Anda di halaman 1dari 48

Pheochromocytoma

Dr. Atallah Al-Ruhaily

Pheochromocytoma
1.
2.

Catecholamine Physiology/Pathophysiology
Clinical Presentation
1.
2.

3.

Diagnosis
1.
2.

4.

Epidemiology
Signs & Symptoms
Biochemical
Localization

Management
1.
2.
3.
4.

Preoperative
Operative
Postoperative
Pregnancy

Catecholamine Producing Tumors


Neural Crest
Sympathoadrenal Progenitor Cell
(Neuroblasts)

Chromaffin Cell

Neuroblastoma

Sympathetic Ganglion Cell

Intra-adrenal Extra-adrenal
Pheochromocytoma

Ganglioneuroma

Catecholamine Producing Tumors


Pheochromocytoma
Paraganglioma

(extra-adrenal pheo)

Originate in extra-adrenal sympathetic chain/chromaffin tissue

Ganglioneuroma

Behave like paraganglioma biochemically

Catecholamine Producing Tumors


Neuroblastoma

Common malignancy in children, adrenal or sympathetic chain


Catecholamine humoral effects usually minor
Rapid growth & widespread metastasis
Some differentiate and spontaneously regress
Rx complex (surgery, XRT, chemotherapy)

Cheodectoma

Carotid body, behave like paraganglioma biochemically

Glomus

jugulare tumor

Intracranial branch of CN IX and X


Behave like paragangliomoa biochemically

Catecholamines
Tyrosine

TH

L-Dopa

Dopamine

Metabolites
MAO, COMT

DBH

Homovanillic acid
(HVA)

NorepinephrineCOMT Normetanephrine
PNMT

Epinephrine

MAO
COMT

Tumor Secretion:
Large Pheo: more metabolites
(metabolized within tumor before release)
Small Pheo: more catecholamines
Sporadic Pheo: Norepi > Epi
Familial Pheo: Epi > Norepi
Paraganglioma: Norepi
Cheodectoma, glomus jugulare: Norepi
Gangioneuroma: Norepi
Malignant Pheo: Dopamine, HVA
Neuroblastoma: Dopamine, HVA

Metaneprine
MAO

Vanillymandelic Acid
(VMA)
PNMT:
Phenylethanolamine-NMethyl Transferase
COMT : Catechol-O-Methyl
Ttransferase
MAO: Mono-Amine Oxidase

Adrenergic Receptors
Alpha-Adrenergic

Receptors

1: vasoconstriction, intestinal relaxation, uterine


contraction, pupillary dilation
2: presynaptic NE (clonidine), platelet aggregation,
vasoconstriction, insulin secretion

Beta-Adrenergic

Receptors

1: HR/contractility, lipolysis, renin secretion

2: vasodilation, bronchodilation, glycogenolysis

3: lipolysis, brown fat thermogenesis

Pheochromocytoma
1.
2.

Catecholamine Physiology/Pathophysiology
Clinical Presentation
1.
2.

3.

Diagnosis
1.
2.

4.

Epidemiology
Signs & Symptoms
Biochemical
Localization

Management
1.
2.
3.
4.

Preoperative
Operative
Postoperative
Pregnancy

Pheochromocytoma
0.01-0.1%

of HTN population

Found in 0.5% of those screened

=F
3rd to 5th decades of life
Rare, investigate only if clinically suspicion:

Signs or Symptoms
Severe HTN, HTN crisis
Refractory HTN (> 3 drugs)
HTN present @ age < 20 or > 50 ?
Adrenal lesion found on imaging (ex. Incidentaloma)

Pheo: Signs & Symptoms


The

five Ps:

The

Pressure (HTN)
Pain (Headache)
Perspiration
Palpitation
Pallor

90%
80%
71%
64%
42%

Paroxysms

Classical Triad:

Pain (Headache), Perspiration, Palpitations


Lack of all 3 virtually excluded diagnosis of pheo in a series of
> 21,0000 patients

Pheo: Paroxysms, Spells


10-60

min duration
Frequency: daily to monthly
Spontaneous
Precipitated:

Diagnostic procedures, I.A. Contrast (I.V. is OK)


Drugs (opiods, unopposed -blockade, anesthesia induction,
histamine, ACTH, glucagon, metoclopramide)
Strenuous exercise, movement that increases intra-abdo
pressure (lifting, straining)
Micturition (bladder paraganlgioma)

Pheo: Hypotension!
Hypotension

(orthostatic/paroxysmal)
occurs in many patients
Mechanisms:
ECFv contraction
Loss of postural reflexes due to prolonged
catecholamine stimulation
Tumor release of adrenomedullin (vasodilatory
neuropeptide)

Pheo: Signs & Symptoms


N/V, abdo

pain, severe constipation (megacolon)


Chest-pains

Anxiety
Angina/MI with normal coronaries:
Catecholamine induced: myocardial oxygen consumption or
coronary vasospasm

CHF

HTN hypertrophic cardiomyopathy diastolic dysfn.


Catechols induce dilated cardiomyopathy systolic dysfn.

Cardiac

dysrhythmia & conduction defects

Pheo: Signs (metabolic)


Hypercalcemia
Associated MEN2 HPT
PTHrP secretion by pheo

Mild

glucose intolerance
Lipolysis
Weight-loss
Ketosis > VLDL synthesis (TG)

Pheo: Rule of 10
10%

extra-adrenal (closer to 15%)


10% occur in children
10% familial (closer to 20%)
10% bilateral or multiple (more if familial)
10% recur (more if extra-adrenal)
10% malignant
10% discovered incidentally

Familial Pheo

MEN 2a
50% Pheo (usually bilateral), MTC, HPT
MEN 2b
50% Pheo (usually bilatl), MTC, mucosal neuroma, marfanoid
habitus
Von Hippel-Landau
50% Pheo (usually bilat), retinoblastoma, cerebellar
hemangioma, nephroma, renal/pancreas cysts
NF1 (Von Recklinghausen's)
2% Pheo (50% if NF-1 and HTN)
Caf-au-lait spots, neurofibroma, optic glioma
Familial paraganglioma
Familial pheo & islet cell tumor
Other: Tuberous sclerosis, Sturge-Weber, ataxia-telangectgasia,
Carneys Triad (Pheo, Gastric Leiomyoma, Pulm chondroma)

Pheochromocytoma
1.
2.

Catecholamine Physiology/Pathophysiology
Clinical Presentation
1.
2.

3.

Diagnosis
1.
2.

4.

Epidemiology
Signs & Symptoms
Biochemical
Localization

Management
1.
2.
3.
4.

Preoperative
Operative
Postoperative
Pregnancy

24h Urine Collection


24h

urine collection:

Creatinine, catecholamines, metanephrines,


vanillymandelic acid (VMA), +/-dopamine
HPLC with electrochemical detection or mass spect

Positive

results (> 2-3 fold elevation):

24h Ucatechols > 2-fold elevation


ULN for total catechols 591-890 nmol/d

24h Utotal metanephrines > 1.2 ug/d (6.5 umol/d)


24h U
VMA > 3-fold elevation

ULN 35 umol/d for most assays

24h Urine Collection


Test

Characteristics:

24h Ucatechols

Sen 83% Spec 88%

24h Utotal metanephrines

Sen 76% Spec 94%

24h Ucatechols + Utotal metanephrines Sen 90% Spec 98%

24h UVMA

Sensitivity

Sen 63% Spec 94%

increased if 24h urine collection


begun at onset of a paroxysm

24h Urine: False Positive


Drugs:

TCAs, MAO-i, levodopa, methyldopa,


labetalol, propanolol, clonidine (withdrawal), ilicit
drugs (opiods, amphetamines, cocaine), ethanol,
sympathomimetics (cold remedies)
Hold these medications for 2 weeks!
Major physical stress (hypoglycemia, stroke,
raised ICP, etc.)
OSA

Plasma Catecholamines
Drawn

with patient fasting, supine, with an


indwelling catheter in place > 30 min
Plasma total catechols > 11.8 nM (2000 pg/mL)

SEN 85% SPEC 80%

False

positives: same as for 24h urine testing, also


with diuretics, smoking
CRF & ESRD:

Oliguric to Anuric 24h Urines inaccurate


Plasma epinephrine best test for pheo in ESRD
Plasma norepi and metanephrines falsely elevated in ESRD

Plasma Metanephrines
Not

postural dependent: can draw normally


Secreted continuously by pheo
SEN 99% SPEC 89%
False Positive: acetaminophen

Biochemical Tests: Summary


SEN

SPEC

Ucatechols

83%

88%

Utotal metanephrines

76%

94%

Ucatechols+metaneph

90%

98%

UVMA

63%

94%

Plasma catecholamines

85%

80%

Plasma metanephrines

99%

89%

Suppression/Stimulation Testing
Clonidine

suppression

May precipitate hypotensive shock!


Unlike normals, pheo patients wont suppress their
plasma norepi with clonidine

Glucagon

stimulation

May precipitate hypertensive crisis!


Pheo patients, but not normals, will have a > 3x
increase in plasma norepi with glucagon

Localization: Imaging
CT abdomen
Adrenal pheo SEN 93-100%
Extra-adrenal pheo SEN 90%

MRI

> SEN than CT for extra-adrenal pheo

Localization: Imaging
CT abdomen
Adrenal pheo SEN 93-100%
Extra-adrenal pheo SEN 90%

MRI

> SEN than CT for extra-adrenal pheo

MIBG

Scan

SEN 77-90% SPEC 95-100%

MIBG Scan
123I

or 131I labelled metaiodobenzylguanidine


MIBG catecholamine precurosr taken up by the
tumor
Inject MIBG, scan @ 24h, 48h, 72h
Lugols 1 gtt tid x 9d (from 2d prior until 7d after
MIBG injection to protect thyroid)
False negative scan:

Drugs: Labetalol, reserpine, TCAs, phenothiazines


Must hold these medications for 4-6 wk prior to scan

Localization: Nuclear medicine


MIBG
111Indium-pentreotide

Some pheo have somatostatin receptors

PET
F-fluorodeoxyglucose (FDG)
6-[18F]-fluorodopamine
18

Pheochromocytoma
1.
2.

Catecholamine Physiology/Pathophysiology
Clinical Presentation
1.
2.

3.

Diagnosis
1.
2.

4.

Epidemiology
Signs & Symptoms
Biochemical
Localization

Management
1.
2.
3.
4.

Preoperative
Operative
Postoperative
Pregnancy

Pheo Management
Prior

to 1951, reported mortality for excision of


pheochromoyctoma 24 - 50 %

HTN crisis, arrhythmia, MI, stroke


Hypotensive shock

Currently, mortality:

0 - 2.7 %

Preoperative preperation, -blockade?


New anesthetic techniques?
Anesthetic agents
Intraoperative monitoring: arterial line, EKG monitor, CVP
line, Swan-Ganz

Experienced

& Coordinated team:

Endocrinologist, Anesthesiologist and Surgeon

Preop W/up
CBC,

lytes, creatinine, INR/PTT

CXR
EKG
Echo

(r/o dilated CMY 2 catechols)

Preop Preperation Regimens


Combined

+ blockade

Phenoxybenzamine
Selective 1-blocker (ex. Prazosin)
Propanolol

Metyrosine
Calcium

Channel Blocker (CCB)

Nicardipine

Preop: + blockade
Start

at least 10-14d preop


Allow sufficient time for ECFv re-expansion

Phenoxybenzamine

Special pharmacy access only (no DIN)


Drug of choice
Covalently binds -receptors (1 > 2)
Start 10 mg po bid increase q2d by 10-20 mg/d
Increase until BP cntrl and no more paroxysms
Maintenance 40-80 mg/d (some need > 200 mg/d)
Salt load: NaCl 600 mg od-tid as tolerated

Preop: + blockade
Phenoxybenzamine

Side-effect: orthostasis with dosage required to normalized


seated BP, reflex tachycardia
Drawback: periop hypotension/shock unlikely to respond to
pressor agent.

Selective

(contd)

1-blockers

Prazosin, Terazosin, Doxazosin


Some experience with Prazosin for Pheo preop prep
Not routinely used as incomplete -blockade
Less orthostasis & reflex tachycardia then phenoxybenzamine
Used more for long-term Rx (inoperable or malignant pheo)

Preop: + blockade
-blockade
Used to control reflex tachycardia and prophylaxis
against arrhythmia during surgery
Start only after effective -blockade (may ppt HTN)
If suspect CHF/dilated CMY start low dose
Propanolol most studied in pheo prep

Start 10 mg po bid increase to cntrl HR

Preop: + blockade
If

BP still not cntrl despite + blockade


Add Prazosin to Phenoxybenzamine
Add CCB, ACE-I
Avoid diuretics as already ECFv contracted
Metyrosine

Preop: + blockade
Meds

given on AM of surgery
Periop HTN:

IV phentolamine
Short acting non-selective -blocker
Test dose 1 mg, then 2-5 mg IV q1-2h PRN or as continuous
infusion (100 mg in 500cc D5W, titrate to BP)

IV Nitroprusside (NTP)

Periop

arrhythmia: IV esmolol
Periop Hypothension: IV crystalloid +/- colloid

Pheo: Rx of HTN Crisis


IV phentolamine
IV NTP
IV esmolol
IV labetalol

combined + blocker

Preop: Metyrosine
Tyrosine

TH

L-Dopa

Dopamine

DBH
Synthetic inhibitor of Tyrosine
Hydroxylase (TH)
Norepinephrine
Special pharm access, no DIN
PNMT
Start 250 mg qid max 1 gm qid
Severe S/Es: sedation, extrapyramidal, diarrhea,
Epinephrine
nausea/vomit, anxiety, renal/chole stones, galactorrhea
Alone may insufficiently cntrl BP and reported HTN crises
during pheo operation
Restrict use to inoperable/malignant pheo or as adjunct to
+ blockade or other preop prep

Preop: CCB

CCB

Nicardipine: most commonly used agent


Nicardipine (France Study)

Block norepi mediated Ca transport into vascular smooth


muscle

Started po 24h to few weeks preop to cntrl BP and allow ECFv


restoration
After intubation IV Nicardipine gtt (start 2.5 ug/kg/min)
IV Nicardipine adjusted to SBP
Stopped prior to ligation of tumor venous drainage
Tachycardia Rx with concurrent IV esmolol

Advantage: periop hypotension may still respond to pressor agents


as opposed to those patients who are completely -blocked

O.R.
Admit

night before for overnight IV saline


Arterial line, EKG monitor, CVP line
Known CHF: consider Swan-Ganz
Regardless of preop medications:
Have ready: IV phentolamine, IV NTP, IV esmolol
Rx hypotension with crystalloid +/- colloid 1 st
Aim for CVP 12 or Wedge 15
Inotropes may not work!

O.R.
Anesthetic

choice:

Enflurane or isoflurane: dont sensitized


myocardium to catecholamines
Halothane: may sensitize heart arrhythmia

Laprascopic

adrenalectomy if tumor < 8cm

Postop
Most

cases can stop all BP meds postop

Postop hypotension: IV crystalloid


HTN free:
5 years 74% 10 years 45%

24h

urine collection 2 wk postop


Surveillance:
24h urine collections q1y for at least 10y
Lifelong f/up

Pheo: Unresectable, Malignant


-blockade

Selective 1-blockers (Prazosin, Terazosin, Doxazosin) 1 st line


as less side-effects
Phenoxybenzamine: more complete -blockade

-blocker
CCB, ACE-I,

etc.
Nuclear Medicine Rx:

Hi dose 131I-MIBG or 111indium-octreotide depending on


MIBG scan or octreoscan pick-up
Sensitize tumor with Carboplatin + 5-FU

Pheo & Pregnancy


Diagnosis

with 24h urine collections and MRI


No stimulation tests, no MIBG if pregnant
1st & 2nd trimester (< 24 weeks):

3rd

Phenoxybenzamine + blocker prep


Resect tumor ASAP laprascopically

trimester:

Phenoxybenzamine + blocker prep


When fetus large enough: cesarian section followed by tumor
resection

Anda mungkin juga menyukai