Lecture 12: Multiple Endocrine Neoplasia

Question 1

Define MEN-1

Answer 1

MEN-1 consists of hyperplasia or neoplastic transformation of the parathyroid glands, pancreatic islets, and pituitary (3 P’s)

Question 2

Define MEN-2A

Answer 2

MEN-2A consists of hyperplasia or neoplastic transformation of the thyroid parafollicular cells (medullary thyroid carcinoma [MTC]), parathyroid glands, and adrenal medulla (pheochromocytoma).

Question 3

Define MEN-2B

Answer 3

MEN-2B consists of hyperplasia or neoplastic transformation of the thyroid parafollicular cells (MTC) and adrenal medulla (pheochromocytoma) with concomitant development of mucosal neuromas.

Question 4

How many endocrine glands typically involved in MEN; what type of inheritance pattern?

Answer 4

• At least 2 endocrine glands
• Autosomal dominant

Question 5

Where do MEN tumors arise from; why is this significant?

Answer 5

• Amine precursor and uptake decarboxylation (APUD) group of cells
• A diffuse system of neuroendocrine cells distributed throughout the body (GI, respiratory mucosa, pituitary, parathyroid, pancreatic islets…)

Question 6

What does APUD denote the capacity of these cells to do; via which enzyme?

Answer 6

Synthesize and/or secrete biogenic amines formed through activity of the enzyme L-dopa decarboxylase

Question 7

In MEN 1 there is a gene mutation of?

Answer 7

• Menin protein
• Normally functions as a tumor supressor, but mutations lead to unregulated cell division —> tumor formation

Question 8

What type of tumors are frequently reported in MEN 1 pts?

Answer 8

Carcinoid

Question 9

What are the 3 means of diagnosing MEN 1?

Answer 9

1) Clinical - 2 or more MEN-1 associated tumors
2) Familial - pt w/ one MEN-1 associated tumor PLUS a first degree relative w/ MEN-1 dx
3) Genetic - asymptomatic carrier of MEN-1 mutation (no biochemical manifestation necessary

Question 10

What is the most frequently involved organ in MEN 1 and is a result of hyperplasia of?

Answer 10

• Parathyroid gland —> Hyperparathyroidism
• Hyperplasia of ALL 4 glands

Question 11

What is the second most common manifestation of MEN 1 and what is seen with this?

Answer 11

• Neoplastic transformation of pancreatic islet cells
• Gastrinomas are most frequent (Zollinger Ellison)
• Insulinomas are second most common
• May also see glucagonomas, somatostatinomas, and VIPomas

Question 12

What is the third most common manifestation of MEN 1 and what is seen with this?

Answer 12

• Pituitary neoplasia causing Hyperprolacinemia
• Females will have galactorreha and amenorrhea
• Males will suffer from impotence
• Some pts may develop tumors secreting ACTH (Cushing syndrome) or GH (acromegaly)

Question 13

What are the treatment options for MEN-1?

Answer 13

• Surgical resection of hyperplastic PT
• Surgical resection of pituitary adenomas or pharmacotherpay (bromcocriptine for prolactinomas; octreotide for acromegaly)
• Subtotal pancreatectomy (surgery on the pancreas is NOT always possible)

Question 14

MEN-2 is caused by an activation mutation of?

Answer 14

RET proto-oncogene

Question 15

What is the most common sign of MEN 2?

Answer 15

• Malignant transformation of the parafollicular (C cells) = Medullary thyroid carcinom (MTC)
• Some patients will develop pheochromocytoma of the adrenal gland

Question 16

What happens to the parafollicular cells in patients with MEN-2A (sipple syndrome); what is often seen in the patients because of this?

Answer 16

• Characteristically progress through a state of C-cell hyperplasia to nodular hyperplasia to malignant degeneration over a variable period
• MTC also expresses peptides and hormones NOT commonly seen produced by C-cells, including somatostatin, TRH, VIP, POMC, carcinoembryonic antigen (CEA), and neurotensin

Question 17

What is different about the Pheochromocytomas associated w/ MEN 2A?

Answer 17

Secrete greater amounts of epinephrine than sporadic pheochromocytomas

Question 18

Cutaneous lichen amyloidosis is often seen with?

Answer 18

• Itchy skin condtion commonly seen with MEN 2A
• Located in the interscapular region or on the extensor surfaces of the extremities

Question 19

What MEN categories is hyperparathyroidism assosciated with?

Answer 19

• Seen in almost ALL MEN-1 cases
• Associated with MEN-2A, but seen far less frequently

Question 20

What are the distinguishing pathologies for MEN-2B?

Answer 20

• MTC (also seen in 2A)
• Pheochromocytomas
• Mucosal neuromas

- Intestinal ganglioneuromas (Hirschsprung’s)

- Marafanoid body habitus

Question 21

We have a saying for Primary Hyperparathyroidism; what is often seen symptom wise?

Answer 21

• “Painful bones, renal stones, abdominal groans, and psychic moans.”
• Bone disease: fractures from osteoporosis

- Renal disease: chronic renal insufficiency –> polyuria and secondary polydipsia

- GI: constipation, nausea, peptic ulcers, pancreatitis, and gallstones

• CNS/Neuromuscular: depression, lethargy, weakness, and fatigue