Pathology - Nichols II Flashcards
Pancreatic Neuroendocrine Tumor
-most common to produce an endocrine syndrome is a tumor making insulin (hypoglycemia)
NETs
rare
middle-aged
sporadic
~75% non-functioining
-Serum chromogranin A is elevated in about 70%
of patients with pancreatic NETs (functioning
and non-functioning), but specificity is poor
-Some associated with hereditary
endocrinopathies:
80-100% of patients with MEN-1 will develop one,
along with up to 20% of patients with von Hippel Lindau syndrome,10% of patients with neurofibromatosis-1 and 1% of patients with tuberous sclerosis.
Symptoms of Hypoglycemia
1) Shakiness
2) Sweatiness
3) Nervousness
4) Hunger
5) Weakness (muscle)
6) Visual Disturbances
7) Palpitations
Most common visual disturbance in Hypoglycemia?
-blurred vision
Other symptoms of Hypoglycemia?
- becoming quite/catatonic (unresponsive to verbal stimuli)
- agitated/hot tempered
- amnesia of episodes of hypoglycemia (like patients on benzodiazepines or petit mal seizures) so history will be false negative
- ask family/friends about episodes of what might be Hypoglycemia
Signs of Hypoglycemia?
1) Diaphoresis
2) Tachycarida
3) Systolic Hypertension
4) Tremulousness
5) Pallor
6) Confusion
7) Unusual Behavior
1-5 indirect dep. on sympathoadrenal response to hypoglycemia
Bodies defense against Hypoglycemia
1) decreased insulin (glucose < 80)
2) increased glucagon (glucose < 70)
3) increased epi (glucose < 70 not super helpful)
5) symptoms (glucose < 50)
Hypoglycemia-associated Autonomic Failure
1) exogenous insulin obliterates the body’s first defense
2) Islet fibrosis or amyloid impairs impairs the body’s second defense because intra-islet insulin is the signal for increased glucagon
3) Previous episodes of hypoglycemia itself lower
the threshold for this part of the sympatho-
adrenal response, the third defense
Alcohol and Hypoglycemia
-alcohol does not impair hepatic glycogenolysis, but liver glycogen stores average only 8 hours, and alcohol does impair hepatic gluconeogenesis, so a one-day binge of drinking without eating is unlikely to cause hypoglycemia, but a 2-day binge more likely & a 3-day binge even more likely to cause hypoglycemia
Can hypoglycemia cause death?
yes, seizures, cardiac arrhythmias
3-4% or deaths in insulin-treated diabetics
Insuline Therapy
- want to prevent hypoglycemia, but achieving tighter control of blood sugar leads to more episodes especially during sleep
- Factors: missed meals, exercise, weight loss, renal failure (renal failure causes decreased insulin clearance
- vicious cycle of recurrent iatrogenic hypoglycemia is reversible by as little as 2 weeks os scrupulous avoidance of hypoglycemia
What to give to comatose patient?
glucose
Neuroendocrine Tumors in General
Islet Cell Tumors specifically…
-composed of 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 (cords),
strands, islands, glands or sheets
[this is the architecture].
Malignant Pancreatic Neuroendocrine Tumors
-look very much, often just like
benign ones under the microscope,
even metastases
Most common site of Metastases in Malignant Pancreatic Neuroendocrine Tumors?
1) liver
2) retroperitoneal lymph nodes
3) bone
Symptoms of Pancreatic Neuroendocrine Tumors
-many are asymptomatic
abdominal pain (up to 78%) obstructive jaundice (up to 50%) anorexia / nausea (45%) palpable mass (up to 40%) weight loss (up to 35%) intra-abdominal bleed (up to 20%)
Insulinomas
-Most common type of pancreatic neuroendocrine tumor (1,200/yr) Generally indolent tumors -87% single benign tumors -7% multiple benign tumors -6% malignant -8% part of MEN1 syndrome (type 1 multiple endocrine neoplasia)
Insulinoma Syndrome
Episodic hypoglycemia
with confusion, visual disturbances, unusual behavior, tremulousness, palpitations and diaphoresis.
What stain to see insulin?
immunostain
Gastrinomas
-2nd most common type of pancreatic neuroendocrine tumor
-cause Zollinger-Ellison syndrome:
unrelenting peptic ulcer disease,
abdominal pain (90%)
diarrhea (50%)
-40% occur outside the pancreas
-25% part of MEN1 syndrome
Glucagonoma
-ultra-rare (30 per year)
Glucagonoma Syndrome:
Diabetes mellitus, Painful glossitis (tongue inflammation), Cheilitis (lip inflammation), Normocytic anemia, Gastrointestinal disturbances, Neuropsychiatric disturbances, Thromboembolism, Weight loss and Necrolytic Migratory Erythema
Necrolytic Migratory Erythema
- 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.
- can also occur in other diseases
Why would a glucagonoma
cause diabetes mellitus?
Because it opposes the action of
insulin.
Why would a glucagonoma
cause weight loss?
Because it is catabolic (lipolytic).
