Transcript Dr Rivera
Internal Medicine Residents Rounds Juan Rivera, MD Pheochromocytomas Rare tumors Pheos should be suspected, confirmed, localized, and resected because: 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? 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 Pheo Carcinoid Perspiration Palpitation Pain Pallor Pressure Flushing Abdo pain: Intermittent intestinal obstruction or ischemia Diarrhea Bronchospam Hypotension or rarely Mastocytosis Plethora of manif: 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. Rarely: 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 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 Other causes of spells Endocrine: Anxiety & panic attacks Somatization disorders Miscellaneous: Labile essential HTN Renovascular disease Angina Psychiatric: Polycytemia Vera Pharmacologic Thyrotoxicosis Menopausal syndrome Medullary thyroid ca Hypoglycemia Cardiovascular: 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 Plasma CA 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 > 6,500 nmol/d highly suggest ~ 90% specific Medications, food, stress 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? A 72 y.o. male with Colon ca and an adrenal mass 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 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? 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 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 3060 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 Beta blockers 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 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.