Morning Report

1. Morning Report Rick Hobbs 4/9/08

2. Secondary Hypertension Renovascular HTN Renoparenchymal HTN Primary Aldosteronism Cushing’s syndrome Pheochromocytoma Acromegaly Hypercalcemia Oral Contraceptives Coarctation of the Aorta

3. Retroperitoneal Mass Rhabdomyosarcoma Pheochromocytoma Adrenal cortex mass Metastatic disease (particularly testicular) Renal Cell Carcinoma Lymphoma Lymphadenopathy Teratoma

4. Evaluation of Secondary Hypertension and retroperitoneal mass Serum cortisol, ACTH, 24hr urine cortisol Beta HCG, AFP Erythropoetin Plasma metaneprhines, urine catecholamines

5. PheochromocytomaPresentation Classic triad - episodic headache, sweating, and tachycardia in association with hypertension In general, those of an increased metabolic rate Angina, cardiomyopathy, dyspnea, generalized weakness Hyperglycemia - 50% have impaired carbohydrate tolerance 2/2 suppression of insulin and stimulation of hepatic glucose output, rarely requires treatment and corrects after tumor removal Elevated hematocrit 2/2 diminished plasma blood volume Orthostatic hypotension – result of diminished plasma volume and blunted sympathetic reflexes – predispose to hypotension or shock during surgery or trauma Other symptomatic presentations - Hypertensive crisis, refractory HTN, surgery difficulties, or via panic attacks, palpitations Approximately 10-50% of pheochromocytomas are diagnosed asymptomatically by CT scan. 3-10% of “incidentalomas” are pheochromocytomas, therefore 24-hour urine testing should be performed routinely.

6. PheochromocytomaDifferential Diagnosis Anxiety attacks Clonidine withdrawl Cocaine intoxication MAOI toxicity Intracranial lesions Autonomic dysfunction Other secondary HTN Complex migraine

7. PheochromocytomaDemographics Young to mid-adult life Found in only 0.2% of people w/HTN 300 people will be evaluated to find one pheochromocytoma 60% have persistently elevated HTN w/50% of these having paroxysmal hypertensive crises

8. PheochromocytomaRule of 10% 10% Bilaterally Extraadrenal Familial (bilateral, AD, 2a or 2b) Not associated with HTN Malignant often recurs in retroperitoneum and metastasizes to bone, lung Metyrosine to block tyrosine hydroxylase, aids in chronic management if resection not viable

9. Pheochromocytoma Hormonal Activity Most secrete both epi, norepi (N>E). Rarely, epi alone (assd w/MEN) Increased dopamine and homovanillic acid (HVA) is uncommon w/benign lesions, but may occur w/malignant lesions Histology stains positive for chromogranin and synaptophysin (neuroendocrine associated) Fatal paroxysms can be induced by opiates, histamine, glucagon by releasing catecholamines directly from tumor, as can drugs that block uptake of catecholamines (TCAs, SSRIs)

10. Pheochromocytoma Diagnosis Testing – biochemical confirmation before imaging Urine: 24hr catecholamines, fractionated metanephrines (sens=98%, spec=98%) TCAs, but not SSRIs should be stopped during testing Fractionated plasma metanephrines Unnecessary in most cases, can confirm if history is suggestive, but urine tests non-diagnostic Often a good first test due to 99% sensitivity, especially in certain circumstances (i.e.-kids, high risk patients [syndromes]) Spot urine collection not as sensitive, particularly in those who only have paroxysms Increased epinephrine excretion usually due to adrenal lesion Levels of metanephrines, VMA usually >3xs nl Imaging – CT or MRI both have very high sensitivity (98%), if not found with standard imaging, reconsider diagnosis, then add MIBG (which may also be used to locate metastatic foci) Percutaneous biopsy contraindicated as can induce severe paroxysm

13. PheochromocytomaAssociated Syndromes Syndromes MEN 2a – pheo, medullary carcinoma of thyroid, primary parathyroid hyperplasia MEN 2b – pheo, medullary carcinoma of thyroid, mucosal neuromas 10-25% of von Hippel-Lindau patients - phenotype includes pheochromocytoma (frequently bilateral), paraganglioma (rarely), retinal angiomas, cerebellar hemangioblastoma, epididymal cystadenoma, renal and pancreatic cysts, and renal cell carcinoma.

14. PheochromocytosisTreatment Surgical resection is key Preoperative Management – Induction of stable alpha-blockade. Phenoxybenzamine – Non-competitive alpha blocker. Titrated to blood pressure control. Given for 10-14 days prior to surgery. Prazosin, phentolamine, or selective alpha-one blockade for breakthrough paroxysms Avoid Beta-blockers during initiation of alpha blockade– will cause paradoxic increase in BP by antagonizing beta-mediated vasodilation Beta blockers often added once alpha blockade results in tachycardia to prevent tachyarrhythmias

15. PheochromocytomaSurgery Mortality <2-3% Hypertension and arrhythmias during induction, intubation, manipulation of tumor Hypotension that responds to fluids > pressors Phentolamine, nitroprusside for hypertension Propranolol for tachycardia or ectopy Metyrosine, chronic alpha (and usually beta) blockade, chemo (I-MIBG) and irradiation (though resistant) for unresectable lesions

16. PheochromocytomaOutcome 5-year survival rate after surgery 95% Complete resection cures hypertension in 75% Recurrence rate 10-16% - more likely if familial, extraadrenal or R adrenal Catecholamine excretion returns to normal in 2 weeks and should be measured to ensure complete tumor removal Measured yearly or as symptoms recur For malignant pheochromocytomas, 5-year survival <50%

17. References Paraganglioma - http://brighamrad.harvard.edu/Cases/bwh/hcache/366/full.html. Accessed 4/8/08 Harrison’s UpToDate