Pheochromocytoma management

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Presentation detailing the management of Pheochromocytoma

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Pheochromocytoma management

  1. 1. PHEOCHROMOCYTOMA- MANAGEMENT Dr Karthik Balachandran
  2. 2. AGENDA  Introduction  Diagnosis  Management  Preop  Intraop  Postop and follow up  Special situations
  3. 3. INTRODUCTION  Catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla  Term coined by Pick in 1912  To be distinguished from paraganglioma  Risk of malignancy  Other neoplasms  Genetic testing
  4. 4. CATECHOLAMINE SYNTHESIS
  5. 5. CATECHOLAMINE METABOLISM
  6. 6. CLINICAL SUSPICION Pheochromocytoma should be suspected in patients who have one or more of the following: • Hyperadrenergic spells (e.g., self-limited episodes of nonexertional palpitations, diaphoresis, headache, tremor, or pallor) • Resistant hypertension • A familial syndrome that predisposes to catecholamine- secreting tumors (e.g., MEN2, NF1, VHL)
  7. 7. • A family history of pheochromocytoma • An incidentally discovered adrenal mass • Hypertension and diabetes • Pressor response during anesthesia, surgery, or angiography • Onset of hypertension at a young age (<20 years) • Idiopathic dilated cardiomyopathy • A history of gastrointestinal stromal tumor or pulmonary chondromas (Carney triad)
  8. 8. DIAGNOSTIC ALGORITHM
  9. 9. BIOCHEMICAL DIAGNOSIS  Measurement of metabolites better(intratumoral metabolism)  Plasma free metanephrines –screening test  Absolute value important*  Can be used in renal failure patients also(level-3 fold)  Precautions for taking blood sample *Sawka AM, Prebtani AP, Thabane L, et al. A systematic review of the literature examining the diagnostic efficacy of measurement of fractionate plasma free metanephrines in the biochemical diagnosis of pheochromocytoma. BMC Endocr Disord. 2004;4:2
  10. 10. PRECAUTIONS  Stop all interfering drugs  Patients lying supine for at least 20 minutes before sampling  Sample through previously inserted iv line  Avoid alcohol and nicotine x 12 hrs  Preferably after an overnight fast  Important for diagnostic cut offs (metanephrine, <0.3 nmol/L; normetanephrine, <0.66 nmol/L) Lenders JW, Keiser HR, Goldstein DS, et al. Plasma metanephrines in the diagnosis of pheochromocytoma. Ann Intern Med. 1995;123: 101-109
  11. 11. URINE OR PLASMA? Test Sensitivity Specificity 24 hr urine fract metanephrines 98% 98% Plasma frac metanephrines 96-100% 85-89% 77%* *older than 60 years Plasma : •High negative predictive value •In children •In dopamine secreting tumors( plasma methoxy tyramine better than urinary dopamine/dihydroxyphenylalanine)
  12. 12. DIAGNOSTIC CLUE  Large Pheo: more metabolites  (metabolized within tumor before release) • Small Pheo: more catecholamines • Sporadic Pheo: Norepi > Epi • Familial Pheo: Epi > Norepi • Epinephrine in MEN2 and norepinephrine in VHL(due to expression of PNMT)
  13. 13. CLONIDINE SUPPRESSION TEST  Not in all cases-confirmatory  To tackle false positives  centrally acting α2- agonist that normally suppresses the release of catecholamines from neurons but does not affect the catecholamine secretion from a pheochromocytoma
  14. 14.  0.3 mg clonidine- measure catecholamines and metanephrines before and 3 hr after  Positive if  Norepinephrine + epinephrine <500 pg/ml or >50% decrease in norepinephrine  Plasma normetanephrine 40% reduction
  15. 15. LOCALISATION  CT or MRI is the initial localisation test  Sensitivity >95%; specificity >65%  Imaging phenotype  CT enhancement,slow washout  Variable size(average 4.5 cm)  Bilaterality  cystic and hemorrhagic changes  high signal intensity on T2-weighted MRI
  16. 16. NEWER MODALITY  Chemical shift MRI  Principle : hydroegen protons in water and lipid resonate at different frequencies  Pheo –low lipid  In phase vs out of phase  Benign adenomas lose signal in out of phase techniques
  17. 17. CHEMICAL SHIFT MRI
  18. 18. NUCLEAR IMAGING  Indications  Negative abdominal imaging  Pheo >10 cm  Paragangliomas  123I-MIBG is superior to 131I-MIBG  Inject MIBG, scan @ 24h, 48h, 72h  Lugol’s 2 drops tid x 9d (from 2d prior until 7d after MIBG injection to protect thyroid)  False negative scan:  Drugs: Labetalol, reserpine, TCAs, phenothiazines  Must hold these medications for 4-6 wk prior to scan
  19. 19. NUCLEAR IMAGING
  20. 20.  111Indium-pentreotide  Some pheo have somatostatin receptors  PET  18F-fluorodeoxyglucose (FDG)-in advanced cases  6-[18F]-fluorodopamine- excellent sensitivity
  21. 21. MANAGEMENT  Prior to 1951, reported mortality for excision of pheochromoyctoma 24 - 50 %  HTN crisis, arrhythmia, MI, stroke  Hypotensive shock  Currently, mortality: 0 - 2.7 %  Preoperative preperation, -blockade?  New anesthetic techniques?  Anesthetic agents  Intraoperative monitoring: arterial line, EKG monitor, CVP line, Swan-Ganz  Experienced & Coordinated team:  Endocrinologist, Anesthesiologist and Surgeon
  22. 22. PREOP WORKUP  CBC, electrolytes, creatinine, INR/PTT  CXR  EKG  Echo (r/o DCM )
  23. 23. PREOP PREPERATION REGIMENS  Combined + blockade  Phenoxybenzamine  Selective 1-blocker (ex. Prazosin)  Propanolol  Metyrosine  Calcium Channel Blocker (CCB)  Nicardipine  No Randomized Clinical Trials to compare various regimens!
  24. 24. PREOP: + BLOCKADE  Start at least 10-14d preop  Allow sufficient time for ECFv re-expansion  Phenoxybenzamine  Drug of choice-western literature  Covalently binds -receptors ( 1 > 2)  Start 10 mg po bid  increase q2d by 10-20 mg/d  Increase until BP cntrl and no more paroxysms  Maintenance 40-80 mg/d (some need > 200 mg/d)  Salt load: NaCl 600 mg od-tid as tolerated
  25. 25. PREOP: + BLOCKADE  Phenoxybenzamine (cont’d)  Side-effect: orthostasis with dosage required to normalized seated BP, reflex tachycardia  Drawback: periop hypotension/shock unlikely to respond to pressor agent.  Selective 1-blockers  Prazosin, Terazosin, Doxazosin  Some experience with Prazosin for Pheo preop prep  Not routinely used as incomplete -blockade  Less orthostasis & reflex tachycardia then phenoxybenzamine  Used more for long-term Rx (inoperable or malignant pheo)
  26. 26. PREOP: + BLOCKADE  -blockade  Used to control reflex tachycardia and prophylaxis against arrhythmia during surgery  Start only after effective -blockade (may ppt HTN)  If suspect CHF/DCM  start low dose  Propanolol most studied in pheo prep  Start 10 mg po bid  increase to cntrl HR(60-80/m)
  27. 27. PREOP: + BLOCKADE  If BP still not cntrl despite + blockade  Add Prazosin to Phenoxybenzamine  Add CCB, ACE-I  Avoid diuretics as already ECFv contracted  Metyrosine
  28. 28. PREOP: + BLOCKADE  Meds given on AM of surgery  Periop HTN:  IV phentolamine  Short acting non-selective -blocker  Test dose 1 mg, then 2-5 mg IV q1-2h PRN or as continuous infusion (100 mg in 500cc D5W, titrate to BP)  IV Nitroprusside (NTP)  Periop arrhythmia: IV esmolol  Periop Hypothension: IV crystalloid +/- colloid
  29. 29. PREOP: METYROSINE  Synthetic inhibitor of Tyrosine Hydroxylase (TH)  Start 250 mg qid  max 1 gm qid  Severe S/E’s: sedation, extrapyramidal, diarrhea, nausea/vomit, anxiety, renal/chole stones, galactorrhea  Alone may insufficiently cntrl BP and reported HTN crises during pheo operation  Restrict use to inoperable/malignant pheo or as adjunct to + blockade or other preop prep Tyrosine L-Dopa Dopamine Norepinephrine Epinephrine PNMT DBH TH
  30. 30. PHEO: RX OF HTN CRISIS  IV phentolamine-1mg iv f/b 5mg bolus/infusions  IV NTP –not more than 3 mic/kg/min  Iv nicardipine -5 mg/hour
  31. 31. ANESTHESIA AND SURGERY  Α-and β-adrenergic blockers can be administered early in themorning on the day of the operation  Avoid fentanyl,ketamine,morphine,desflurane,halothane  Preferred induction- propofol/etomidate  Laparascopy for <8cm tumor
  32. 32. POSTOP  Most cases can stop all BP meds postop  Postop hypotension: IV crystalloid  HTN free: 5 years 74% 10 years 45%  24h urine collection 2 wk postop  Surveillance:  24h urine collections q1y for at least 10y  Lifelong f/up
  33. 33. PERSISTENT HTN  Accidental ligation of a polar renal artery, resetting of baroreceptors  Hemodynamic changes  Structural changes of the blood vessels  Altered sensitivity of the vessels to pressor substances  Functional or structural renal changes  Coincident primary hypertension
  34. 34. PHEO: UNRESECTABLE, MALIGNANT  -blockade  Selective 1-blockers (Prazosin, Terazosin, Doxazosin) 1st line as less side-effects  Phenoxybenzamine: more complete -blockade  -blocker  CCB, ACE-I, etc.  Nuclear Medicine Rx:  Hi dose 131I-MIBG or 111indium-octreotide depending on MIBG scan or octreoscan pick-up  Sensitize tumor with Carboplatin + 5-FU
  35. 35. PHEO & PREGNANCY  Diagnosis with 24h urine collections and MRI  No stimulation tests, no MIBG if pregnant  1st & 2nd trimester (< 24 weeks):  Phenoxybenzamine + blocker prep  Resect tumor ASAP laprascopically  3rd trimester:  Phenoxybenzamine + blocker prep  When fetus large enough: cesarian section followed by tumor resection

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