MEN Flashcards
How is MEN inherited?
as an autosomal dominant trait with a high degree of penetrance and variable expressivity
What are the major forms of MEN syndromes?
Type 1, type 2 (2A and 2B) and type 4
What is the prevalence of MEN 1
Estimated to vary btwn 2-20 per 100,000
What is the prevalence of MEN 2
Less common than MEN 1
2A most common form of type 2
2B: relatively uncommon, 5% of all type 2 cases
Where do MEN tumors arise from?
Amine precursor uptake and decarboxylation (APUD) group of cells, they constitute the diffuse system of neuroendocrine cells distributed throughout the body
Inherited genetic defects affect different groups of APUD cells and lead to neoplastic development of related cell types in diverse anatomic regions
What do APUD cells do?
synthesize and/or secrete biogenic amines formed through activity of L-dopa decarboxylase
What are the common features of APUD cells?
Biogenic amine synthesis Amine precursor uptake Amine (DOPA) decarboxylase Small polypeptide hormone synthesis Membrane-bound neurosecretory granules
What kind of tumors will exhibit in MEN 1
Parathyroid adenoma ~95% Pancreatic endocrine tumor ~50% Pituitary adenoma Carcinoid tumor Functional and non-functional adrenal cortical hyperplasia or adenomas
What kind of tumors will exhibit in MEN 2A?
Medullary thyroid carcinoma ~ 100%
Bilateral phaeochromocytoma ~50%
Parathyroid adenoma
What kind of tumors will exhibit in MEN 2B?
Neuromas ~ 100%
Medullary carcinoma of the thyroid ~ 100%
Marfanoid habitus ~ 100%
Phaeochromocytoma ~50%
What are the conditions associated with MEN 1
Hyperparathyroidism Hypercalcemia Zollinger-Ellison syndrome Acromegaly of pituitary: Tumor-secreting GH Cushing: tumor secreting ACTH Galactorrhea
What are the conditions associated with MEN IIa?
Hyperparathyroidism
Hypercalcemia
Increased calcitonin
Increased catecholamines
What are the conditions associated with MEN IIb?
Mucosal nodules
Marfanoid body habitus
Increased calcitonin
increased catecholamines
What is MEN type I caused by?
mutations in MEN 1 gene, which encodes a protein known as menin: tumor suppressor
Mutations in menin causes unregulated cell division that leads to tumor formation
Describe the different manifestations of MEN 1 that can occur between male vs female
Male: predilection for developing carcinoid tumors within the thymus
Female: bronchial carcinoids
What are the three means of diagnosing MEN 1?
Clinical: two or more MEN 1- associated tumors
Familial: pt with 1 MEN 1 associated tumor and a first-degree relative with MEN 1
Genetic: asymptomatic carrier of MEN 1 mutation
In MEN 1, what is the most frequently involved organ?
Parathyroid glands and hyperparathyroidism is the first manifestation
Hyperplasia of all four glands
When is the presence of MEN 1 detected?
disease of the pituitary or pancreas has brought the pt to medical attention
What is the second most common manifestation of MEN 1?
neoplastic transformation of the pancreatic islet cells: Benign or malignant
Most frequent manifestation of pancreatic involvement is gastrinoma (1/3)
What are the second most common type of functional pancreatic tumor in MEN 1?
insulinomas
*others include: glucagonomas, somatostatinomas, VIPomas
Describe most pituitary tumors found in MEN 1
Functionally active and secrete prolactin
Symptoms: hyperprolactinemia, galactorrhea and amenorrhea in women
Impotence in men
Symptoms are 3rd most common manifestations of MEN 1
What is the Tx for MEN 1?
Surgical resection of hyperplastic parathyroid tissue
Surgical resection of pituitary adenomas or pharmacological management with bromocriptine (prolactinomas) and octreotide (acromegaly)
Subtotal pancreatectomy - not usually possible
What mutation causes MEN type 2?
RET protooncogene: gene codes for a receptor tyrosine kinase that phosphorylates and activates enzymes critical to cellular development
What is the most common sigh of MEN 2?
malignant transformation of parafollicular cells or C cells = medullary thyroid carcinoma (MTC)
Which MEN type 2 is more severe?
MEN 2B - 30 years avg age
MEN2A- 60
What is another name for MEN 1?
Wermer syndrome
What is another name for MEN 2A?
Sipple syndrome
What does MEN2A consists of?
neoplastic transformation of parathyroids, thyroid parafollicular C cells and adrenal medulla
Parafollicular cells in pts with MEN 2A characteristically progress through a state of C-cell hyperplasia to what over time?
nodular hyperplasia to malignant degeneration over a variable period
Medullary thyroid carcinoma (MTC) expreses peptides and hormones not commonly elaborated by ___ cells, including what?
C
Somatostatin, TRH, VIP, POMC, carcinoembryonic antigen, and neurotensis
Pheochromocytomas with MEN 2A secrete greater amounts of _______ than sporadic phenochromatcytomas
epinephrine
What is cutaneous lichen amyloidosis?
an itchy skin condition, might be present in some cases of MEN 2A
hyperparathyroidism (is/is not) associated with MEN 2B
is not
What type of MEN?
MTC, pheochromocytoma, primary hyperparathyrroidism, cutaneous lichen amyloidosis, Hirschprung?
2A
What type of MEN?
MTC, pheochromocytoma, mucosal neuromas, intestinal ganglioneuromas, marfanoid habitus, NO hyperparathryoidism
2B
What are the symptoms of gastrinomas associated with MEN 1
Prolific production of gastric acid with resultant duodenal and jejunal ulcers and diarrhea
What do MEN syndromes typically involve?
Tumors (neoplasia) in at least two endocrine glands
Tumors can be noncancerous (benign) or malignant
