MEN Syndromes B&B

Question 1

what is the genetic inheritance pattern of MEN syndromes? (multiple endocrine neoplasia)

Answer 1

rare, but all autosomal dominant - germline mutations

Question 2

MEN 1 presents as…

Answer 2

3 P’s: pituitary adenoma, parathyroid adenoma, pancreatic tumors

Question 3

MEN 1 is due to a germline mutation in…

Answer 3

menin (tumor suppressor) on MEN1 gene (11q13)

classic example of “2 hit” hypothesis - patients are born with 1 normal gene, second “hit” occurs in endocrine glands later in life

Question 4

what is the first finding in most patients with MEN1 and how does it present?

Answer 4

MEN 1: 3 P’s (pituitary adenoma, parathyroid adenoma, pancreatic tumors)

first finding is usually parathyroid adenoma - presents with hyperparathyroidism, may cause recurrent kidney stones from hypercalcemia

Question 5

pituitary adenoma is not commonly seen in MEN syndromes except for which type?

Answer 5

MEN1: 3 P’s (pituitary adenoma, parathyroid adenoma, pancreatic tumors)

most commonly a prolactinoma, 2nd most common is GH secreting adenoma

Question 6

what kind of pancreatic tumors occur in MEN 1?

Answer 6

MEN 1: 3 P’s (pituitary adenoma, parathyroid adenoma, pancreatic tumors)

more specifically form pancreatic-duodenal neuroendocrine tumors (can be anywhere along this tract)

most commonly form gastrinomas —> Zollinger-Ellison syndrome (multiple peptic ulcers)

rarely cause insulinomas, gastrinomas, VIPomas

Question 7

what do MEN 2A and 2B cause?

Answer 7

cause “medullary tumors”:

medullary thyroid carcinoma (parafollicular/C cells —> hypocalcemia) usually occurs first,

followed by pheochromocytoma (of adrenal medulla)

Question 8

how do MEN2A and MEN2B differ in presentation?

Answer 8

both present with “medullary tumors” - medullary thyroid carcinoma and pheochromocytoma (of adrenal medulla)

MEN2A: also presents with parathyroid adenomas, but NO physical findings

MEN2B: also presents with 2 M’s - Mucosal neuromas (benign growths of nerve tissue) and Marfanoid appearance (tall, long wingspan), usually but no parathyroid involvement

Question 9

what germline mutation is the cause of MEN 2A and 2B?

Answer 9

AD GOF mutation in RET (chromosome 10)

proto-oncogene which codes for receptor tyrosine kinase important for cell growth/differentiation

Question 10

for which type of MEN syndrome is thyroidectomy often done prophylactically at a young age?

Answer 10

MEN2A/B: GOF RET mutation causes “medullary” tumors - medullary thyroid carcinoma and pheochromocytoma (of adrenal medulla)

chance of thyroid cancer is ~100% in lifetime if thyroid is not removed

Question 11

which MEN syndromes do the following indicate?
a. pituitary adenoma
b. medically thyroid carcinoma
c. parathyroid adenoma
d. pheochromocytoma
e. mucosal neuromas
f. Marfanoid body

Answer 11

a. pituitary adenoma = MEN1
b. medically thyroid carcinoma = MEN2 (A/B)
c. parathyroid adenoma = MEN1 or MEN2A
d. pheochromocytoma = MEN2 (A/B)
e. mucosal neuromas = MEN2B
f. Marfanoid body = MEN2B