This document discusses pheochromocytoma, including its epidemiology, clinical presentation, diagnosis, and management. Key points include: Pheochromocytomas are rare neuroendocrine tumors that secrete excess catecholamines. Common symptoms include headaches, sweating, palpitations, and hypertension. Diagnosis involves biochemical testing of urine or plasma catecholamines/metabolites and imaging such as CT, MRI, or MIBG scan. Preoperative management focuses on alpha- and beta-blockade to control blood pressure and symptoms prior to surgical resection.

1. Speaker: Dr.Kumar
Moderator : Dr. Prabhavati
Pheochromocytoma

3. Pheochromocytoma
1. Catecholamine Physiology/Pathophysiology
2. Clinical Presentation
1. Epidemiology
2. Signs & Symptoms
3. Diagnosis
1. Biochemical
2. Localization
4. Management
1. Preoperative
2. Operative
3. Postoperative
4. Pregnancy

4. Catecholamine Producing Tumors
Neural Crest
Sympathoadrenal Progenitor Cell
(Neuroblasts)
Chromaffin Cell Sympathetic Ganglion Cell
Intra-adrenal Extra-adrenal
Pheochromocytoma
Ganglioneuroma
Neuroblastoma

5. Catecholamine Producing Tumors
Pheochromocytoma
Paraganglioma (extra-adrenal pheo)
Ganglioneuroma
Neuroblastoma
Cheodectoma
Glomus jugulare tumor

6. HISTORY
First recognised by Von Frankel
Pheochromocytoma= dusky colored tumor
Name coined by Pick in 1912
Successful surgery for excision of tumor- Roux & Mayo
( 1926-27)

7. Pheochromocytoma
Neuroendocrine tumour of the medulla of the adrenal
glands
Originates from the chromaffin cells along the
paravertebral sympathetic chain extending from pelvis to
base of skull
>95% are abdominal
>90% in adrenal medulla
Secretes excessive amounts of adrenaline and
noradrenaline
80% occur unilateral

8. Pheo: ‘Rule of 10’
10% extra-adrenal (closer to 15%)
10% occur in children
10% familial (closer to 20%)
10% bilateral or multiple (more if familial)
10% recur (more if extra-adrenal)
10% malignant
10% discovered incidentally

9. Tyrosine L-Dopa Dopamine
Norepinephrine
Epinephrine
Catecholamines
Normetanephrine
Metaneprine
PNMT
DBH
COMT
COMT
Metabolites
Homovanillic acid
(HVA)
MAO, COMT
Vanillymandelic Acid
(VMA)
MAO
MAO
TH
phenylethanolamine N
-methyltransferase - PNMT
dopamine β-hydroxylase -DBH

10. Tumor Secretion:
 Large Pheo: more metabolites
 (metabolized within tumor before release)
 Small Pheo: more catecholamines
 Sporadic Pheo: Norepi > Epi
 Familial Pheo: Epi > Norepi
 Paraganglioma: Norepi
 Cheodectoma, glomus jugulare: Norepi
 Gangioneuroma: Norepi
 Malignant Pheo: Dopamine, HVA
 Neuroblastoma: Dopamine, HVA

11. Adrenergic Receptors
Alpha-Adrenergic Receptors
α1: vasoconstriction, intestinal relaxation, uterine
contraction, pupillary dilation
α2: ↓ presynaptic NE (clonidine), platelet aggregation,
vasoconstriction, ↓ insulin secretion
Beta-Adrenergic Receptors
β1: ↑ HR/contractility, ↑ lipolysis, ↑ renin secretion
β2: vasodilation, bronchodilation, ↑ glycogenolysis
β3: ↑ lipolysis, ↑ brown fat thermogenesis

12. Pheochromocytoma
1. Clinical Presentation
1. Epidemiology
2. Signs & Symptoms

13. Pheochromocytoma
0.01-0.1% of HTN population
Found in 10% of those screened
M = F
3rd
to 10th
decades of life
Rare, investigate only if clinically suspicion:
Signs or Symptoms
Severe HTN, HTN crisis
Refractory HTN (> 4drugs)
HTN present @ age < 20 or > 50 ?
Adrenal lesion found on imaging (ex. Incidentaloma)

14. Pheo: Signs & Symptoms
The five P’s:
Pressure (HTN) 9%
Pain (Headache) 80%
Perspiration 71%
Palpitation 64%
Pallor 42%
o Paroxysms (the sixth P!)
The Classical Triad:
Pain (Headache), Perspiration, Palpitations
Lack of all 3 virtually excluded diagnosis of pheo

15. Hypertension – commonest presenting complaint
Paroxysmal
episodic

16. Pheo: Paroxysms, ‘Spells’
10- 17%
10-60 min duration
Frequency: daily to monthly
Spontaneous
Precipitated:any activity that displaces abdominal contents
Diagnostic procedures, I.A. Contrast
Drugs (opiods, unopposed β-blockade, anesthesia induction,
histamine, ACTH, glucagon, metoclopramide)
Strenuous exercise, movement that increases intra-abdo
pressure (lifting, straining)
Micturition (bladder paraganlgioma)

17. Pheo: Paroxysms, ‘Spells’
Sym depend upon the relative proportion of epi &
norepi
Excessive secretion of epi & dopamine
Due to epinephrine:
Headache, profuse sweating, palpitations, apprehension
often with a sense of impending doom
Pallor/flushing d. t peripheral adrenergic response
Due to dopamine:
Nausea & vomiting d .t. vasodilation in the GIT

18. Pheo: Hypotension!
Hypotension (orthostatic/paroxysmal) occurs in many
patients
Mechanisms:
ECF contraction
Loss of postural reflexes due to prolonged catecholamine stimulation
Tumor release of adrenomedullin (vasodilatory neuropeptide)

19. Cardiac manifestations
Sinus tachy, bradycardia , SVT, ventricular ectopics, V
tach
Catecholemine induced inc. myocardial oxygen
consumption, coronary vasospasm
Angina/MI
Cardiomyopathy- hypertrophic Cardiomyopathy- diastolic dysfn-
norepi induced
Dilated cardiomyopathy- systolic dysfn- epi induced
 CCF with myocarditis
 concentric hypertrophy/ assymetrical hypertrophy
Rarely sinus node dysfunction

20. Neurologic manifestations
Hypertensive encephalopathy ( altered mental status,
focal neurological s/s, seizures )
Stroke – due to cerebral infarction/ embolus
Intracerebral bleed

21. Pheo: Signs (metabolic)
 Hypercalcemia
 Associated MEN2 HPT
 PTHrP secretion by pheo
 Mild glucose intolerance- supression of insulin secretion,
glycogenolysis ( norepinephrine)↑
 Epi causes stimulation of insulin release through B2
adrenoceptars- this is offset by the effects of circulation
norepinephrine
 polyuria
 Lipolysis- increased epinephrine secr
 Weight-loss
 Ketosis > VLDL synthesis (TG)

22. Familial Pheo
MEN 2a
50% Pheo (usually bilateral)+ medullary Ca Thyroid +
hyperparathyroidism
MEN 2b
50% Pheo (usually bilatl) mucosal neuroma, marfanoid
habitus
Von Hippel-Landau
50% Pheo (usually bilat), retinoblastoma, cerebellar
hemangioma, nephroma, renal/pancreas cysts

23. Familial Pheo
NF1 (Von Recklinghausen's)
2% Pheo (50% if NF-1 and HTN)
Café-au-lait spots, neurofibroma, optic glioma
Familial paraganglioma
Familial pheo & islet cell tumor
Other:
1. Tuberous sclerosis,
2. Sturge-Weber,
3. ataxia-telangectgasia,
4. Carney’s Triad (Pheo, Gastric Leiomyoma, Pulm chondroma)

24. Pheochromocytoma
Diagnosis
1. Biochemical
2. Localization

25. 24h Urine Collection
Positive results (> 2-3 fold elevation):
24h Ucatechols > 2-fold elevation
24h Utotalmetanephrines > 1.2 ug/d
24h UVMA > 3-fold elevation
Detected by high performance liquid chromatography

26. 24h Urine Collection
Test Characteristics:
24h urinary catechol Sen 83% Spec 88%
24h U total metanephrines Sen 76% Spec 94%
24h Ucatechols + Utotalmetanephrines Sen 90% Spec 98%
24h UVMA Sen 63% Spec 94%
Sensitivity increased if 24h urine collection begun at onset of a
paroxysm
Serum creatinine measured for all collections of urine to
determine adequacy of collection

27. Plasma free metanephrines sen 99%
spec 89%
Plasma catecholamines sen 84%
spec 81%

28. Biochemical Tests: Summary
SEN SPEC
Ucatechols 83% 88%
Utotal metanephrines 76% 94%
Ucatechols+metaneph 90% 98%
UVMA 63% 94%
Plasma catecholamines 85% 80%
Plasma metanephrines 99% 89%

29. 24h Urine: False Positive
Drugs: TCAs, MAO-i, levodopa, methyldopa, labetalol,
propanolol, clonidine (withdrawal), ilicit drugs (opiods,
amphetamines, cocaine), ethanol, sympathomimetics (cold
remedies)
Hold these medications for 2 weeks!
Major physical stress (hypoglycemia, stroke, raised ICP, etc.)

30. Plasma Catecholamines
Plasma total catechols > 2000 pg/mL
SEN 85% SPEC 80%
False positives: same as for 24h urine testing, also with diuretics,
smoking

31. Suppression/Stimulation Testing
Clonidine suppression
Usually they decrease catecholamines
Unlike normals, pheo patients won’t suppress their
plasma norepi with clonidine
Glucagon stimulation
May precipitate hypertensive crisis
Pheo patients, but not normals, will have a > 3x
increase in plasma norepi with glucagon

32. Localization: Imaging
90% adrenal,
Extra- adrenal sites- organ of Zuckerlandl, bladder, myocardium,
mediastenum, carotid & glomus jugulare bodies
CT abdomen
Adrenal pheo SEN 93-100%
Extra-adrenal pheo SEN 90%
MRI
> SEN than CT for extra-adrenal pheo
MIBG Scan
SEN 77-90% SPEC 95-100%

34. MIBG Scan
123
I or 131
I labelled metaiodobenzylguanidine
Saved for cases where pheo diagnosed biochemically but no
tumor on CT/ MRI
MIBG catecholamine precurosr taken up by the tumor
Inject MIBG, scan @ 24h, 48h, 72h
False negative scan:
Drugs: Labetalol, reserpine, TCAs, phenothiazines
Must hold these medications for 4-6 wk prior to scan

36. Pheochromocytoma
1. Management
1. Preoperative
2. Operative
3. Postoperative
4. Pregnancy

37. Pheo 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 preparation, α-blockade
New anesthetic techniques
o Anesthetic agents
o Intraoperative monitoring: arterial line, EKG monitor,
CVP line, Swan-Ganz
Experienced & Coordinated team:
Endocrinologist, Anesthesiologist and Surgeon

38. Preop W/up
CBP, electrolytes, creatinine, INR/PTT
CXR
ECG
Echo (dilated CMY 2º catechols)

39. Preop Preparation Regimens
Combined α + β blockade
Phenoxybenzamine
Selective α1-blocker (ex. Prazosin)
Propanolol
Metyrosine
Calcium Channel Blocker (CCB)
Nicardipine

40. Preop: α + β blockade
Start at least 10-14d preop
Allow sufficient time for ECF re-expansion
Phenoxybenzamine
Drug of choice
Covalently binds α-receptors (α1 > α2)
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)

41. Phenoxybenzamine (cont’d)
Side-effect: orthostasis with dosage required to normalized seated BP,
reflex tachycardia
Drawback: periop hypotension/shock unlikely to respond to pressor
agents.
Causes presynaptic inhibition of adrenergic control thus leading to inc in
beta adrenergic outflow
Thus beta blockers needed to be given alongside

42. Evaluation of α adrenergic
blockade
Roizens criteria
Arterial BP < 160/95 mm Hg in the last 48 hrs prior to
surgery. Recommended to measure in stressful environment
Mild orthostatic hypotension indicates optimal α adrenergic
blockade but not < 80/45.
ECG- free of ST changes for > 2 wks
Ventricular ectopic < 1 over 5 min

43. Preop: α + β blockade
β-blockade
Used to control reflex tachycardia and prophylaxis against
arrhythmia during surgery
Start only after effective α-blockade (may ppt HTN)
If suspect CHF/dilated CMY  start low dose
 Propranolol Dose
o Start 40 mg po bid  increase to cntrl HR
o Up to 480 mg/day in divided doses
o IV 1-2 mg bolus

44. Beta adrenergic blockers
Propronolol ( contd)
Side effects- may induce cardiac failure, bronchospasm
Oral bioavailability 25% (extensive 1st
pass metabolism)
Atenolol- selective B1
Dose 50- 100 mg/d PO
Max 300 mg/d
IV 2.5 to 10 mg/d

45. Beta adrenergic blockers
Esmolol – selective B1 for rapid intraop BP control
Bolus IV 250-500 µ/kg/min
Infusion 25 to 250 µ/kg/min
Labetolol –mixed +ɑ Ɓ
Dose- 50- 200 mg/d PO
IV 0.25 mg/kg
Not used as asole drug due to unpredictable control of BP

46. Preop: α + β blockade
If BP still not cntrl despite α + β blockade
Add Prazosin to Phenoxybenzamine
Prazosin (Minipress) –competitive, selective α1 blockade
 T1/2- 2-3 Hrs
Dose -1-5 mg PO BD
Side effects- postural hypotension reflex tachycardia
No β blockade required
Not routinely used as incomplete α-blockade
Used more for long-term Rx (inoperable or malignant pheo)
Other selective α1 blockers- terazosin, doxazocin

47. Other antihypertensives
CCB-
Diltiazem 60- 120mg/d, max 360mg/d
T1/2- 3to 5 hrs
Side effects- bradycardia, exacerbates cardiac failure
Nifedepine – 30mg/d PO Max. 360mg/d
T1/2-1 to 2 hrs
Side effects- hypotension, peripheral edema
 ACE-I- Ramipril
Avoid diuretics as already ECF contracted

48. Preop: CCB
Nicardipine
Started po 24h to few weeks preop to cntrl BP and allow ECF restoration
After intubation  IV Nicardipine gtt (start 2.5 ug/kg/min)
IV Nicardipine adjusted to SBP
Stopped prior to ligation of tumor venous drainage
Tachycardia Rx with concurrent IV esmolol
Advantage: periop hypotension may still respond to pressor
agents as opposed to those patients who are completely α-blocked

49. Preop: α + β blockade
Meds given on morning of surgery
Periop HTN:
IV phentolamine (Regitine)
Short acting non-selective α-blocker
IV Nitroprusside (NTP)
Periop arrhythmia: IV esmolol
Periop Hypotension: IV crystalloid +/- colloid

50. Pheo: Rx of HTN Crisis
IV phentolamine
IV NTP
IV esmolol
IV labetalol – combined α + β blocker

51. Preop: Metyrosine (Demser)
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 α + β blockade or other preop prep
Tyrosine L-Dopa Dopamine
Norepinephrine
Epinephrine
PNMT
DBH
TH

52. O.R.
Admit night before for overnight IV saline
Arterial line, EKG monitor, CVP line
Known CHF, CAD, low EF(<30): consider Swan-Ganz
Spo2, ETCO2, temperature monitoring
preop medications:
Anxiolytic sedative- benzodiazepine helps dec catecholamines
release
Opoids- morphine preferably avoided as causes histamine
release
Fentanyl, sufentanyl safe

53. Premedication
Atropine or Glyco pyrolate to be omitted- causes tachycardia
Droperidol- antiemetic, blocks α adrenoceptor and inhibit
catecholamine uptake & promotes catecholamine release

54. Anaesthetic technique
General anaesthesia
Regional anaesthesia- mid to low thoracic
Combined regional and general anaesthesia
Preferred- combined regional and general anaesthesia technique
Here although regional anaesthesia protects against stresses of
surgery, it cannot prevent catecholamine surges due to tumor
manipulation.
In extensive sympathetic blockade, severe hypotension after
tumor removal,

55. INDUCTION
Essentially imp to give induction agents slowly along with close
monitoring of HR and arterial pressure
Thiopentone / propofol widely used
Etomidate –causes pain/ involuntary movement
Ketamine – not recommended
Multimodal – benzodiazapines+ opoid+ induction agent

56. Attenuate pressor response
Important for laryngoscopy and tracheal intubation
2% lignocaine – 1-1.5mg/kg
Esmolol – 50- 100 µg/kg/min
During laryngoscopy catecholamine levels ↑
Normally- 200- 2000 pg/ml
In pheo- 2000- 20,000 pg/ml

57. Neuromuscular blockade
Non depolarising neuromusc blocking drugs
DOC-Vecuronium
Suxamethonium- avoided causes fasciculations and rise in
intra abdominal pressure
Atracurium/ mivacurium- best avoided d. t release of
histamine
Cisatracurium/ rocuronium- safe cardio stable and least
histamine release

58. maintenance
Inhalational agent- isoflurane used extensively coz does not
sensitize the myocardium to catecholamines
Halothane undesirable ……arrhythmogenic properties
Sevoflurane used successfully (fast onset …..fast offset)

59. O.R
Have ready: IV phentolamine, IV NTP, IV esmolol
Other alternatives tried- MgSO4 ,40-60 mg/kg bolus foll by 2
gms/hr
Very high uncontrolled BP- surgeons to stop
Ligation of adrenal vein- sudden hypotension
Rx hypotension with crystalloid +/- colloid 1st
may need dopamine/ noradrenaline/ phenylephrine
Aim for CVP 12 or Wedge 15
Inotropes may not work!

60. Adverse perioperative effects
Large tumor size
Prolonged duration of surgery
Inc levels of preoperative urinary catecholamines and
catecholamine metabolites

61. Laparoscopic adrenalectomy.
If tumor < 8cm
Slow CO2 insufflation….. Not > 12 mm Hg

62. Postop
Post op ventilation / ICU stay- depends upon the
haemodynamic status…. Preferably ICU stay for 24 hrs
Hypoglycemia post op due to disinhibition of B cell
supression….. Increased insulin secretion
Glucose supplementation at end of surgery

63. Post op
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
5 yr survival- non malignant pheo- 95%
Malignant- < 50 %

64. Pheo: Unresectable, Malignant
α-blockade
Selective α1-blockers (Prazosin, Terazosin, Doxazosin) 1st
line as less side-effects
Phenoxybenzamine: more complete α-blockade
β-blocker
CCB, ACE-I, etc.
Nuclear Medicine Rx:
Hi dose 131
I-MIBG or 111
indium-octreotide depending on MIBG
scan or octreoscan pick-up
Sensitize tumor with Carboplatin + 5-FU

65. Pheo & Pregnancy
Grave prognosis ,mortility: maternal - 48%, fetal 55%
Diagnosis with 24h urine collections and MRI
No stimulation tests, no MIBG if pregnant
Never spontaneous labour
1st
& 2nd
trimester (< 24 weeks):
Phenoxybenzamine + βblocker prep
Resect tumor laprascopically
3rd
trimester:
Phenoxybenzamine + βblocker prep…..2-3 wks
When 37 weeks: cesarian section followed by tumor resection

66. Conclusion
Long term outlook very good
Managed by an experienced team of anaesthesiologist, surgeon,
endocrinologist &cardiologist
Principles of anaesthetic management
Good adrenergic blockade preop
Vigilent intraop monitoring and treatment of hyper/
hypotension
Post op ICU care
Antihypertensive for a prolonged period

67. THANK YOU