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
Chromaffin Cell
Neuroblastoma
Intra-adrenal Extra-adrenal
Pheochromocytoma
Ganglioneuroma
(extra-adrenal pheo)
Ganglioneuroma
Cheodectoma
Glomus
jugulare tumor
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
Beta-Adrenergic
Receptors
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
=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)
five Ps:
The
Pressure (HTN)
Pain (Headache)
Perspiration
Palpitation
Pallor
90%
80%
71%
64%
42%
Paroxysms
Classical Triad:
min duration
Frequency: daily to monthly
Spontaneous
Precipitated:
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)
Anxiety
Angina/MI with normal coronaries:
Catecholamine induced: myocardial oxygen consumption or
coronary vasospasm
CHF
Cardiac
Mild
glucose intolerance
Lipolysis
Weight-loss
Ketosis > VLDL synthesis (TG)
Pheo: Rule of 10
10%
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
urine collection:
Positive
Characteristics:
24h Ucatechols
24h UVMA
Sensitivity
Plasma Catecholamines
Drawn
False
Plasma Metanephrines
Not
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
Glucagon
stimulation
Localization: Imaging
CT abdomen
Adrenal pheo SEN 93-100%
Extra-adrenal pheo SEN 90%
MRI
Localization: Imaging
CT abdomen
Adrenal pheo SEN 93-100%
Extra-adrenal pheo SEN 90%
MRI
MIBG
Scan
MIBG Scan
123I
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
Currently, mortality:
0 - 2.7 %
Experienced
Preop W/up
CBC,
CXR
EKG
Echo
+ blockade
Phenoxybenzamine
Selective 1-blocker (ex. Prazosin)
Propanolol
Metyrosine
Calcium
Nicardipine
Preop: + blockade
Start
Phenoxybenzamine
Preop: + blockade
Phenoxybenzamine
Selective
(contd)
1-blockers
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
Preop: + blockade
If
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
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
O.R.
Admit
O.R.
Anesthetic
choice:
Laprascopic
Postop
Most
24h
-blocker
CCB, ACE-I,
etc.
Nuclear Medicine Rx:
3rd
trimester: