Internal Medicine
Residents Rounds
Juan Rivera, MD
Pheochromocytomas
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Rare tumors
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Pheos should be suspected, confirmed, localized,
and resected because:
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Less than 0.2% of HTN
2 / million / year
More frequent in autopsy series (250 – 1300 / million)
Aldosteronism is much more common
HTN is curable
Paroxysms can be lethal
10% are malignant
Occur in both sexes and at any age, but more in
the 4th – 5th decades of life
Who should be screened?
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Episodic or very labile HTN
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Shock or severe pressor responses with:
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induction of anesthesia, intubation, surgery, parturition,
invasive procedures and antihypertensive drugs
Adverse CV response to certain drugs:
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Anesthetics, glucagon, TRH, ACTH, naloxone, beta
blockers, TCA, histamine.
Who should be screened?
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Spells of: headache, tachycardia, diaphoresis, anxiety
attacks (c/s HTN)
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Occurring during exercise, twisting of the torso, straining
(Valsalva), coitus, or micturition.
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Family history of pheochromocytoma or MTC
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Hypertensive patients with:
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Unexplained weight loss, diaphoresis, constipation,
orthostatic hypotension, seizures, cold hands and feet
Incidental adrenal or abdominal mass
Spells Phenotypes
Pheo
Carcinoid
 Perspiration
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 Palpitation
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 Pain
 Pallor
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 Pressure
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Flushing
Abdo pain: Intermittent
intestinal obstruction or
ischemia
Diarrhea
Bronchospam
Hypotension or rarely
Mastocytosis
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 Plethora of manif:
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tremor, anxiety, N&V,
HTN
weakness, wt loss, dyspnea,
 Nasal congestion &
warmth, visual disturb,
periocular edema
dizziness, orthostatism,
constipatn, paresthesias,
 Symptoms of pulmonic
BG, painless hematuria.
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 Rarely:
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flushing
typical feature)
(not a
stenosis or tricuspid
insufficiency
 Triggers: excitement,
 Triggers: postural change, alcohol ingestion,
catecholamines, chocolates.
anxiety, exercise.
 Duration: 2 – 5 min
 Duration: 10-60 min
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Flushing and facial warmth
Pallor (if abrupt  BP)
Palpitations
Lightheadedness or
syncope
Dyspnea and c/p
N,V,D
Pruritus
Fatigue and profound
lethargy after the spell
Triggers: heat, exertion,
emotional upset, ethanol,
narcotics, anticholinergics,
radiocontrast agents.
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Typical duration: 15-30mi
Frequency: daily to 3 times
annually
Other causes of spells
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Endocrine:
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Anxiety & panic attacks
Somatization disorders
Miscellaneous:
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Labile essential HTN
Renovascular disease
Angina
Psychiatric:
Polycytemia Vera
Pharmacologic
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Thyrotoxicosis
Menopausal syndrome
Medullary thyroid ca
Hypoglycemia
Cardiovascular:
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Antidepressants (SSRI)
Sildenafil
Niacin
CCB
Opiates
Tamoxifen, bromocriptin
Cocaine, LSD
Vancomycin
EtOH + metronidazol / Ketoconazol /
chlorpropamide /cephalosporines
Neurologic
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POTS
Autonomic neuropathy
Migraine headache
Seizure disorder
Non-classical Symptoms
Abdominal pain
 Vomiting
 Dyspnea
 Heart failure
 Hypotension
 Sudden death
 Fever (IL-6)
 Cushings sd
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Other findings
Leucocytosis
 Hyperglycemia (CA)
 Hypercalcemia (PTHrp)
 Hypokalemia (CA)
 Erythrocytosis (Erythropoietin)
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What is the best screening test?
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Options:
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Resting plasma catecholamines (CA)
Plasma Metanephrines (MN)
24h urine CA + MN
We use 24h-urine CA + MN
Screening Tests
Plasma CA
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Urine CA + MN
Plasma MN
From indwelling
 Acidified container  Very sensitive (97cath, supine x 30min
 If omitted, keep cold,
99%)
process immediate
Total CA (N<4.2 nmol/L)
 Specificity is low
 > 12  dx
 Urine MN:
(82%)
 6-12 highly sugg
 Least susceptible to
 except in hereditary
False positive are
interference
syndromes (96%)
(labetalol, buspirone)
frequent
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> 6,500 nmol/d 
highly suggest
 ~ 90% specific
Medications, food,
stress
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VMA: unacceptably
high false negative
rate (41%)
A 72 y.o. male
Admitted because of colon ca
 Abdomen CT shows a 12cm mass on the
right adrenal
 Endo sees the patient and concludes that
this is most likely metastasis. Cosyntropin
test normal.
 24h-urine CA + MN: normal except for DA
= 32,000 (N < 2,630)
 What’s going on?
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A 72 y.o. male with Colon ca and an
adrenal mass
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Patient on treatment with Sinemet for
Parkinson
Interference
DRUGS
FOODS AND OTHERS
• Acetaminofen
•Bananas (NE)
•Benzodiazepines
•Caffeine
•Buspirone
•Nicotine
•Diuretics
•Exercise
•Levodopa
•Sympathomimetics
•TCA
•Vasodilators
•Tetracycline and quinidine
•Ethanol
Westphal: Am J Med Sci, Volume 329(1).January 2005.18-21
An 82 y.o. male
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While on vacation in Florida consults because on
dyspnea
A chest CT notes a 3 cm mass in the right
adrenal
Patient otherwise healthy, “never sick”,
completely asymptomatic, BP 100/60, physical
exam unremarkable
24h-urine CA + MN:
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E  25 (-136); NE  3678 (-591)
MN  645 (281-1841); NMN 21740 (502-2531)
Why are some PHEO patients normotensive
despite high circulating cathecolamines?
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Chronically hypovolemics
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Increase production of vasodilator agents
(DOPA acting in the CNS; dopamine acting on
mesenteric and renal vessels; prostaglandins)
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Adrenergic desensitization: down-regulation of
alpha-1 receptors
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Polymorphism in beta-2 receptors that allows
continued b2-mediated vasodilation
Can radiology help?
MRI
CT
Radiol.
Feature
Adenomas
Pheochrom
Cancer
Size
< 4 cm
Variable. Mean 4cm
90% > 4 cm
Attenuation
s contrast
Low < 10 HU
Variable high
Calcifications +
High >10 HU
Calcifications +
Attenuation
w contrast
Low enhancemt <40 High enhancemt
Inhomogeneous
Early washout
- 50% at 5min
-70% at 15min
Slow washout
-8% at 5 min;
-20% at 15 min
areas of necrosis
Signal
Intensity
(c/c liver)
Isointense on
T1&T2
Hypointense on T1 Hyper or Iso on T2
Hyperintens on T2 Mets can be isointense
Enhancement
Mild
Rapid and marked
Variable
Wash-out
Rapid
Slow
Slow
Bright on “in-phase”
images
Low signal on
“out-of-phase” ima
Chemical Shift
Imaging (CSI)
b/o
Slow washout
> 40 HU at 30 min
Transverse CT scans obtained in 49-year-old woman with adrenal
pheochromocytoma. (a) Nonenhanced scan obtained at level of middle
portion of left adrenal gland shows well-defined mass (arrows) with
isoattenuation relative to liver parenchyma. (b, c) Contrast-enhanced scans
obtained at same level as in a. The tumor (arrows) has heterogeneous
enhancement on (b) the 1-minute scan and homogeneous enhancement on
(c) the 10-minute scan. Tumor attenuation is 56 HU in a, 107 HU in b, and
94 HU in c. Thus, the absolute percentage of enhancement loss in this tumor
is 25%, and the relative percentage of enhancement loss is 12%.
Pre-op
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A 39-year-old woman comes to your office
complaining of episodic anxiety, headache, and
palpitations. She states that without dieting she
has lost 15 pounds over the past 6 months.
Physical examination is normal except for a blood
pressure of 200/100 mm Hg and a resting pulse
rate of 110 bpm. Chart review shows that prior
blood pressures have always been normal,
including one 6 months ago. The diagnosis of
pheochromocytoma is confirmed, and a 3 cm
mass is visualized on the right adrenal by MRI.
Question:
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How do you prepare her for OR?
General Measures
High PO fluid intake at home
 Generous hydration 24-48h pre-op once
admitted
 Teach self-monitoring of BP (BID & PRN)
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Medical Therapy
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CCB:
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Nicardipine, Amlodipine, Nifedipine or verapamil
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Advantages: better tolerated, less perioperative fluids, fast
and effective during paroxysms, in vitro nifedipine reduces
proliferation of pheo cells
Alpha-adrenergic blockade
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Phenoxybenzamine: start 10 mg/day, increase q3d to 3060 mg/d
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Problems: takes longer to control BP, worse post-op
hypotension, SE (dry mouth, h/a, diplopia, nasal congestion),
not during pregnancy (accumulates in the fetus).
Selective alpha-1: Doxazosin, prazosin
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Advantages: short acting (prazosin< doxazosin), less reflex
tachy, less post-op hypotension
Medical Therapy
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ACE inhibitors and ARBs
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Beta blockers
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CA  ^ renin  etc
Pheos have ACE binding sites
Should not be use as sole agent
Only after alpha-blockade or CC blockade
Metoprolol, labetalol, propranolol
Metyrosine
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Inhibits tyrosine hydroxylase
Used as adjuvant when uncontrolled HTN prior to surgery
Reported to reduce intraop HTN and arrhythmias
Postop hypotension may be more severe for several days
SE:sedation, psychiatric, nightmares, diarrhea, galactorrhea,
extrapyramidal sx, crystalluria and urolithiasis
That’s it
Thanks
Sorry…
THAT’S NOT
THE CORRECT
ANSWER
YOUR ANSWER
IS CORRECT!!!
Pathophysiologic & Clinical Manifestations of CA Excess1
Target Tissue
Physiologic Effect
Pathophysiologic Manifestations
Arteriolar constriction
Tachycardia
Tachyarrhythmia
Increased myocardial O2
consumption
Myocarditis
Cardiomyopathy
Hypertension
Venoconstriction
Decreased plasma volume
Gut
Intestinal relaxation
Impaired intestinal motility
Pancreas (B cells)
Suppression of insulin
release
Increased glucose output
Carbohydrate intolerance
Lipolysis
Stimulation
Contraction
Increased basal metabolic
rate
Increased free fatty acids
Sweating
Elevated urethral pressures
Increased heat production
Heart
Increased heart rate
Increased contractility
Blood vessels
Liver
Adipose
Skin (apocrine glands)
Bladder neck
Most tissues
1Modified,
Carbohydrate intolerance
Clinical Manifestations
Palpitations
Angina pectoris
Angina pectoris
Congestive heart failure
Headache
Congestive heart failure
Angina pectoris
Dizziness
Orthostatic hypotension
Circulatory collapse
Ileus
Obstipation
Hyperglycemia
Glucosuria
Hyperglycemia
Glucosuria
Weight loss
Diaphoresis
Urinary retention
Heat intolerance
Sweating
Weight loss
with permission, from Werbel SS, Ober KP: Pheochromocytoma: Update on diagnosis, localization,
and management. Med Clin North Am 1995;79:131.