This document discusses the diagnosis and management of pheochromocytoma. Key points include: - Pheochromocytomas are rare catecholamine-secreting tumors that can cause hypertension. Diagnosis involves measuring plasma or urine metanephrines and imaging tests. - Preoperative management aims to control blood pressure and prevent hypertensive crises during surgery. This involves alpha-blockade using drugs like phenoxybenzamine for 1-2 weeks before surgery. - Surgery is the main treatment and involves an experienced multidisciplinary team. For inoperable or malignant tumors, nuclear medicine treatments or lifelong medical management may be used. Close postoperative monitoring is important.

1. PHEOCHROMOCYTOMA-
MANAGEMENT
Dr Karthik Balachandran

2. AGENDA
 Introduction
 Diagnosis
 Management
 Preop
 Intraop
 Postop and follow up
 Special situations

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. CATECHOLAMINE SYNTHESIS

5. CATECHOLAMINE METABOLISM

7. 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)

8. • 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)

9. DIAGNOSTIC ALGORITHM

10. 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

11. 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

13. 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)

14. 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)

15. 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

16.  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

17. 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

19. 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

20. CHEMICAL SHIFT MRI

21. 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

22. NUCLEAR IMAGING

25.  111Indium-pentreotide
 Some pheo have somatostatin receptors
 PET

18F-fluorodeoxyglucose (FDG)-in advanced cases
 6-[18F]-fluorodopamine- excellent sensitivity

26. 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

27. PREOP WORKUP
 CBC, electrolytes, creatinine, INR/PTT
 CXR
 EKG
 Echo (r/o DCM )

28. 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!

29. 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

30. 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)

31. 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)

32. PREOP: + BLOCKADE
 If BP still not cntrl despite + blockade
 Add Prazosin to Phenoxybenzamine
 Add CCB, ACE-I
 Avoid diuretics as already ECFv contracted
 Metyrosine

33. 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

34. 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. 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