MEN - Exam 4 Flashcards
How are MEN disorders inherited? development of tumors in _____ endocrine glands. Are they benign or cancerous?
autosomal dominant traits
two or more
Tumors may be malignant or benign
What is another name for MEN1? What is the mutation in? What is the result? When does it usually manifest by? What are the 3 MC organs involved?
Wermer syndrome
mutation in menin
mutation prevents tumor suppression because the role of menin is tumor suppressor protein
manifests by 40
parathyroid
pancreas
anterior pituitary
What is the appropriate imaging for the follow organ/systems? Chest, abdomen, pelvis, brain, parathyroid
CT - chest, abdomen, pelvis
MRI - brain
Nuclear scan - parathyroid
What is the primary pt with primary hyperparathyroidism?
elderly (60-70) female with elevated calcium
What is the MC initial presentation of MEN1? What age? What gender? How do you confirm tumor location?/
Parathyroid tumor occurs in over 90% of patients
20-25 both men and women
nuclear scan
What is the tx for primary hyperparathyroidism? What is the additional tx? What do these pts need to avoid?
sx either 3 1/2 PT glands or all 4
cinacalcet
avoid oral calcium and thiazide diuretics because thiazide diuretics retain calcium and excrete K
What is the MOA for cinacalcet?
binds to CaSRs in the parathyroid gland, increasing the glands’ affinity for extracellular calcium, thereby decreasing PTH secretion
What does GEP-NET’s stand for? What are the 5 types? Which one is the MC? 2nd MC?
Gastro-Entero-Pancreatic NeuroEndocrine Tumors (GEP-NET’s)
**Gastrinoma - MC
**Insulinoma - 2nd MC
Glucagonoma
Vasoactive Intestinal Peptide (Vip) Tumors (VIPomas)
Pancreatic Polypeptide-Secreting Tumors (Ppomas) and Non-functioning Pancreatic NETs
What is the MC MEN pancreatic tumor? How common are they? Specifically, where as they commonly found?
Gastrinomas: (gastrin-secreting pancreatic tumor)
Occurs in 40% of patients with MEN1
small, multiple, ectopic most are found in duodenum
What is the function of gastrin?
a hormone that stimulates secretion of gastric acid and assists in gastric motility
How do gastrinomas present? ______ further stimulates gastrin secretion
s/s due to hyperacidity of stomach so gastritis, PUD, GERD, diarrhea
Hypercalcemia
What are the 4 functions of gastric acid?
stimulates gastrin
Gastric secretion
Gastric acid secretion
secretin release
What 5 things stimulate gastrin release?
Ingestion of:
peptides
amino acids
gastric distention
an elevated stomach pH
hypercalcemia
Gastrin stimulates secretion of _____ in the cells of the lining of the stomach which _____
hydrochloric acid (gastric acid)
lowers the pH.
When gastric acid passes into the _____ it stimulates the release of ____ from duodenal cells due to _____.
duodenum
secretin
low pH
Secretin inhibits _____ release, _____, and stimulates ____ release. When the pH in the duodenum _____ it shuts off secretin release
gastric acid
gastric motility and secretion
bicarb
ncreases
_____ and _____ work opposite each other
secretin and gastrin
What are the 2 lab tests for gastrinomas?
fasting serum gastrin
secretin stimulation test
What is normal range for a fasting serum gastrin? _____ is suggestive for gastrinoma but _____ is diagnostic
normal range 50-60 pg/mL
> 150 pg/mL is suggestive
> 1000 pg/mL is diagnostic
What is considered a positive secretin stimulation test? **What is the important pt education?
(+) results - serum gastrin levels post administration >120 pg/mL over baseline levels
Must d/c PPI 6 days prior and H2 blocker 1 day prior to testing (need to convert PPI to H2 therapy for the appropriate pts)
aka give the pt secretin which theoretically in a normal person should “turn off” gastrin and should see a drop in gastrin levels but in a pt with a gastrinoma gastrin is constantly produced even in the presence of secretin
What is the management of gastinomas?______ is controversial. Why? When it is recommended?
Long-term high dose proton pump inhibitor (PPI) w/wo histamine 2 receptor antagonist
treat the hypercalcemia
sx is controversial -> long term outcomes are not definitive
most often recommended to prevent liver metastasis
insulinomas occur in what cell type? What age do they present most often?
β-islet cell, insulin-secreting tumors of the pancreas
between 20 and 40
What is the clinical presentation of an insulinoma? When is it worse? When does it improve?
hypoglycemic s/s
worse: fasting or exertion
improves: glucose/carb intake
What is the lab test for insulinomas? What is the drawback of this test? Name 2 additional tests with the results you would expect for an insulinoma
72 hour fast-> most reliable, assess for hypoglycemic symptoms and blood glucose < 55 mg/dL
requires hospital admission for direct supervision aka its expensive
plasma insulin concentration and C-peptide levels-> both will be elevated
What is the management of an insulinoma? What is an alternative tx?
sx!!!!!
medical management while awaiting sx or if not a surgical candidate
frequent carb intake
oral diazoxide (Proglycem)
everolimus (Afinitor)
______ is a potassium channel activator. inhibits the secretion of insulin. What type of tumor does it treat?
oral diazoxide (Proglycem)
insulinoma
_____ is an antitumor agent that induces insulin resistance. What type of tumor does it treat?
everolimus (Afinitor)
aka helps bring BS levels up
insulinoma
What is a glucagonoma? What organ? What is the function of glucagon?
Pancreatic tumor that secretes glucagon
hormone formed in the pancreas that promotes the breakdown of glycogen to glucose in the liver. Naturally occurs when the blood glucose drops
What is the MC presenting symptom for a glucagonoma?
weight loss - MC presenting symptom
hyperglycemia
necrolytic migratory erythema
stomatitis
What is necrolytic migratory erythema
breakdown of skin around all the orifices of the body
What are the lab tests for a glucagonoma?
elevated blood glucose
elevated fasting blood glucagon level > 150 pg/mL
normal fasting is 50-100
What is the management for glucagonoma?
Control blood sugar (same as Diabetes Mellitus management)
Octreotide
Surgical excision
When is a surgical excision recommended for a glucagonoma?
recommended if single lesion is localized at the time of diagnosis
_____ inhibits glucagon at high doses (also inhibits insulin). What tumor type does it treat?
Octreotide
glucagonomas and VIPoma
What is a VIPoma? What are the clinical findings?
Pancreatic tumor that secretes vasoactive intestinal polypeptide
-severe watery diarrhea
-vasodilation (flushing)
-inhibition of gastric acid secretion (iron and B12 def, leads to malnutrition)
-bone resorption (hypercalcemia and osteoporosis)
-enhanced glycogenolysis (high BS)
describe the watery diarrhea that would be present in a pt with VIPoma? What happens as a result? How much volume? What a normal stool volume?
tea colored and odorless
magnesium and potassium are lost in the diarrhea
400ml is normal stool volume
greater than 700ml is present
What is the lab test for a VIPoma? What is the normal range?
serum VIP concentration > 75 pg/mL, confirmed by repeat testing
normal range 0 −59 pg/mL
What is the management of an VIPoma? When is sx an option?
correct fluid, electrolyte and vitamin imbalances aka stablize the pt first
octreotide - inhibits VIP - helps control diarrhea
surgical excision of primary tumor, if no mets at diagnosis
What are Pancreatic Polypeptide-Secreting Tumors(Ppomas) and Non-functioning Pancreatic NETs? When does the problem appear?
These are “non-functioning” tumors that secrete various substances but do not present clinically with a hormonal syndrome
Often asymptomatic resulting in metastasis to the liver
What is the tx for Pancreatic Polypeptide-Secreting Tumors(Ppomas) and Non-functioning Pancreatic NETs? What is the risk?
sx is controversial but need to consider the chance of metastasis, low chance of mets = sx provides a better prognosis
complications that result in iatrogenic diabetes, steatorrhea, early and late dumping syndromes, and other gastrointestinal symptoms
MEN1 pituitary adenomas will MC be _______. What is 2nd, 3rd and 4th.
60% secrete prolactin
<25% secrete growth hormone
10-20% are nonsecretory but can compress pituitary tissue or optic chiasm
5% secrete ACTH (Cushing dz)
What is the testing for a prolactinoma? What is the medication tx?
serum prolactin concentration above 40, slightly high value (20-40) needs to be repeated
dopamine agonist
What is the testing for excessive GH? What is the medication tx?
GH suppression test: FAILURE of GH to reach less than 0.4 within of 1-2 hours of an oral glucose load
octreotide
What are the testing for excessive ACTH? What is the medication tx?
Dexamethasone suppression test
24 urine free cortisol
late night salivary cortisol
pasireotide (Signifor)
_______ inhibits ACTH secretion. What type of tumor is it used in?
pasireotide (Signifor)
excessive ACTH secretion
What is the definitive management for pituitary adenoma?
transsphenoidal adenomectomy +/- radiotherapy for residual unresectable tumor tissue
What are some additional types of tumors that are possible with MEN1?
adrenal adenoma
carcinoid tumor: of the bronchi, GI, pnacreas or thymus
meningioma
lipoma
Facial Angiofibromas and Collagenomas
thyroid tumors
Who needs to be screened for MEN1? What is the prognosis?
Two or more MEN 1–associated endocrine tumors
First-degree relatives of an MEN1 mutation carrier even if they are asymptomatic
genetic testing
Decreased life expectancy, with a 50% probability of death by age 50 years
What is MEN2 characterized by? What is the other name?
a disorder characterized by a predisposition of medullary thyroid carcinoma (MTC), pheochromocytomas, and parathyroid tumors
Sipple syndrome
MEN2 is a genetic mutation in the _______. What is the function of that gene? What does a mutation result in?
RET proto-oncogenes
RET gene provides instruction for producing a signaling protein within nerve cells
Mutation leads to excessive activation resulting in tumor formation
the RET gene is expressed in what 3 places? What are the 3 subtypes? Which one is MC?
thyroid, parathyroid, and adrenal glands
**MC-> MEN2A: MTC, pheo, para
MEN2B (aka MEN 3): MTC, pheo and other skeletal/soft tissue presentations
Family medullary thyroid carcinoma (FMTC)
_____ is the MC feature of MEN 2A and MEN 2B. Where do the malignant cells originate? What do they secrete?
Medullary Thyroid Carcinoma
C-cells of the thyroid
calcitonin
Give s/s of medullary thyroid carcinoma?
solitary thyroid nodule (75-90% of patients)
cervical lymphadenopathy (70%)
hoarseness or dysphagia (15%)
distant metastasis (5-10%)
What are the lab studies do you need to order for medullary thyroid carcinoma?
Serum calcitonin - likely to be elevated with palpable nodule
Fine-needle aspiration (FNA) biopsy
Genetic testing for RET gene mutation
PET scan if mets is suspected
all pts need to be tested for MEN2 genetic testing
For medullary thyroid carcinoma where do early mets metastasize to? What about late mets?
Early mets - cervical lymph nodes
Late mets - mediastinal nodes, lung, liver, trachea, adrenal, esophagus, and bone
What is the tx for medullary thyroid carcinoma?
Total thyroidectomy followed by lifetime supplemental thyroid hormone
______ should be offered to patients with (+)RET mutation without disease. _____ drug class needs to be avoided for medullary thyroid carcinoma
Prophylactic total thyroidectomy
Avoid GLP-1 drugs
Pheochromocytoma are bilateral in _____ of all MEN2 patients. _____ are bilateral in sporadic cases
60-80% of all MEN2 patients
10% are bilateral in sporadic cases
________ are needed at least 10-14 days prior to Pheochromocytoma removal sx.
alpha-blockers
What taking priority when thinking about order of removal for MEN2 related tumors?
**Pheo’s need to be removed prior to any other surgical procedures of MEN2 patients
high-arched palate
pectus excavatum
bilateral pes cavus
scoliosis
All s/s are associated with that type of MEN? What is the name?
MEN2B
Marfanoid habitus
What are some additional s/s associated with MEN2B?
Neuromas - growth of nerve tissue
affecting the eyelids, conjunctiva, nasal/laryngeal buccal mucosa, tongue, and lips
Hypertrophied lips
Intestinal autonomic ganglion dysfunction
How does Intestinal autonomic ganglion dysfunction present like? What MEN is it associated with? What are some common complications?
presents with a history of chronic constipation
MEN2B
complications of chronic constipation multiple diverticula and megacolon
Who needs to be screened for MEN2?
- All patients with MTC (despite family hx)
due to possibility of a de novo germline RET mutation
allows genetic testing for asymptomatic relatives - Patients with bilateral pheochromocytoma
- Patients with unilateral pheochromocytoma, particularly if this occurs with increased calcitonin levels
How is MEN4 inherited? What is the gene involved?
rare autosomal-dominant
cyclin-dependent kinase inhibitor gene (CDKN1B)
What tumors are MEN4 pts prone to?
3 Ps: Pancreas, parathyroid, anterior pituitary
______ are rare immune endocrinopathies characterized by the coexistence of at least two endocrine gland insufficiencies that are based on autoimmune mechanisms.
Autoimmune Polyendocrine Syndromes (APS)
What is APS type 1 known as? How common is it?
juvenile autoimmune polyendocrinopathy
VERY RARE only 500 cases reported in literature
How is APS type 1 inherited? What gene does it involve? What chromosome?
Autosomal recessive
mutations in the AIRE gene
found on chromosome 21
AIRE gene synthesizes a protein in the _____ called ______
thymus
autoimmune regulator
What is the job of the autoimmune regulator? What does a mutation of the AIRE gene lead to?
helps T-cells distinguish between self and foreign proteins and destroys autoimmune T-cells
Mutation of AIRE gene leads to and overproduction of autoimmune cells which attack the body’s tissue/organs
**What is the presentation of APS type 1?
Gonadal failure (MC - females)
Poor dentition - (hypoplasia of dental enamel)
DM-I
Thyroid disease
Alopecia, vitiligo
Intestinal malabsorption, pernicious anemia
Chronic hepatitis
Nail dystrophy
Debilitating diarrhea or obstipation
Are all part of the clinical presentation of _____.
How is the dx confirmed?
What antibodies will be present?
APS - Type I
Genetic analysis - AIRE gene mutations confirms diagnosis
Antibodies to anti-interferon alpha and omega can be identified in 100% of patients
What is the management of APS type 1? What are they at the highest risk for?
Team based approach with specialists
treat each individual dz
risk of acute addisonian crisis so need to address adrenal insufficiency first!!
What is APS type 2 a dysfunction of? What chromosome?
Dysfunction of human lymphocyte antigen (HLA) complex on chromosome 6
What is the function of the HLA gene?
HLA gene produces HLA proteins that reside on the surface of most all cells that allow the immune system to recognize the cell as “self”
What is the peak age of APS type 2? How common is it? More common in males or female?
Peak age of onset 20-60 years old
More common than APS-I affecting 1–2/100,000
More common in females with a 3:1 ratio
What is the etiology behind APS type 2?
unknown
Thought to be a combination of genetic and environmental factors
Strong family history of multiple autoimmune disorders
What is the clinical presentation of APS type 2?
How do you dx APS type 2? What is the monitoring involved?
Diagnosis of each individual condition is based upon typical clinical presentation and laboratory diagnostics
No specific genetic test to confirm dx
monitoring:
Every 1-3 years - screen for most common abnormalities
Comprehensive H&P
CBC, metabolic panel, TSH, and vitamin B12 levels
What is the management of APS type 2? What are they at the highest risk for?
team based approach
treat individual dz including hormone replacement if needed
acute addisonian crisis: must make sure pts are treated for this first!!!!
What are some differences bettwen APS type1 and APS type 2?
