for receptor tyrosine kinase that is needed for cell growth. Mutation will **increase growth.**

Question 32

What. is the most common sign of MEN2?

Answer 32

**Medullary thyroid carcinoma [MTC] of the parafollicular C cells**, which secrete calcitonin.

Question 33

50% of ppl with MEN-2 develop what?

Answer 33

**Pheochromacytomas**

Question 34

Which is worse: MEN 2A or 2B

Answer 34

2B: Average age of death is 30 2A is 60.

Question 35

MEN-2A is also called what?

Answer 35

**Sipple syndrome**

Question 36

In **MEN-2A,** describe what happens to the parafollicular cells.

Answer 36

* Go from a state of _C-cell hyperplasia_ -\> _nodular hyperplasia_ -\> _malignant degeneration over time._ * MTC will also express peptides that C-cells usually dont excrete: somatostatin, TRH, VIP, POMC (so hyperpigmentation) etc.

Question 37

In **MEN-2A,** describe the pheochromacytomas.

Answer 37

These will secrete more EPI than sporadic pheos

Question 38

What MEN disorder where we might see a _itchy skin condition_ and what is it called?

Answer 38

**MEN2A- Cutaneous lichen amyloidosis**

Question 39

Describe the **MTCs** in **MEN-2B**.

Answer 39

**More aggressive, forming metastatic lesions**