2-6: 5/12: Pheochromocytoma And Neuroendocrine Tumor Syndromes

Front 1

Pheochromocytomas:
What are they?
Cause

Back 1

Cathecholamine producing tumors
Arise from chromaffin cells of adrenal medulla or extra-adrenal paraganglia

Most are adrenal in origin!
adrenal origin = pheo
extra-adrenal pheo = paraganglioma (15-20%)

Cause:
Sporadic
Hereditary Syndromes

Front 2

Multiple Endocrine Neoplasia Type 2 is associated with ________ which results in _______.

Back 2

RET proto-oncogene mutation, tyrosine kinase constantly active

Front 3

MEN Type 2A vs 2B

Back 3

2A: Medullary thyroid ca, pheochromocytoma, hyperpara

2B: medullary thyroid ca, pheochromocytoma, Marfanoid habitus, multiple neuromas

Front 4

Von Hippel-Lindau syndrome
What cancers is it associated with?

Back 4

Mutation in VLH tumor suppressor gene leads to pheo (addnly: RCC, retinal and CNS hemangioblastomas)

Front 5

Neurofibromatosis type 1

Back 5

Mutation of NF1 (tumor suppressor gene), manifests as cafe au lait spots, multiple fibromas on skin; only 5% have pheo

Front 6

Familial paraganglioma

Back 6

Mutation in succinate dehydrogenase enzyme complex (mitochondrial complex II) activates tumor-promoting genes

Manifestations: adrenal pheochromo, extra-adrenal pheo (paraganglioma), head and neck paraganglioma

Front 7

What is the rule of 10?

Back 7

Sporadic pheos follow rule of 10:
10% hereditary
10% bilateral
10% extra-adrenal
10% malignant

BUT IT'S NOT TRUE

Front 8

Triad of pheo symptoms.

Other symptoms.

Include catecholamine effects.

Back 8

HA
Palpitations
Sweating

Which occur in spells (paroxysms)

Hard to control HTN, HTN in paroxysms, orthostatic hypotn (catecholamine effects--vascularly constricted, volume depleted)

Catecholamines inhibit insulin-->hypoglycemia

Front 9

Who should we test for pheo?

Tests used for screening?
Include screening and confirmatory testing.

Back 9

Resistant HTN
Paroxysms suggestive of pheo
Genetic risk factors (MEN2, ret mutation)
Adrenal incidentaloma

Screen for catecholamines or metabolites
24 hour urine collection, plasma metanephrines!

Pheos continuously release metanephrines! very high sensitivity, but low specificity. needs confirmatory testing.

Confirm with 24 hour urine collection for catecholamines and MN.

Front 10

What substances interfere with pheo testing?

Back 10

Substances that rasise level of catechols or metabs or interfere with assay

Ex: Acetaminophen, antipsychotics, EtOH
Coffee (even decaf)
Labetalol, sotalol

Front 11

Clonidine Suppression Test:
Mechanism
Use

Back 11

Clonidine (anti-HTN) suppresses catechol release
Catechols should go down
If doesn't go down-->PHEO!

Front 12

Why should you NEVER run a glucagon stimulation test in someone with pheo?

Back 12

glucagon causes NE levels to rise 3x in pheo, which can be FATAL

Front 13

I123-MIBG Imaging

Back 13

Pheo will uptake radiolabeled MIBG and will show up on CT/MRI

Front 14

Pheo:
Pre-operative management - include dietary changes

Back 14

1) Alpha-blockade (phenoxybenzamine): may induce orthostatic hypotn, dizziness, syncope, congestion

If develop tachycardia, use beta-blockade (propanalol, atenelol)

ALWAYS alpha block before beta block

can also use Labetolol (combined alpha- and beta- blocker)

2) Salt loading (encourage high salt diet and liberal fluid intake while on phenoxybenzamine to reduce postop hypotn)

Front 15

Why should you administer alpha-blockade prior to beta-blockade?

Back 15

Alpha effect-->vasoconstriction
Beta effect-->vasodilation

If beta block first, unopposed alpha-adrenergic vasoconstriction can lead to hypertensive crisis

Front 16

Pheo:
Postoperative risks
Prevention?

Back 16

Risk of HYPOtension:
Catecholamine levels fall
alpha-blockade still active
reduced with PRE-OPERATIVE VOLUME LOADING
(give saline, high salt diet)

Risk of hypoglycemia:
Catechols suppress insulin secretion so after sx, insulin levels will rebound
(give sugar? make sure they eat? didn't say.)

Front 17

Neuroendocrine Tumors:
Arise in the _____

Back 17

throughout body
Arise in Resp Tract, pancreas, anywhere along GI tract (even appendix)

May be fnal or nonfnal

May arise sporadically or part of syndrome

Front 18

Multiple Endocrine Neoplasia Type 1:
Mutation
Manifestations

Back 18

MEN type 1
Mutation on MENIN (tumor suppressor gene)
Manifestations: Three P's
hyperPARA
Pituitary adenomas
Pancreatic Neuroendocrine Tumors: gastrinoma (secrete gastrin), insulinoma (secrete insulin), nonfnal

Front 19

Carcinoid syndrome:
Due to
Symptoms
Circulation Pattern
Testing

Back 19

Tumor secretion of 5-HT, vasoactive peptides (histamine, kallikreain, PGs)

Syx:
FLUSHING
Diarrhea
Wheezing
R-sided valvular heart dz

Liver inactivates serotonin so carcinoid syndrome implues tumor effluent reaching systemic circulation without passing through liver (liver mets may drain into hepatic vein)

Test: Urinary excretion of 5-HIAA (serotonin metabolite)

Front 20

VIPoma:
Symptoms

Back 20

Secretes vasoactive intestinal peptide

Syx: WDHA Syndrome
Watery diarrhea
hypokalemia
achlorhydria (low stomach acid production)

Test VIP level

aka pancreatic cholera; Verner-Morrison syndrome

Front 21

Glucagonoma:
Symptoms

Back 21

Syx:
Hyperglycemic
migratory necrolytic erythema

Front 22

Somatostatinoma:
Symptoms
Diagnostics

Back 22

Secretes SMS

Diabetes
Gallblader Dz (inhibits gallbladder contraction)
Diarrhea
(same side effects as octreotide when treating acromegaly)

Test: SMS level

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