Clinical App: Islet Cell Tumors and MEN syndromes` Flashcards
The most common type of pancreatic neuro-endocrine tumor to produce an endocrine syndrome is a tumor that makes ________, resulting in what clinical manifestation?
Insulin; hypoglycemia
Symptoms of hypoglycemia (7 of them)
- Shakiness
- Sweatiness
- Nervousness
- Hunger
- Weakness
- Visual distubances- blurred most commonly
- Palpitations
How should you avoid getting a false negative history of episodes of hypoglycemia?
Ask family or friends about what might hypoglycemia. Pt themselves may have episodes of amnesia
Signs of Hypoglycemia (7 of them). Which are dependent of sympathoadrenal response?
- Diaphoresis
- Tachycardia
- Systolic hypertension
- Tremulousness
- Pallor
- Confusion
- Unusual behavior
1-5 are indirect manifestations dependent on sympathoadrenal response to hypoglycemia
What are the body’s defense mechanisms against hypoglycemia? (5, from most to least important)
- Decrease insulin (when glucose is <80)
2) increased glucagon (normally kicks in
when glucose drops below 70 or so)
3) increased epinephrine (normally kicks in
when glucose drops below 70 or so)
4) increased cortisol (normally kicks in when glucose drops below 70 or so, but not rapidly helpful)
5) symptoms (normally occur when glucose drops below 50 or so)
What are the hypoglycemia-associated autonomic failures that can occur at each of the 5 defense mechanisms against hypoglycemia?
- Exogenous insulin (decrease production of insulin)
- Islet fibrosis or amyloid impairs the body’s
second defense because intra-islet insulin
is the signal for increased glucagon
3-5: Previous episodes of hypoglycemia lower the threshold for (increased epi, cortisol, symptoms) of the sympathoadrenal response.
T or F. Alcohol impairs hepatic glycongenolysis.
F. Alcohol impairs hepatic gluconeogenesis
How can alcohol lead to hypoglycema?
Liver glycogen stores only 8 hours and alcohol impairs hepatic gluconeogenesis. 2-3 day binge where you plow through your glycogen stores and are too drunk to remember to eat.
_____ can cause seizures, cardiac arrythmias, and 3-4% of death in insulin-treated diabetics.
Hypoglycemia
What does renal failure do to insulin clearance?
Decreases it– increase risk of hypoglycemia
The vicious cycle of recurrent iatrogenic hypoglycemia is reversible by ____
as little as 2 weeks of scrupulous avoidance of hypoglycemia
Epidemiology of NETs
Rare, middle-aged pt, sporadic
Are most NETs functioning or non-functioning?
Most, up to 75%, are non-functioning–> which means there is no associated hormone syndrome
______ is elevated in about 70% of pt with pancreatic NETs, but specificity is poor.
Serum chromogranin A
Some NETs are associated with hereditary endocrinopathies. ____% of MEN1 pt will develop one, ___% of von Hippel Lindau syndrome will
80-100% of MEN1
20% of vHL
10% of nf1
1% of ts
What is tuberous sclerosis?#
AD disorder diagnosed in children that manifests with cortical tubers, hamartomas, hypo-pigmented “ash-leaf” skin lesion, renal angiomyolipomas, cardiac rhabdomyomas(which is the most common primary cardiac tumor in children)
What do neuroendorcrine tumors and islet cell tumors generally look like histologically?
small, bland, uniform, monotonous, benign-looking cells with round-to-oval nuclei with inconspicuous nucleoli and a stippled chromatin pattern sometimes called “salt and pepper” and scant pink eosinophilic granular cytoplasm (minimal mitoses, pleomorphism, anaplasia, desmoplasia, or necrosis) arranged in nests, trabeculae, strands, islands, glands or sheets
What are the common sites of metastases of pancreatic NETs?
liver, retroperitoneal lymph nodes, bones
Are all NETs malignant?
No- but malignant and benign look identical-ish histologically
Symptoms of non-functioning pancreatic NETs
Many are ASYMPTOMATIC and and disovered on imaging. Others (most to least common)
Abdominal pain, anorexia/nausea, palpable mass, weight loss, intra-abdominal bleed
____ is the most common type of functioning pancreatic NET.
Insulinomas
Are insulinomas indolent/rapid growing? Single/multiple?
Generally indolent. 87% are single benign, 7% are multiple benign, 6% are malignant. 8% are part of MEN1 (remember 3 Ps for pancreas, pituitary, parathyroid)
Someone comes with hypoglycemia and you suspect an insulinoma. What other causes of hypoglycemia should you rule out?#
exogenous insulin, alcoholism, adrenal insufficiency, liver failure, hypopituitarism, sepsis, glucagon deficiency
How do insulinomas present?
epidoside hypoglycemia–> confusion, visual disturbances, unusual behavior, tremulousness, palpitations, diaphoresis.
(same thing different wording): Whipple triad: 1. Fasting hypoglycemia 2. Symptoms of hypoglycemia 3. relief of symptoms after IV glucose
Insulinomas are often associated with _____ symdrome
MEN1 (3 Ps! Pancrease, pituitary, parathyroid)
_____ is the 2nd most common type of functioning pNET.
Gastrinoma
Describe gastrinoma (what do they cause, what are they associated with)
Zollinger-Ellison syndrome: unrelenting peptic ulcer disease, abdominal pain, diarrhea.
40% occur outside pancreas
25% part of MEN1
How common is glucagonoma?
ultra-rare (30 per year)
What is included in glucagonoma?
Diabetes mellitus, painful glossitis, cheilitis, normocytic anemia, GI disturbances, neuropsychiatric disturbances, thromboembolism, weight loss, and…..necrolytic migratory erythema (bolded in first aid… must be important)
Please describe necrolytic migratory erythema with colorful adjectives.
Erythematous, painful, pruritic rash begins as macules which coalesce and develop central bullae, then erode, leaving HYPERpigmentation and crusting of the periphery. Usually begins in the perirectal area with subsequent spread to the perineum, thighs, buttocks, and legs.
Does necrolytic migratory erythema= glucagonoma?
No
Why would glucagonoma cause DM?
because it opposes action of insulin
Why would glucagonoma cause weight loss?
it is catabolic– lipolytic
How do you diagnose glucagonoma?#
Glucose levels not suppressed by glucagonoma
Describe how glucagon is used in the ER
- resuscitation of comatose patients with hypoglycemia if there is no vascular access.
- first line therapy for treating overdoses of beta-blockers and is also used for overdoses of calcium channel blockers.
- High dose insulin and glucose can be tried
if glucagon fails to adequately reverse the manifestations of beta blocker or calcium
channel blocker overdose.
How common is somatostatinoma?
Ultra rare….30 a year in US
What 3 things are included in somatostatinoma syndrome?
- DM
- Cholelithiasis (gallstones)
- Steatorrhea (smelly greasy diarrhea due to fat malabsorption)
How does somatostatin cause DM in somatostatinoma syndrome?
It inhibits release of insulin from B cells
How does somatostatin cause cholelithiasis in somatostatinoma syndrome?
inhibits cholecystokinin release and hence gallbladder emptying
How does somatostatin cause steatorrhea in somatostatinoma syndrome?
inhibits pancreatic secretion and lipid absorption
What are the 2 most common symptoms of somatinostoma?
abdominal pain and weight loss`
How common is VIPoma?
30 per year
What is VIPoma?
: VIP= vasoactive intestinal peptide which is increased
Verner-Morrison syndrome, pancreatic cholera
Watery diarrhea, hypokalemia, achlorhydria, severe diarrhea, hypovolemia, acidosis.
How do you diagnose VIPoma?#
Clinical…..this is bolded in first aid
So you would look for watery diarrhea, hypokalemia, and achlorhydria
Imaging studies for the Dx of pNETs
CT and MRI both work. Endoscopic ultrasound works well: 82% sensitivity, 95% specificity Somatostatin receptor scintigraphy (imaging with a radiolabeled somatostatin analogue) works well
Tx and prognosis of pNETs
Surgical resection (unresectable: octreotide, kinase, mTOR inhibitors) Variable: with MEN have more indolent course
MEN 1: Tumors of what? How could they present? #
Pancreas, pituitary, parathyroid…..kidney stones thanks to hyperparathyroid, GI ulcers thanks to gastrinoma (Zollinger-Ellison)
MEN 2: Tumors of what?
:
medullary thryoid carcinoma, pheochromocytoms anndddd
2A: parathyroid adenoma
2B: ganglioneuromatosis
90% of chronic hypercalcemia is due to _______. 85% of that is due to ________. 10% of that is due to _______.
Hypercalcemia—> primary hyperPT—> parathyroid adenoma—> MEN
Causes for hypercalcemia#
MISHAP
Malignancy, intox with VD, Sarcoidosis, hyperparathyroidism, Alkali, Pagets
Also renal osteodystrophy, familial hypocalciuric hypercalcemia, and thiazide diuretics
Symptoms of chronic hypercalcemia
: Stones, bones, groans, and psychiatric overtones
none?
vague mild anxiety, depression, cognitive difficulties, constipation, kidney stones, bone pain due to resorptive disease (osteitis fibrosa cystica)
Symptoms of hypercalcemic crisis#
polyuria, dehydration, mental status changes
Epidemiology of primary hyperparathyroidism
Common, increasing incidence with age, 2.5x more common in women, 50% more common in AA and Asians
What is the difference between fat in normal PT and PT adenoma?
There is very little/no fat in adenoma where normal PT has fat in it
Describe how sarcoidosis and chronic hypercalcemia are related
Macrophages in granulomas convert VD to its mature form withoutf feedback inhibition—> hypercalcemia. Only 10-20% of sarcoidosis pt have hypercalcemia
_____ is the most common paraneoplastic syndrome.
Hypercalcemia
How does acute hypercalcemia present?
A. Most of the manifestations involve the musculoskeletal or nervous systems and include muscle weakness, decreased muscle reflexes, confusion and disorientation, followed by progressive lethargy culminating in seizures,
coma and death.
B. gastrointestinal system: constipation, followed by progressive nausea and vomiting.
C. Patients may have polyuria and polydipsia due to interference with the function of antidiuretic hormone.
D. Shortened QT interval and bradycardia
If you see confusion, lethargy, obtundation, and paraneoplastic syndrome think ______.
If you see asymptomatic and primary hyperparathyroidism think _____.
Acute hyperCa……Chronic hyperCa
_____ is the most common type of pituitary adenoma.
Prolactinoma
this is most common FUNCTIONING…..Most common pituitary tumor overall is nonfunctioning adenoma
Epidemiology of prolactinoma
Females, middle aged, but a few could be part of MEN 1 (3 Ps)
Symptoms of prolactinoma
amenorrhea, galactorrhea
#: in addition, infertility, decreased libido and osteopenia, In men impotence and gynecomastia. Bitemporal hemianopsia
Differential for prolactinoma#
Dopamine problem
Drugs (reserpine, methyldopa, antipsychotics)
Hypothyroidism (elevated TRH–> increased Prl secretion)
What is sheehan syndrome?
postpartum hypopituitarism due to necrosis of the gland from peripartum hemorrhagic shock. Rare.
Symptoms of sheehan syndrome?
Lactation failure, amenorrhea, asthenia, premature aging, dryness and hypopigmentation of skin, genital and axillary hair loss
Describe acute adrenal insufficiency
predominant manifestation of adrenal crisis is shock, but patients often have nonspecific symptoms such as anorexia, nausea, vomiting, abdominal pain, weakness, fatigue, lethargy, fever, confusion or coma.
Hypoglycemia is a rare
Describe chronic adrenal insufficiency
fatigue, malaise, anorexia, nausea, abdominal pain, diarrhea, weight loss, weakness, salt craving, hypotension, impaired memory, depression, psychosis, hyperpigmented skin, hyponatremia, hyperkalemia, loss of libido and genital hair (females), and hypoglycemia (in type 1 diabetics).
Stress is mediated by ______ and causes ______.
Acute: catecholamines
Chronic: corticosteroid hormones
Tachycardia, hypertension, hyperventilation, hyperglycemia
Describe the majority of adrenal cortical tumors.
incidentalomas,non-functioning adenomas
discovered on imaging (4% of high resolution imaging)
A few adrenal cortical tumors secrete cortisol causing ______ or aldosterone causing ______.
Cortisol: Cushings
Aldo: HTN, hypoK, Conn syndrome
____ is a catecholamine secreting tumor of the adrenal medulla.
Pheochromocytoma
Epidemiology of pheochromocytoma
rare, up to 20% in pt with MEN2 or von hippel lindau. Middle age.
Signs and symptoms of pheochromocytoma
: Episodic everything: HTN, palpitations, anxiety, weight loss, headaches
Symptoms: Triad of episodic headache, sweating, tachycardia (usually dont have all 3)
Signs: HTN (+/- paroxysmal)
Gross appearance of pheochromocytoma
gray, pink, or red (hemorrhage)
