Internal Medicine Residents Rounds

Juan Rivera, MD

Pheochromocytomas Rare tumors

Less than 0.2% of HTN 2 / million / year More frequent in autopsy series (250 – 1300 / million) Aldosteronism is much more common

Pheos should be suspected, confirmed, localized, and resected because: 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? Episodic or very labile HTN

Shock or severe pressor responses with: induction of anesthesia, intubation, surgery, parturition,

invasive procedures and antihypertensive drugs

Adverse CV response to certain drugs: Anesthetics, glucagon, TRH, ACTH, naloxone, beta

blockers, TCA, histamine.

Who should be screened? Spells of: headache, tachycardia, diaphoresis, anxiety

attacks (c/s HTN)

Occurring during exercise, twisting of the torso, straining

(Valsalva), coitus, or micturition.

Family history of pheochromocytoma or MTC

Hypertensive patients with: Unexplained weight loss, diaphoresis, constipation,

orthostatic hypotension, seizures, cold hands and feet

Incidental adrenal or abdominal mass

Spells Phenotypes

PerspirationPalpitationPainPallorPressurePlethora of manif:

tremor, anxiety, N&V, weakness, wt loss, dyspnea, warmth, visual disturb, dizziness, orthostatism, constipatn, paresthesias, BG, painless hematuria.

Rarely: flushing (not a typical feature)

Triggers: postural change,

anxiety, exercise.

Duration: 10-60 min

Flushing Abdo pain: Intermittent

intestinal obstruction or ischemia

Diarrhea Bronchospam Hypotension or rarely

HTN Nasal congestion &

periocular edema Symptoms of pulmonic

stenosis or tricuspid insufficiency

Triggers: excitement, alcohol ingestion, catecholamines, chocolates.

Duration: 2 – 5 min

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.

Typical duration: 15-30mi

Frequency: daily to 3 times annually

Pheo Carcinoid Mastocytosis

Other causes of spells

Endocrine: Thyrotoxicosis Menopausal syndrome Medullary thyroid ca Hypoglycemia

Cardiovascular: Labile essential HTN Renovascular disease Angina

Psychiatric: Anxiety & panic attacks Somatization disorders

Miscellaneous: Polycytemia Vera

Pharmacologic Antidepressants (SSRI) Sildenafil Niacin CCB Opiates Tamoxifen, bromocriptin Cocaine, LSD Vancomycin EtOH + metronidazol / Ketoconazol /

chlorpropamide /cephalosporines

Neurologic POTS Autonomic neuropathy Migraine headache Seizure disorder

Non-classical Symptoms Abdominal pain Vomiting Dyspnea Heart failure Hypotension Sudden death Fever (IL-6) Cushings sd

Other findings Leucocytosis Hyperglycemia (CA) Hypercalcemia (PTHrp) Hypokalemia (CA) Erythrocytosis (Erythropoietin)

What is the best screening test?

Options: Resting plasma catecholamines (CA) Plasma Metanephrines (MN) 24h urine CA + MN

We use 24h-urine CA + MN

Screening Tests

From indwelling cath, supine x 30min

Total CA (N<4.2 nmol/L)

> 12 dx 6-12 highly sugg

False positive are frequent

Medications, food, stress

Acidified container If omitted, keep cold,

process immediate

Urine MN: Least susceptible to

interference (labetalol, buspirone)

> 6,500 nmol/d highly suggest

~ 90% specific

VMA: unacceptably high false negative rate (41%)

Plasma CA Urine CA + MN Plasma MN

Very sensitive (97-99%)

Specificity is low (82%)

except in hereditary syndromes (96%)

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?

A 72 y.o. male with Colon ca and an adrenal mass

Patient on treatment with Sinemet for Parkinson

Interference

Westphal: Am J Med Sci, Volume 329(1).January 2005.18-21

DRUGS

• Acetaminofen

•Benzodiazepines

•Buspirone

•Diuretics

•Levodopa

•Sympathomimetics

•TCA

•Vasodilators

•Tetracycline and quinidine

•Ethanol

FOODS AND OTHERS

•Bananas (NE)

•Caffeine

•Nicotine

•Exercise

An 82 y.o. male 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: E 25 (-136); NE 3678 (-591) MN 645 (281-1841); NMN 21740 (502-2531)

Why are some PHEO patients normotensive despite high circulating cathecolamines?

Chronically hypovolemics

Increase production of vasodilator agents

(DOPA acting in the CNS; dopamine acting on

mesenteric and renal vessels; prostaglandins)

Adrenergic desensitization: down-regulation of

alpha-1 receptors

Polymorphism in beta-2 receptors that allows

continued b2-mediated vasodilation

Can radiology help?

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 <40Early washout - 50% at 5min -70% at 15min

High enhancemtSlow washout -8% at 5 min; -20% at 15 min

Inhomogeneous b/o areas of necrosis

Slow washout> 40 HU at 30 min

Signal Intensity

(c/c liver)

Isointense on T1&T2

Hypointense on T1

Hyperintens on T2

Hyper or Iso on T2 Mets can be isointense

Enhancement Mild Rapid and marked Variable

Wash-out Rapid Slow Slow

Chemical Shift Imaging (CSI) 

Bright on “in-phase” images

Low signal on “out-of-phase” ima

MR

I C

T

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 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: 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)

Medical Therapy CCB:

Nicardipine, Amlodipine, Nifedipine or verapamil Advantages: better tolerated, less perioperative fluids, fast

and effective during paroxysms, in vitro nifedipine reduces proliferation of pheo cells

Alpha-adrenergic blockade Phenoxybenzamine: start 10 mg/day, increase q3d to 30-

60 mg/d 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 Advantages: short acting (prazosin< doxazosin), less reflex

tachy, less post-op hypotension

Medical Therapy

ACE inhibitors and ARBs CA ^ renin etc Pheos have ACE binding sites Should not be use as sole agent

Beta blockers Only after alpha-blockade or CC blockade Metoprolol, labetalol, propranolol

Metyrosine 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

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ANSWER

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YOUR ANSWERYOUR ANSWERIS CORRECT!!!IS CORRECT!!!YOUR ANSWERYOUR ANSWERIS CORRECT!!!IS CORRECT!!!

Pathophysiologic & Clinical Manifestations of CA Excess1

Target Tissue Physiologic Effect Pathophysiologic Manifestations Clinical Manifestations

Heart Increased heart rate Tachycardia PalpitationsTachyarrhythmia Angina pectoris

Increased contractility Increased myocardial O2 consumption 

Angina pectoris

Myocarditis Congestive heart failureCardiomyopathy  

Blood vessels Arteriolar constriction Hypertension HeadacheCongestive heart failureAngina pectoris

Venoconstriction Decreased plasma volume DizzinessOrthostatic hypotensionCirculatory collapse

Gut Intestinal relaxation Impaired intestinal motility IleusObstipation

Pancreas (B cells) Suppression of insulin release

Carbohydrate intolerance HyperglycemiaGlucosuria

Liver Increased glucose output Carbohydrate intolerance HyperglycemiaGlucosuria

Adipose Lipolysis Increased free fatty acids Weight lossSkin (apocrine glands) Stimulation Sweating DiaphoresisBladder neck Contraction Elevated urethral pressures Urinary retentionMost tissues Increased basal metabolic

rateIncreased heat production Heat intolerance

SweatingWeight loss

1Modified, with permission, from Werbel SS, Ober KP: Pheochromocytoma: Update on diagnosis, localization, and management. Med Clin North Am 1995;79:131.