Pheochromocytoma Flashcards
Epinephrine
Synthesized and stored where?
what % of catecholamine released by the adrenal medula?
adrenal medulla
80%
Norepinephrine
Synthesized & stored where?
adrenal medulla and peripheral sympathetic nerves
Dopamine
Precursor for what?
stored where?
used as a neurotransmitter where?
Norepinephrine
adrenal medulla & peripheral sympathetic nerves
CNS
The biologic 1/2 life of catecholamines is what?
10-100 seconds
Concentrations vary d/t loose association with what?
albumin
Eliminated from circulation via what routes?
What is the most common?
reuptake by sympathetic nerve endings (most common)
Metabolized
Conjugated
renally excreted
Catecholamines affect what?
Actions are mediated by what?
HR
BP
contractility
conduction velocity
adrenergic receptors
Alpha 1 receptors mediate what?
vascular & smooth muscle contraction
stimulation = vasoconstriction and increased BP
Alpha 2 receptors mediate what?
the inhibition of NE release
Beta 1 receptor stimulation leads to what effects?
+ Inotropy
+ Chronotropy
Increased renin secretion from kidneys
Lipolysis in fat cells
bronchodilation
vasodilation in skeletal muscle
glycogenolysis
Increased NE release from sympathetic nerve endings
Beta 2 receptor stimulation leads to what effects?
Smooth muscle relaxation
Bronchodilation
Hepatic glycogenolysis
pancreatic release of glucagon
Beta 3 receptor stimulation leads to what effects?
regulates lipolysis & energy expenditure
Dopamine 1 (DA1) receptor are located where?
Stimulation leads to what?
Cerebral, coronary, mesenteric, & renal beds
vasodilation
Dopamine 2 (DA2) receptors are located where?
Stimulation leads to what effects?
presynaptic & localized to sympathetic nerve endings, sympathetic ganglia, & the brain
inhibition of NE
Types of Catecholamine secreting tumors from chromaffin cells
Pheochromocytoma (from adrenal medulla)
Extra-adrenal catecholamine-secreting paragangliomas (outside adrenal medulla)
Hereditary types of Pheochromocytomas
autosomal dominant
Constellation includes adrenal pheo, thyroid Ca, & hyperparathyroiidism
Multiple Endocrine Neoplasia (MEN) type 2a
Hereditary types of Pheochromocytomas
autosomal dominant
Pheo, thyroid Ca, mucosal neuromas, thick corneal nerves, intestinal ganglioneuromatosis, marfan features
Multiple Endocrine Neoplasia (MEN) type 2b
Hereditary types of Pheochromocytomas
Autoasomal dominant
neurofibromas, cafe au lait spots, freckling of axilla, inguinal areas, 2% develop adrenal pheo’s
Neurofibromatosis
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?
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
“Spell” related clinical manifestations
HTN (chronic or episodic)
Anxiety
Diaphoresis
Epigastric/chest pain
Headache
N/V
Pallor
Palpitations
Tremor
Chronic related clinical manifestations
Anxiet
Cold hands & feet
Constipation
Diaphoresis
Epigastric/chest pain
Fatigue
Fever
Retinopathy
Headache
Hyperglycemia
HTN
Pallor
Palpitations
Tremor
Wt. loss
Orthostatic hypotension
Other disorders that could mimic Pheo include?
Idiopathic hypotension
Panic d/o
Withdrawal from adrenergic inhibitor (beta blocker)
Angina
Hyperthyroidism
Insulinoma
Menopause
PSVT
Pulmonary edema
Renovascular HTN
SAH
Pheo should be suspected if the patient as 1 or more of the following
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
Physical Exam findings may include?
sustained/paroxysmal HTN
Generalized sweating
tachycardia
postural hypotension
Tremor
HTN retinopathy
Labs to get for suspicion of pheo
Plasma metanephrine OR
24 hr urine for metanephrines
24 hr urine for metanephrines positive results are
2.2mcg of total metanephrine/gm creatinine
135mcg total catecholamines/gm creatinine
False (+) results are common, what can you do to confirm if you suspect a false positive?
Repeat sampling in supine position
Clonidine suppression test with measurement of plasma normetanephrine
Chromogranin & urinary fractionated metanephrines measurements
Meds that may cause falsely elevated results include?
TCADs
levodopa
acetaminophen
cocaine
MAOIs
Amphetamines
buspar
labetalol
What is the indication for a Clonidine Suppression test?
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.
What conditions must be met prior to a clonidine suppression test?
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
Clonidine Suppression Test procedure
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
Interpretation of a Clonidine Suppression test
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
When to get Imaging to confirm diagnosis?
obtain after labs
1st line imaging is?
CT abdomen/pelvis
MRI should be used for what?
metastatic PPGLs
Skull base & neck paragangliomas
Surgical clips in place
allergy to CT contrast
when XRT should be limited
PET CT in patients with what?
mets
Genetic Testing
Decision should be made how?
How many different genes are linked to PPGL?
Use what to determine need for genetic testing?
Shared decision making
14
clinical feature-driven diagnostic algorithm to determine genetic testing
Consider what as prompts for the need of genetic testing?
Younger age of presentation
family hx
multifocal PPGLs
BL adrenal tumors
Management
Personalized approach includes?
Treatment of choice?
testing, imaging, surgery, f/u
Surgical resection
Pre-op medications management
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
Beta-blocker therapy to use for pre-op management
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)
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?
BP, HR, glucose monitoring
2-4 wks
annually d/t reports of high rates of recurrence or mets after resection
Expected Outcomes
Symptoms/HTN usually do what?
Requires what?
Survival rate if malignant?
resolve or improve w/ tx
lifelong monitoring
<50%
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?
bad prognosis
48%; 55%
dibenzyline
1st or 2nd trimester
3rd trimester resection followed by C section
abortion
