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Flashcards in Neuroendocrine tumors Deck (57):

What are Neuroendocrine tumors (NET's)?

- neoplasms that arise from cells of the endocrine and nervous tissue:
rare, benign or malignant


Types of neuroendocrine tumors?

- MENs: type 1 and 2
- insulinomas (55%)
- gastrinomas (36%)
- VIPomas (5%)
- glucagonomas (3%)
- carcinoid


2 main categories of neuroendocrine tumors?

- well- differentiated
- undifferentiated (harder to tx)
- biologic behavior of these two entities differ remarkably, and the distinction is impt for planning therapy


When does the term MEN (multiple endocrine neoplasms) apply?

- applies specifically when 2 or more endocrine glands are affected


Characteristics of MEN syndromes?

- conditions which cause overactivity and enlargement and tumors of certain endocrine glands
- usually inherited conditions: autosomal dominant: each child has 50% chance of inheriting the gene
- families will have only one type of MEN, they are not at risk for developing another type of MEN


Diferent MEN syndromes?

- MEN 1: parathyroid tumors, pancreatic tumors, pituitary tumors (3 P's)
- MEN 2a: medullary thyroid cancers, pheochromocytoma, parathyroid
- MEN 2b: medullary thyroid cancers, pheochromocytoma, neuromas ****(no parathyroid)


What does MEN-1 involve?

- 3 P's: pituitary, pancreas, and parathyroid
- over-activity/tumors in different endocrine glands may occur simultaneously or at separate times


Who is affected by MEN 1?

- rare condition
- males and females are equally effected
- occurs in all major racial groups
- rarely happens before age of 10
- by 30, most people will have some type of endocrine gland over-activity, but sxs often don't develop until they are older than 30


What is the most common organ that is affected by MEN 1?

- almost all who inherit MEN 1 will develop over activity of parathyroid. (usually is the first clinical manifestation -.> hyperparathyroidism, bones, stones, moansm and groans)
- pancreas is next (75% of pts).
gastrin over-production common after 30 years of age (15% of pts), insulin over-production common under 30 you.
- pituitary adenoma occurs in about 15-20% of pts


Who should be tested for MEN 1?

- Not everyone with an endocrine gland problem should be tested
- people with over-activity of 2 or more of the glands involved in MEN should be examined for MEN 1
- MEN 1 usually doesn't cause cancer, typically benign tumors, pancreas will be most likely culprit of cancer


What are the tests for MEN 1?

- predictive genetic testing (chrom 11 q 13)
- regular screening for endocrine gland overactivity (family hx):
- calcium and PTH: yearly from age of 5
- prolactin
- gastrin


Tx for MEN 1?

- hyperparathyroidism: surgery
- pituitary adenomas:
dopamine agonist: cabergoline (1st choice), bromocriptine (2nd choice)
transsphenoidal surgery
- pancreatic/gastrointestinal tumors: proton pump inhibitor, or surgery


2 different categories of MEN?

- MEN 2a= medullary thyroid cancers, pheochromocytoma, parathyroid
- MEN 2b= medullary thyroid cancers, pheochromocytoma, neuromas


Manifestations of MEN 2a?

- thyroid
- adrenal: (adrenal medulla): pheochromocytomas
- hyperparathyroidism

very rare condition
1 in 20,000 will carry the gene
RET proto-oncogene x'some 10


With MEN 2A what are you likely to develop?

- will almost certainly develop medullary thyroid cancer
This is very aggressive, begins early in life and grows quickly, pts with MEN2 gene should have their thyroid surgically removed while they are young
- other diseases that may develop: cutaneous lichen amyloidosis and hirschsprung disease (this is absence of ganglion cells in the colon, no nerve cells to keep muscle of colon moving, so won't be able to have BM)


How do you test for MEN2a?

- predictive genetic testing - ret protooncogene mutation
- regular screening for endocrine activity: screening is aimed at detecting the earliest signs of Medullary cancer. This involves the pentagastrin test where admin. of pentagastrin causes raised levels of calcitonin within 2-3 minutes in affected individuals. This should be done in at risk pts yearly from age 15 to 35-50 years of age
- urinary catecholamin (adrenaline and noradrenaline)
- Ca or parathyroid levels should also be obtained every 2 years


What are the MEN 2b syndromes?

- medullary thyroid cancers
- pheochromocytomas
- mucosal neuromas
- marfanoid habitus


what are mucosal neuromas?

- small benign tumors of nervous tissue found in the mucosa of the body (linings of nasal sinuses, lips, tongues, respiratory tract, GI tract, biliary tract and pancreatic systems). Tx conservatively, removed only if they cause problems (by obstruction airways or passage of food


Characteristics of marfanoid habitus?

- MEN 2b
- arachnodactyly: long fingers and extremities
- tall with disproportionately long legs and arms - span of arms is greater than height,
- petus excavatum
- spinal abnormalities


How do you test for MEN 2b?

same as MEN 2a, except that screening for parathyroid abnormalities isn't done.
- predictive genetic testing - ret protooncogene mutation
- regular screening for endocrine activity: screening is aimed at detecting the earliest signs of Medullary cancer. This involves the pentagastrin test where admin. of pentagastrin causes raised levels of calcitonin within 2-3 minutes in affected individuals. This should be done in at risk pts yearly from age 15 to 35-50 years of age
- urinary catecholamin (adrenaline and noradrenaline)


Tx of MEN 2a and 2b?

- tx of 2a and 2b focuses on surgical removal of tumors that might spread to other parts of teh body or cause life-threatening biochemical disturbances
- with either syndrome, it may be necessary to perform opertations in stages to minimize the overall risk of complications
- if pheochromocytomas are present, they should be removed in a separate operation before proceeding with any other operations (can cause cardiac arrest)


How should confirmed medullary thyroid cancer be treated?

- with surgical removal of entire thyroid gland, followed by careful exploration and dissection of lymph nodes in the neck
- in most cases, it is recommended that lymph node dissection should be performed in the central compartment from the hyoid bone to the innominate veins and medial to jugular veins


What is insulinoma?

rare beta-cell tumor (in the islets of langerhans) that secretes insulin
- evenly distributed throughout the head, body and tail
- hyperinsulinemia: not responsive to falling glucose concentrations in the fasting state - result is persistent hypoglycemia
- more common in women (60%)
- median age at dx: 50
- 90% benign and solitary
- 10% are cancerous


Signs and symptoms of insulinoma?

- pts eat frequently to prevent hypoglycemia
- wt gain
- sxs typically begin with evidence of CNS lack of glucose:
blurred vision or diplopia, HA, slurred speech, weakness, anxiety or psychotic behavior, can have sweating and palpations, convulsions, coma (wehn hypoglycemia is severe)
- gradual process, slow onset
- takes 1-5 years for a dx


Why are the usual symptoms of hypoglycemia not too evident?

because of hypoglycemic unawareness


What is Whipple's triad of insulinoma?

- hx of hypoglycemia sxs
- associated fasting blood glucose of 45 mg/dL or less
- immediate recovery upon administration of glucose


Dx tests for insulinoma?

- tumors are generally small, hard to locate with CT, MRI
- 72 hr monitored fast: if glucose levels fall to less than 40 mg/dL while insulin levels are more than 20 U/mL
- insulin to glucose ratio is greater than 0.4 (normal:


- What other causes of hypoglycemia do you have to rule out before you dx insulinoma?

- reactive hypoglycemia
- adrenal insufficiency
- end-stage liver disease
- non-pancreatic tumors
- secretely admin. of oral hypoglycemics or insulin (metaformin)
- after confirmation: CT or MRI -> look for metastasis


How can you localize the insulinoma before surgery?

- transabdominal ultrasound and CT are preferred initial tests. Followed by endoscopic ultrasound
- last resort: arterial stimulation with hepatic venous sampling when an insulinoma hasn't been localized by noninvasive techniques


Tx of insulinoma?

- surgical resection of pancreas
- meds: diazoxide (inhibits insulin secretion)
octreotide: inhibits secretion of many hormones such as gastrin, CCK, glucagon, insulin, secretin, pancreatic polypeptide, reduces secretion of fluids by intestine and pancreas. Also reduces GI motility and inhibits contraction of the gall bladder
- it inhibits the secretion of certain hormones from the anterior pituitary

- continuous SQ glucagon infusion to prevent hypoglycemia
- malignant insulinoma - streptozotocin


Surgical tx of an insulinoma?

- resection of peripancreatic and duodenal nodes is advised in pts with probably malignant tumors
- surgical resection is curative in about 95% of cases
- malignant insulinomas recur in about 33% of cases


What is gastrinoma zollinger-ellison syndrome?

- tumor of pancreas or duodenum
- produces excess levels of gastrin: gastrin stimulates gastric acid and pepsin production
- 25% are part of MEN-1 syndrome
- most pts dx b/t ages 20-50
- incidence is higher in men
- classified: well differentiated or poorly differentiated


How are gastrinoma zollinger-ellison syndrome classified?

- well differentiated
- poorly differentiated


What occurs when tumor acts on gastrin cells?

going to have high gastric output


sxs of gastrinoma zollinger-ellison syndrome?

- frequent peptic ulcers with absence of h-pylori or NSAID consumption
- duodenojejunitis
- esophagitis
- refractory diarrhea - due to pH levels
- multiple duodenal ulcers
- in severe cases: rupture, bleeding, intestinal obstruction


Dx of Gastrinoma zollinger-ellison syndrome?
- test protocol?

- fasting gastrin, look for results to be >1000 with ZES (this is dx)
- test protocol: don't eat for 12 hours before test, don't drink alochol for 24 hours before the test, water can be consumed without limitation up to 1 hour before test, don't chew gum or smoke cigs for 4 hours before the test (gum creats gastric acid)
- acid reducing meds or proton pump inhibitors should be temporarily stopped before this test. Tums and rolaids need to be stopped the night before the test
- stress can affect gastrin levels, so you may be asked to rest quietly for 30 minutes before the blood sample is drawn (normal gastrin is around 100, ZES pts will have >1000 levels)


Tests for gastrinoma ZES?

- if gastrin >200 and


Results of dx testing of secretin provacation test?

- normally, see no change or a slighlt suppression of gastrin concentration
- pts with gastronome demonstrate a paradoxical increase of 100-200 pg/mL. Approx 90% of pts with gastrinoma will have positive secretin test


What is Somatostatin receptor scintigraphy?

- a type of radionuclide scan used to find carcinoid and other types of tumors. In SRS, radioactive octreotide, a drug similar to somatostatin, is injected into the vein and travels through the bloodstream. The radioactive octreotide attaches to tumor cells that have receptors for somatostatin. A radiation measuring device detects the radioactive octreotide, and makes pictures showing where the tumor cells are in the body. The procedure is also called an octreotide scan (full body scan looking for a tumor)


What is the gastrinoma triangle?

- Where 90% of gastrinomas are located (50% duodenum and 50% pancreas), in head of pancreas and duodenum.


Tx of Gastrinoma ZES?

tx: control gastric hypersecretion -> high doses of proton pump inhibitors
- surgical removal of gastrinoma


Why sould pts that meet criteria for operability undergo exploration for possible removaal of the gastrinoma tumor?

- because 50% of gastrinomas metastasize to lymph nodes of the liver, and are therefore considered malignant
- surgery: excision of duodenal wall is performed if a duodenal gastrinoma is found. All lymph nodes in the gastrinoma triangle are excised for pathologic analysis
- if the gastrinoma is found in the pancreas and doesn't involve the main pancreatic duct, it is enucleated.


What is a VIPoma also known as?

Verner-Morrison syndrome


What is a VIPoma?

- pancreatic neoplasm secreting vasoactive intestinal polypeptide (VIP)
- affects the tail of the pancreas
- dx b/t 30-50 yoa


Physiology of VIP?

- it helps control and send nerve signals
- it helps relax certain muscles along the GI tract
- it increases the amt of water and electrolytes released from the pancreas and gut
- it triggers the release of hormones from the pancreas, gut and hypothalamus
- it helps break down fat and glycogen
- it stimulates bile flow
- it blocks gastrin and gastric acid release


What is the classical cinlical syndrome of VIPoma?

- severe, intermittent, watery diarrhea:
dehydration, weakness from electrolyte losses
decrease gastrin production, and large amounts of K+ are lost in the stool, will be very flushed, will have muscle weakness, lethargic


VIPoma dx?

- labs: serum VIP levels >75 pg/mL

imaging: ultrasound


VIPoma tx?

- fluid loss and correction: electrolyte and fluid balance is sometimes difficult to correct peoperatively and must be pursued aggressively
- somatostatin analogs are helpful in controlling the diarrhea and allowing replacement of fluid and electrolytes: octreotide or lanreotide

Surgical resection: usually in distal pancreas, or palliative care if cancer too far gone



- pancreatic islet cell tumor that secretes glucagon
- increases levels of glucose in the blood
- produces a distinctive rash
- 80% are cancerous
- grow slowly
- 80% women


Sxs of glucagonoma?

- those of DM 1: wt loss and hyperglycemia
- necrolytic migratory erythema: begins as erythematous papules or plaques involving the face, perineum, and extremities
- over 7-14 days the lesions enlarge and coalesce. Central clearing then occurs, leaving bronze-colored, indurated areas centrally, with blistering, crusting and scaling at the borders
- the affected areas are often pruritic and painful


Dx of glucagonoma?

- serum glucagon level> 500 pg/ml (norm 50-200)
- imaging to ID tumor location: MRI or CT


Tx of glucagonoma?

pancreatic resection (distal)
- zinc ointment for skin rash

surgery: often in body or tail of pancreas, tend to be large tumors with metastases. Debulking operations are recommended in good operative candidates to relieve symptoms


Carcinoid tumor characteristics?

- 1.5 cases/100 k
- most are slow growth w/o sxs
- sxs from tumors in ileum and jejunum

- have: tumor in foregut, midgut, hind gut or MEN type 1


Where are the most common carcinoid tumors in the midgut?

ileum, jejunum, right colon, and appendix

- pathophys: 40 secretory products - serotonin, histamine, tachykinins, and prostaglandins


Signs and Sxs of carcinoid tumors?

- periodic abdominal pain -> blockage of tumor in the small bowel:
wll have flushing thats episodic, induced by exercise, stress, certain foods, increased duration
- diarrhea, malabsorption
- wheezing and dyspnea


Dx in carcinoid tumors?

- imaging: radiography (upper and lower GI series w/ contrast), CT, octreoscan, MRI
- colonoscopy
- histology


management of carcinoid tumors?

- surgically:
appendectomy, block resection with adjacent lymph nodes

- medically: reduction - chemo (numerous meds used and in combo)

- palliative: octreotide

- prognosis is excellent to poor (if gets to lymph nodes)