Multiple Endocrine Neoplasias Flashcards
(22 cards)
Multiple endocrine neoplasia syndromes typically involve Neoplasias of at least ______ kinds of _______ glands
Two kinds of endocrine glands
MEN syndromes are typically autosomal _______ with a ____ degree of penetrance and _______ expressivity
Autosomal dominant with high degree of penetrance and variable expressivity
Most common type of MEN
MEN 1
MEN 2B is least common
MEN tumors arise from what cell type
Amine precursor uptake and decarboxylatino (APUD) group of cells
Role of APUD cells
Constitute the diffuse system of neuro endocrine cells distributed throughout the body
APUD denote the capacity of these cells to synthesize and/or secrete biogenic amines formed through activity of the zone
L-dopa decaroxylase
Enzyme that gives APUD cells their function (also what is their function)
L-dopa decarboxylase
APUD cells have capacity to synthesize/secrete biogenic amines
Other functions of APUD cells
Biogenic amine synthesis
Amine precursor uptake
Amine decarboxylase
Small polypeptide hormone synthesis
Membrane bound neurosecretory granules
Tumors associated with type 1 MEN
Pancreatic (ONLY SEEN IN TYPE 1)
Pituitary
Parathyroid
Carcinoid
Tumors associated wth type 2A MEN
Thyroid
Parathyroid
Adrenal (phaeochromocytoma)
Tumors associated with type 2B MEN
Neuromas *** (only seen in type 2B)
Thyroid
Phaechromocytoma
Conditions associated with type 1 MEN
Hyperparathyroidism Hypercalcemia ZE syndrome Various pituitary path (Acromegaly, Cushing syndrome, galactorrhea)
Conditions associated with type 2A MEN
Hyperparathyroidism Hypercalcemia Medullary carcinoma Increased calcitonin Increased catecholamines
Conditions associated with Type 2B MEN
Mucosal nodules ***
Marfanoid body habitus *
Medullary carcinoma
Increased calcitonin
Increased catecholamines
Gene defect leading to type I MEN
Mutations in the MEN1 gene that codes for menin*
Menin usually acts as tumor suppressor
Mutation of menin leads to unregulated cell division —> tumor
3Ps of Type 1 MEN
Parathyroid
Pancreas
Pituitary
Three ways to Dx MEN1
Clinical: two or more MEN-1 associated tumors
Familial: patient with one MEN1 associated tumor and first degree relative with MEN1
Genetic: asymptomatic carrier of EN1 mutation (no biochemical manifestations)
First symptom to present with type 1 MEN
Hyperparathyroidism
Second most common manifestation of MEN1
Pancreatic islet neoplasm
Most often leads to gastrinoma
Insulomas second most common
Can also get glucagoma, somatostinoma, VIPoma
Symptoms of hyperplasia of the pituitary
Occur in ~50% of MEN1
Most secrete prolactin
Leads to galactorrhea and amenorrhea in women/impotence in men
Third most common manifestation of MEN1
May develop ACTH/GH secreting humor with Cushing/acromegaly
Treatment for MEN1 involves
Surgical resection of hyperplastic parathyroid tissue
Surgical resection of pituitary adenomas/management with bromocriptine for prolacitnomas/octreotide for acromegaly
Subtotal pancreatoctomy (surgical cure of associated pancreatic tumors not usually possible)
MEN type 2 results from an activating mutation of what gene
RET protooncogene
RET gene codes for RTK that phosphorylates—> activates enzymes critical to cellular dev
Most common sign of MEN2
Malignant transformation of parafollicular cells (c cells) resulting in medullary thyroid carcinoma
C cells normally secrete calcitonin (bone tone)
