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)