Multiple Endocrine Neoplasia Flashcards
Multiple endocrine neoplasia typically involves ____ endocrine glands and tumors may be benign or malignant
What are the hallmarks of malignancy?
Two
Metastasis; invasion
Genetic inheritence of Multiple Endocrine Neoplasia
Autosomal dominant trait (with high penetrance and variable expression)
What is the most common type of MEN?
MEN 1 (followed by MEN 2A, then 2B)
How can so many various endocrine organs be affected in MEN syndromes?
Because they arise from the same type of cells - amine precursor uptake and decarboxylation (APUD) group of cells
APUD cells are comprised of ______ cells distributed throughout the body, and have the capacity to synthesize and/or secrete biogenic _____ formed through the activity of ________ enzyme
Neuroendocrine; amines; L-dopa decarboxylase
Hyperplasia vs. hypertrophy
Hyperplasia = increased number of cells
Hypertrophy = increased size of cells
Abnormal mass of tissue; growth exceeds and is uncoordinated with that of normal tissues; persists after cessation of stimuli
Neoplasm
MEN 1 is associated with what other endocrine condition 95% of the time?
Hyperparathyroidism
MEN 2A and B often occur in combination with what type of tumor?
Medullary thyroid carcinoma
About 100% of cases of MEN2B occur in the setting of what other endocrine conditions? (And thus can be used to differentiate 2A and 2B)
Mucosal neuromas
Marfanoid habitus
Pituitary adenoma is typically associated with what type of MEN?
MEN 1
40-50% of tumors associated with MEN 2A and B are _____
Pheochromocytomas
An enteropancreatic tumor would most likely be associated with what type of MEN?
MEN 1
MEN1 is also known as _____ syndrome
Wermer
MEN 1 involves a gene mutation encoding the ____ protein, which typically functions as a _____________, so mutations cause unregulated cell division and thus tumor formation
Menin; tumor suppressor
3 P’s of Men 1
Parathyroid
Pancreas (endocrine)
Pituitary
______ tumors are frequently reported in MEN 1 patients, which males have a predilection for in the ________, whereas _____ type occurs almost exclusively in women
Carcinoid; thymus; bronchial
PPM of MEN 2A
Pheochromocytoma
Parathyroid (hypercalcemia)
Medullary thyroid cancer
PMM of MEN 2B
Pheochromocytoma
Mucocutaneous tumors
Medullary thyroid cancer
What are the 3 means of diagnosing MEN 1?
Clinical: based on presence of 2 or more MEN-1 associated tumors
Familial: patient with one MEN-1 associated tumor + first degree relative with MEN 1 dx
Genetic: asymptomatic carrier of MEN 1 mutation (no biochemical manifestation)
Although the parathyroid gland is the most frequently involved organ in MEN 1, and ______ usually the first manifestation of the syndrome, presence may NOT be detected until clinical diagnosis of ____ or _____ brings the patient to medical attention
Hyperparathyroidism; pituitary; pancreas
Hyperparathyroidism associated with MEN 1 results in hyperplasia in ___/4 parathyroid glands
4
Second most common manifestation of MEN 1
Neoplastic transformation of pancreatic islet cells (may be benign or malignant)
Neoplastic transformation of pancreatic islet cells is the second most common manifestation of MEN 1.
Of these, what are the 2 most frequent types?
Most frequent = gastrinoma - often ZE syndrome (1/3 of patients with gastrinomas are associated with MEN 1)
Second most = Insulinomas
[other types may include glucagonomas, somatostatinomas, and VIPomas]
42-50% of patients with MEN 1 have pituitary tumors. Most are functionally active and secrete ______; high levels of this hormone are the 3rd most common manifestation of MEN 1, causing ____ and _____in females, and _____ in males
Prolactin; galactorrhea; amenorrhea; impotence
MEN 1 patients may develop tumors secreting ___ (Cushing syndrome) or ______(acromegaly)
ACTH; GH
T/F: MEN 1 pts have an increased frequency of both functional and nonfunctional cortical hyperplasia or adenomas
True
Tx options for MEN 1
Surgical resection of hyperplastic parathyroid
surgical resection of pituitary adenomas or pharmacotherapy (bromocriptine for prolactinomas; octreotide for acromegaly)
Subtotal pancreatectomy (surgical cure for associated pancreatic tumors is not usually possible)
Drug tx for prolactinoma-associated MEN1
Bromocriptine
Drug tx for acromegaly-associated MEN1
Octreotide
MEN 2 is caused by an activation mutation of the ____ protoconcogene, which codes for a RTK that phosphorylates and activates enzymes critical to cellular development
RET
What is the most common sign of MEN2?
Malignant transformation of parafollicular C cells = medullary thyroid carcinoma (MTC)
Medullary thyroid carcinoma is the most common sign of MEN 2, meaning malignant transformation of the C cells has occurred. What are the normal functions of C cells?
Secretion of calcitonin (normally scattered throughout the thyroid gland)
MEN 2 is divided into type 2A and type 2B. Which type is associated with more severe mortality overall?
MEN2B
[avg death for 2A = 60y/o, avg death for 2B = 30y/o]
T/F: medullary thyroid cancer is often bi-lobed
True
Neoplastic C-cell hyperplasia involves expanding C-cell masses disrupting the the _____ membrane surrounding individual ______ follicles
Basal; thyroid
MEN2A consists of neoplastic transformations of what 3 major structures? This is also known as what syndrome?
Parathyroids
Thyroid parafollicular C cells
Adrenal medulla
Sipple syndrome
_______ cells in patients with MEN 2A characteristically progress through a state of ______ cell hyperplasia to nodular hyperplasia to malignant degeneration over a variable period
Parafollicular; C-cell
Medullary thyroid cancer associated with MEN2A Sipple syndrome also expresses peptides and hormones NOT commonly elaborated by C-cells - what are some examples?
Somatostatin TRH VIP POMC Carcinoembryonic antigen (CEA) Neurotensin
Pheochromocytomas associated with MEN 2A secrete greater amounts of _____ than sporadic pheochromocytomas
Another condition called ______ may be present, characterized by pruritic, scaly, papular, pigmented skin lesion located in interscapular region or on extensor surfaces of extremities. Associated _____ deposition has been documented histologically
Epinephrine
Cutaneous lichen amyloidosis; amyloid
Is it more frequent to find hyperparathyroidism in MEN 1 or MEN 2A?
MEN 1
[although the type of hyperparathyroidism and its manifestations are similar]
What makes up the MEN 1 “Diamond” diagram?
Pituitary
Parathyroid — Parathyroid
Pancreas
What makes up the MEN 2A “Square” diagram?
Parathyroid — Parathryoid
Pheo (adrenals) — Pheo (adrenals)
What makes up the MEN 2B “Triangle” diagram?
Oral
Pheo (adrenals) — Pheo (adrenals)
MEN 2B is associated with medullary thyroid cancer, pheochromocytoma, and younger age of death.
What are the other 3 identifying characteristics of MEN 2B?
Mucosal neuromas
Intestinal ganglioneuromas (similar to hirschprung presentation)
Marfanoid body habitus
Describe marfanoid body habitus associated with MEN 2B
Long limbs
Arachnodactyly
Hyperlaxity
T/F: hyperparathyroidism is often associated with MEN 2B
False; not associated
T/F: the MTC associated with MEN 2B is more aggressive than other forms with metatatic lesions as early as infancy
True
