Post on 13-Jan-2016
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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
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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.