Islet Cell Tumors and MEN Syndromes (Nichols) Flashcards
the most common type of pancreatic neuroendocrine tumor to produce an endocrine syndrome is a tumor making ….manifested by ….
insulin with hypoglycemia
What are the symptoms of hypoglycemia
shaky, sweaty, nervous, hunger, weak, visual disturbances, palpitations
most common visual dist seen w/ hypoglycemia
blurred vision
Why don’t you get a history of an episode of hypoglycemia from the pt?
many of these episodes are assc with amnesia ∴ ask family and friends
signs of hypoplgycemia
diaphoresis, tachycardia, systolic hypertension, tremulousness, pallor, confusion, unusual behavior
what are the body’s defenses against hypoglycemia
at glc below 80…↓ insulin
at glc below 70… ↑glucagon, epi, and cortisol
At what blood glc level do symptoms of hypoglycemia manifest (
below 50
how does fibrosis and amyloid impair the body’s defenses against hypoglycemia
disrupts intra-islet signaling (via insulin) that would cause the pancreas to ↑glucagon secretion
previous episodes of hypoglycemia impair the body’s defenses against hypoglycemia by …
lowing the threshold for sympathoadrenal response ∴ glc must fall even lower for epi and cortisol to be released
alcohol impairs hepatic (gluconeogeneis or glycogenolysis)
gluconeogenesis
in terms of hypoglycemia, what is the effect of a 1 day vs 2 day vs 3 day binge drinking event without eating
(duh, why waste space in your stomach with mac n cheese when you can polish off that 4th bottle of vodka?!?!–sidebar, how many bottles of vodka could one conceivably finish in a 3 day prd… i couldn’t decide on a good number, 1/day didn’t sound like enough but 5 seemed excessive? so I settled on 4. Aaand I just rewrote the broken-adult version of goldilocks and the 3 bears… anyway, back to science…)
1 day is unlikely to cause hypoglycemia due to liver glycogen stores (glycogenoslysis is fine) but around day 2 or 3, you run out of glycogen stores. Since the alcohol inhibits gluconeogenesis, the pt will become hypoglycemic!
serious consequences of hypoglycemia
seizures, arrhythmias, and DEATH (muahahaha)
I think Nichols is rubbing off on me… im including colorful writing in my notes…
please don’t tell anyone
(Better or worse) control of blood sugar leads to more episodes of hypoglycemia
better/tighter
when are insulin dept diabetic pts more prone to attacks of hypoglycemia
during sleep
What are additional factors that can contribute the the development of hypoglyemia
renal failure (↓Cx insulin)
missed meals
weight loss
exercise
the cycle of recurrent iatrogenic hypoglycemia can be reversed in ____ weeks of …
2 weeks of careful avoidance of hypoglycemia
what do you give all comatose pts
glucose
Most NETs are (functional or non-functional)
non-functional
____ is elevated in 70% of NETs
serum chromogranin A
80-100% of pts with MEN-1 will develop…
pancreatic NET with endocrinopathy?
i couldn’t decide what he meant by “one” on that slide, pg. 5
salt and pepper chromatin arranged in nests or trabeculae
histo of pancreatic NETs, especially islet cells
T or F: malignant vs benign pancreatic NETs are easily differentiated under the microscope
F: they look the same
What are the most common sites of metastases for pancreatic NETs
liver > retroperitoneal LN > bone
grossly, how can you tell if a tumor is benign or malignant
look to see if it is invading nearly organs/tissue
most common presentation of a non-functional pancreatic NET
asymptomatic
some abd pan, obstructive jaundice, anorexia/nausea, palpable mass
What are 5 pancreatic NETs discussed (ID 2 most common)
- insulinoma
- gastrinomas
somatostatinoma
glucagonoma
VIPoma
episodic hypoglycemia
insulinoma
insulinomas are generally (aggressive or indolent)
indolent (87% are single benign tumors)
histo of insulinoma:
trabeculae + immunostain for insulin
causes Zollinger-Ellison Syndrome
gastrinomas
What is Zollinger-Ellison Syndrome
unrelenting PUD w/ abd pain and diarrhea
Can gastrinomas appear outside the pancreas?
yes, 40% do
DM, painful glottis, inflammed lip (cheilitis),
+ weight loss, GI dist, normocytic anemia, thromboembolism, neurophychiatric dist,
glucagonoma
erythematous, painful, puritic rash that begins as macules which coalesce, develop central bullae and then erode (leaving hyperpigmentation, and crusting at periph)
Necrolytic Migratory Erythema
describe the spread of Necrolytic Migratory Erythema
perirectum → perineum, thighs, butt, legs
Necrolytic Migratory Erythema is assc with what pancreatic NET
glucagonoma
*but is not specific to glucagonoma
Assc with DM and weight loss
glucagonoma
Why are glucagonomas assc with DM and weight loss
glucagon opposes the action of insulin (~resistance)
and it is lipolytic
use of glucagon in ER
resuscitation of hypoglycemic pt when there is no vascular access
overdose of BB and CCB
*Glucagon activates adenyl cyclase and exerts an inotropic and chronotropic effect (↑cAMP) by a pathway that bypasses the b receptors
if glucagon fails to reverse BB and CCB OD, what can be used
insulin + glc
DM + Cholelithiasis + steatorrhea
somatostatinoma syndrome (this seen in only 10% of somatostatinoma cases…)
explain pathyphys behind the sydrome assc with somatostatinoma syndrome
- DM: stomatostatin ↓insulin release
- Cholelithiasis: stomatostatin ↓cholecystokinin release → ↓gallbladder emptying
- steatorrhea: inhibits pancreatic sectrion and lipid absorption
treatment forpancreatic NETs
- surgical resection
- sunitinib and everolimus if unresectable
- octreotide to control symptoms if unresectable
parathyroid, pancreas, pituitary
MEN-1:
hypoglycemia hypoglycemia hypoglycemia
insulinoma
severe watery diarrhea, achlorydria, hypokalemia, acidosis
VIPoma
PUD, diarrhea
gastrinoma
*Zollinger-Ellison Syndrome
3 words to remember for…
tumor secreting vasoactive intestinal peptide
VIPoma
DM, cholelitiasis, steatorrhea
somatostatinoma
pancreatic cholera
verner-morrison syndrome
VIPomas
most common symptoms of somatostatinomas
abd pain and weight loss
thyroid medullary, pheocromocytoma
MEN-2
necrolytic migratory erythema
glucagonoma
watery diarrhea, achlorhydria
VIPoma
DM, painful glottis, inflammed lip (cheilitis),
glucagonoma
serum chromogranin A
pancreatic NETs
DM and weight loss
glucagonoma
how can MEN cause hyperCa?
MEN is a parathyroid adenoma causing hyper PTH which ↑Ca CHRONICALLY
urinary pain + endocrinopathy think…
chronic Ca elevation
*if fever, UTI
epidemiolgy for primary hyperPTH
inc incidence with age
women > men
blacks and asians
hypercalcemia + bilateral hilar lymphadenopathy + non-caseating granulomas
sarcoid
why can sarcoid present with hyperCa?
macrophages in granulomas convert vitD to mature form (NO FEEDBACK REG) → ↑bone resorption → ↑Ca
**only 20% of sarcoid pts have hyperCa
can mimic islet cell tumor or MEN
paraneoplastic syndrome
most common paraneoplastic syndrome
hyper Ca
Acute vs chronic hyperCa presentation
chronic: mostly asymptomatic, maybe mild anxiety, depression or cognitive difficulties
acute:
muscle weakness, ↓muscle reflexes,
confusion, lethargy → seizure → coma → death
constipation → nausea and vomiting
polyuria and polydipsia (interfere with ADH)
shortened OT and bradycardia
asymptomatic and primary hyperPTH
chronic hyperCa
confusion, lethargy, obtundation, and paraneoplastic
acute hyperCa
amenorrhea and galactorrhea
prolactinoma
prolactinoma is the most common …
pituitary adenoma
lactation failure, amenorrhea, asthenia, apparent pre-mature aging, dryness and hypopigmentation of skin, genital and axillary hair loss
*post-partum
sheehan syndome
what is the predomidant manifestation of acute adrenal insufficiency?
shock
*+nonspecific symptoms, weight loss, fatigue, nausea, vom, abd pain, weak, fatigue, fever, confusion
CANNOT HANDLE STRESSES TO BODY
what color are adrenal cortical tumors? why?
yellow/gold
Cortisol/cholesterol
postpartum hypopit due to necrosis of the gland from peripartum hemorrhagic shock
sheehan syndrome
hypertension and hypokalemia
Conn syndrome seen in aldosterone secreting adrenal cortical tumors
majority of adrenal cortical tumors are (functional or non-functional)
nonfunctional
catecholamine secreting tumor of the adrenal medulla
pheochromocytoma
what are 2 substances adrenal cortical tumors can secrete
cortisol and aldosterone
HTN, episodic headaches, sweating, tachycardia
pheochromocytoma
A 35-year-old black female presents with the acute onset of painful urination associated with increased urination, constipation, anorexia, fatigue, depressed mood and confusion. She most likely has…
hypercalcemia
symptoms of acute hyperCa and hypoCa
Hyper: Stones, (abdominal) Moans, (psychic), Groans, Bones, constipation
hypo:parasthesias (esp lips), muscle cramps, irritability, depression
symptoms of acute hyperglycemia and hypoclycemia
hyper: polyuria, polydipsia,polyphagia, fatigue, weight loss
Hypoglycemia: shakiness, sweatiness,nervousness, hunger, weakness
symptoms of acute hyperK and hypoK
Hyperkalemia: fatigue, weakness, nausea,
parathesias, confusion
Hypokalemia: fatigue, weakness, constipation,
irritability, myalgias
symptoms of acute hyperNa and hypoNa
Hypernatremia: lethargy, confusion,
irritability, seizures, coma
Hyponatremia: lethargy, confusion,
irritability, seizures, coma*
Urolithiasis is suggestive of (acute or chronic) hypercalcemia
chronic
what makes an presentation of hypercalcemia more severe?
↑# symptoms and more severe neurological impariment
how can you differentiates parathyroid adenoma from hyperplasia
hyperplasia is in more than one glad
adenomas are uni-focal
pre-mature menopause in a person wil DM for 15+ years
accelerated aging
tumors of parathyroid, pancreas, pituitary
MEN-1
