MEN

Question 1

Multiple endocrine neoplasia (MEN)

Answer 1

Characterized by the occurrence of tumors involving 2 or more endocrine glands in a single patient

2 major forms MEN 1 and MEN 2
Inherited autosomal dominant or sporadically

Question 2

Tumors and findings identified in MEN syndromes part 1

Answer 2

Parathyroid adenomas- functional, PTH-secreting benign neoplasms arising from normal PT tissue that lead to high serum Ca, low PO4, and non suppressed or elevated PTH concentration

Pheochromocytoma- catecholamine- secreting tumors that arise from chromaffin cells of the adrenal medulla, can present with HTN, headaches, palpatations, and diaphoresis

Enteropancreatic tumors: neuroendocrine tumors of intestine and pancreas, examples- gastrinoma, insulinoma, glucagonoma, and nonfunctioning pancreatic tumors

Pituitary Adenomas- tumors of the anterior pituitary gland, can be functtionL or non, secrete prolactin ACTH, growth H, LH FSH, TSH

Medullary thryoid cancer- Neuroendocrine tumor arising from the parafollicular C cells of the thyroid, can secrete clacitonin 75% of cases are sporadic, 25% are familial

Marfanoid habitus- decrease upper body / lower body ratio, abnormal posterior postion of manible, decreased cephalic index (head width/length), no ectopic lentis or aortic abnormalities

Question 3

MEN1

Answer 3

11q13–> MEN
Parathyroid Adenoma, Pituitary adenoma, enteropancreatic tumors

PPP (Parathyroid, pituitary, pancreatic)

Question 4

MEN2 A

Answer 4

10 cen- 10 q 11.2 (RET)

Medullary thyroid, pheochromocytoma, parathyroid hyperplasia

PTA (Parathyroid, Thyroid, Adrenal)

Question 5

MEN 2B/3

Answer 5

10 cen 10q 11.2

Medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid habitus

NO P, TA (Not parathyroid but mucosal neuromams and marfinoid habitus, T-thyroid, A- adrenal)

Question 6

MEN 1 Diagnosis

Answer 6

Clinical- A patient with 2 or more MEN 1 syndromes (PPP)

Familial- a patient with 1 MEN 1 associated tumor and a 1st degree relative with MEN 1

Genetic- a person who has one MEN1 mutation but does not have a clinical or biochemical manifestation of MEN 1, that is a mutant carrier

3 different means to diagnose a patient with MEN 1: Clinical, familial or genetic means

Pts diagnosed clinically might not have a germline mutation, fam members with MEN 1 may have variable presentations, recognizing MEN1 is helpful for prevention

Question 7

MEN 1 gene

Answer 7

A tumor suppressor gene

Chromosome 11 Q 3

Regulated transcritption, genome stability, cell division and proliferation
Inheritance of a germline MEN1 Mutation predisposes a person to develop a tumor that arises after a somatic mutation
Most MEN 1 germline mutations are inactivating, >10% of MEN 1 germline mutations arise de novo, Unlike MEN 2, lack of genotype/phenotype correlations

Question 8

All individuals offered MEN 1 mutation testing should be provided genetic counseling before testing

Answer 8

Asypmtomatic relative of a pt with or without MEN1 germline mutation

Germline mutation–> tumor surveillanenc
No mutioaion– many testing of levels

Question 9

MEN 2

Answer 9

Autosomal dominant, tumors (medullary thyroid carcinoma MTC, pheochomocytoma, primary hyperparathyroidism)

Germline mutation in the RET proto oncogene: RET rearranged during transfection

Subtypes MEN 2A, MEN2B, familial MTC