Multiple Endocrine Neoplasia Flashcards
What is significant about the genetics of MENs?
autosomal dominant trait
high degree of penetrance
variable expressivity
What is the prevalence of MEN syndromes?
MEN 1 = 2-20 per 100,000
MEN less common (2B = rarest, 5% of all type 2 cases)
What types of cells do MEN tumors arise from?
Amine precursor uptake and decarboxylation (APUD) cells
make/secrete biogenic amines thru enzyme L-dopa decarboxylase
found in a lot of different organs
make small popypeptide hormones
membrane-bound neurosecretory granules
What types of tumors are found in MEN 1 and what is their prevalence?
PT adenoma = 95%
pancreatic tumors = 50%
pit adenoma = 40%
carcinoid tumors = 30%
what type of tumors only in MEN type 2?
medullary thy carcinoma = 100% in both a and b
pheochromocytoma = 50% of both a and b
What tumors distinguish MEN 2A and 2B?
In both: medullary thy cancer, pheochromocytoma
Only in 2a: Parathyroid carcinoma
Only in 2B: neuromas
What type of MEN has pancreatic and pituitary tumors?
MEN1
What type of MENs have parathyroid adenomas?
MEN1
MEN2A
What type of MEN has marfanoid habitus?
MEN 2B (100%)
What is the genetic cause of MEN 1?
2 copies of mutated MEN1 –> encodes menin protein = tumor suppressor
mutation –> unregulated cell division –> tumor
What is Wermer syndrome?
MEN type 1
In what type of MEN are carcinoid tumors common?
type 1
males: common in thymus
women: bronchial
What are the 3 means of diagnosing MEN 1?
clinical: 2 or more Men 1-associated tumors
familial: pt w/ one men tumor and 1st degree relative w/ men1
genetic: asymptomatic carrier of men1
What is usually the first manifestation of MEN type 1?
hyperparathyroidism
PT gland tumors in 95% of cases –> hyperplasia of all four glands
What is the second most common manifestation of men type 1?
cancer of pancreatic islet cells
most frequent = gastrinoma (1/3 of all gastrinomas assoc w/ MEN1)
insulinoma = 2nd most common –> hypoglycemia
What type of men has pituitary tumors?
What type of tumor are they usually?
Men type 1 (~50% of cases)
prolactinoma most common kind
most of them are functionally active
What is the treatment for MEN 1?
surgical resection of associated adenomas
or medication management of pituitary tumors (bromocriptine for prolactinoma)
subtotal pancreatectomy, but surgical cure for these tumors is usually not possible
What is MEN type 2 caused by?
by 1 gain of fxn mutation in RET protooncogene
RET encodes for RTK that Piates and activates enzymes critical to cell development
What is the most common sign of men 2?
medullary thyroid carcinoma =
transformation of parafolicular/C cells of thyroid –> detect high calcitonin
abt 50% also get pheochromocytoma
Of the type 2 MENs, which is more severe?
type 2B
avg age of death is ~30
in type a avg age of death is ~60
What is Sipple syndrome?
Men 2A
What is distinct about the pheochromocytomas in MEN 2 vs sporadic types?
secrete greater amounts of epinephrine than sporadic type
In what type of MEN is cutaneous lichen amyloidosis sometimes present?
type 2A
What is distinct about the medullary TC in MEN 2B?
more agressive
metastatic lesions have been described in infancy
