Pheochromocytoma

Question 1

Epinephrine
Synthesized and stored where?
what % of catecholamine released by the adrenal medula?

Answer 1

adrenal medulla
80%

Question 2

Norepinephrine
Synthesized & stored where?

Answer 2

adrenal medulla and peripheral sympathetic nerves

Question 3

Dopamine
Precursor for what?
stored where?
used as a neurotransmitter where?

Answer 3

Norepinephrine
adrenal medulla & peripheral sympathetic nerves
CNS

Question 4

The biologic 1/2 life of catecholamines is what?

Answer 4

10-100 seconds

Question 5

Concentrations vary d/t loose association with what?

Answer 5

albumin

Question 6

Eliminated from circulation via what routes?
What is the most common?

Answer 6

reuptake by sympathetic nerve endings (most common)
Metabolized
Conjugated
renally excreted

Question 7

Catecholamines affect what?

Actions are mediated by what?

Answer 7

HR
BP
contractility
conduction velocity

adrenergic receptors

Question 8

Alpha 1 receptors mediate what?

Answer 8

vascular & smooth muscle contraction
stimulation = vasoconstriction and increased BP

Question 9

Alpha 2 receptors mediate what?

Answer 9

the inhibition of NE release

Question 10

Beta 1 receptor stimulation leads to what effects?

Answer 10

+ Inotropy
+ Chronotropy
Increased renin secretion from kidneys
Lipolysis in fat cells
bronchodilation
vasodilation in skeletal muscle
glycogenolysis
Increased NE release from sympathetic nerve endings

Question 11

Beta 2 receptor stimulation leads to what effects?

Answer 11

Smooth muscle relaxation
Bronchodilation
Hepatic glycogenolysis
pancreatic release of glucagon

Question 12

Beta 3 receptor stimulation leads to what effects?

Answer 12

regulates lipolysis & energy expenditure

Question 13

Dopamine 1 (DA1) receptor are located where?
Stimulation leads to what?

Answer 13

Cerebral, coronary, mesenteric, & renal beds
vasodilation

Question 14

Dopamine 2 (DA2) receptors are located where?
Stimulation leads to what effects?

Answer 14

presynaptic & localized to sympathetic nerve endings, sympathetic ganglia, & the brain
inhibition of NE

Question 15

Types of Catecholamine secreting tumors from chromaffin cells

Answer 15

Pheochromocytoma (from adrenal medulla)
Extra-adrenal catecholamine-secreting paragangliomas (outside adrenal medulla)

Question 16

Hereditary types of Pheochromocytomas
autosomal dominant
Constellation includes adrenal pheo, thyroid Ca, & hyperparathyroiidism

Answer 16

Multiple Endocrine Neoplasia (MEN) type 2a

Question 17

Hereditary types of Pheochromocytomas
autosomal dominant
Pheo, thyroid Ca, mucosal neuromas, thick corneal nerves, intestinal ganglioneuromatosis, marfan features

Answer 17

Multiple Endocrine Neoplasia (MEN) type 2b

Question 18

Hereditary types of Pheochromocytomas
Autoasomal dominant
neurofibromas, cafe au lait spots, freckling of axilla, inguinal areas, 2% develop adrenal pheo’s

Answer 18

Neurofibromatosis

Question 19

Clinical Manifestations
Result from?
May be spurred by?
“Spells” may occur at what frequency?
May be associated with?
May have what that can go unrecognized?

Answer 19

excess concentrations of catecholamines
anxiety, meds (reglan, anesthesia), postural change, exercise, increased abd. pressure
multiple times/day or q month & typically last 15-20 min
with co-secreted hormones (ACTH-Cushings, parathyroid hormone-hypercalcemia, vasopressin-SIADH, growth hormone-acromegaly)
cardiomyopathy & CHF

Question 20

“Spell” related clinical manifestations

Answer 20

HTN (chronic or episodic)
Anxiety
Diaphoresis
Epigastric/chest pain
Headache
N/V
Pallor
Palpitations
Tremor

Question 21

Chronic related clinical manifestations

Answer 21

Anxiet
Cold hands & feet
Constipation
Diaphoresis
Epigastric/chest pain
Fatigue
Fever
Retinopathy
Headache
Hyperglycemia
HTN
Pallor
Palpitations
Tremor
Wt. loss
Orthostatic hypotension

Question 22

Other disorders that could mimic Pheo include?

Answer 22

Idiopathic hypotension
Panic d/o
Withdrawal from adrenergic inhibitor (beta blocker)
Angina
Hyperthyroidism
Insulinoma
Menopause
PSVT
Pulmonary edema
Renovascular HTN
SAH

Question 23

Pheo should be suspected if the patient as 1 or more of the following

Answer 23

Severe, sudden, unexplained HTN
Hyperadrenergic spells
Resistant HTN
Family hx
Resected pheo with recurrent HTN or spells
Incidental adrenal mass
Early onset HTN (<20yrs)
Idiopathic Cardiomyopathy

Question 24

Physical Exam findings may include?

Answer 24

sustained/paroxysmal HTN
Generalized sweating
tachycardia
postural hypotension
Tremor
HTN retinopathy

Question 25

Labs to get for suspicion of pheo

Answer 25

Plasma metanephrine OR 24 hr urine for metanephrines

Question 26

24 hr urine for metanephrines positive results are

Answer 26

2.2mcg of total metanephrine/gm creatinine 135mcg total catecholamines/gm creatinine

Question 27

False (+) results are common, what can you do to confirm if you suspect a false positive?

Answer 27

Repeat sampling in supine position Clonidine suppression test with measurement of plasma normetanephrine Chromogranin & urinary fractionated metanephrines measurements

Question 28

Meds that may cause falsely elevated results include?

Answer 28

TCADs levodopa acetaminophen cocaine MAOIs Amphetamines buspar labetalol

Question 29

What is the indication for a Clonidine Suppression test?

Answer 29

To discriminate patients with mildly elevated test results for plasma normetanephrine due to increased sympathetic activity from patients with elevated results due to a PPGL.

Question 30

What conditions must be met prior to a clonidine suppression test?

Answer 30

Withdraw sympatholytic drugs before testing (e.g. beta blocker) 48 hrs prior to testing The test is carried out with patient in the supine position The test is cancelled if baseline blood pressure is < 110/60 mmHg or in volume-depleted patients

Question 31

Clonidine Suppression Test procedure

Answer 31

A PIV is placed in the AC After 20 min of supine rest, a first blood sample is drawn Clonidine is administered 300 nanogram/70kg body weight BP and HR are measured at regular intervals before and during the test Three hours after drug administration a second blood sample is drawn The tubes with blood samples must immediately be placed on ice Blood samples are then analyzed for normetanephrines

Question 32

Interpretation of a Clonidine Suppression test

Answer 32

An abnormal test resulting in a PPGL includes an elevation of plasma normetanephrines at 3h after clonidine admin and a less than 40% decrease in levels compared with baseline

Question 33

When to get Imaging to confirm diagnosis?

Answer 33

obtain after labs

Question 34

1st line imaging is?

Answer 34

CT abdomen/pelvis

Question 35

MRI should be used for what?

Answer 35

metastatic PPGLs Skull base & neck paragangliomas Surgical clips in place allergy to CT contrast when XRT should be limited

Question 36

PET CT in patients with what?

Answer 36

mets

Question 37

Genetic Testing Decision should be made how? How many different genes are linked to PPGL? Use what to determine need for genetic testing?

Answer 37

Shared decision making 14 clinical feature-driven diagnostic algorithm to determine genetic testing

Question 38

Consider what as prompts for the need of genetic testing?

Answer 38

Younger age of presentation family hx multifocal PPGLs BL adrenal tumors

Question 39

Management Personalized approach includes? Treatment of choice?

Answer 39

testing, imaging, surgery, f/u Surgical resection

Question 40

Pre-op medications management

Answer 40

Utilize Alpha & beta blockers for pre-op BP control Phenoxybenzamine (dibenzyline) 10 mg BID up to 1mg/kg/d (start 7-14 days prior to surgery) start before beta blocker therapy to avoid unopposed alpha stimulation & HTN crisis

Question 41

Beta-blocker therapy to use for pre-op management

Answer 41

Propranolol 20 mg tid up to 40mg TID after @ least 3-4d of alpha blocker nonselective beta blocers (blocks 1&2) OR Atenolol 25 mg qd up to 50mg qd cardioselective (beta 1)

Question 42

Follow up monitoring in immediate post-op period includes? Biochemical testing to document successful tumor removal when? Check plasma or urine metanephrines how often after surgery? why?

Answer 42

BP, HR, glucose monitoring 2-4 wks annually d/t reports of high rates of recurrence or mets after resection

Question 43

Expected Outcomes Symptoms/HTN usually do what? Requires what? Survival rate if malignant?

Answer 43

resolve or improve w/ tx lifelong monitoring <50%

Question 44

Pregnancy Pheo + pregnancy = ? Mortality rate for mom? baby? what should be given as soon as dx is made? Tumor resection is ideally done when? If unable to complete resection during optimal time what must happen? Spontaneous what is likely?

Answer 44

bad prognosis 48%; 55% dibenzyline 1st or 2nd trimester 3rd trimester resection followed by C section abortion