Management of Pheochromocytoma the lect.ppt

We present a dangerous problem a functioning tumor of the suprarenal gland called pheochromocytoma its presentation preparation and management that is usually surgical together with the results of surgery and postoperative complications and their management Some pictures of surgery well be presented associated with the post operative follow up and post operative treatment especially if bilateral the lecture puts a schedule for the postoperative cortisol replacement therapy and how to monitor

1. Adrenal Glands
Hamed rashad
Professor of Surgery Banha University

2. Pheochromocytoma
Hamed rashad

4. Anatomy : Just above the kidneys
1.5 inches in length

5. Anatomy

6. Anatomy : Arterial supply

7. Sometimes rt adrenal vein go to the rt renal vein

8. Right gland left gland

9. CT scan of normal adrenal glands

10. Adrenal Anatomy
• small, triangular glands loosely
attached to the kidneys
• divided into two morphologically and
distinct regions
- adrenal cortex (outer)
- adrenal medulla (inner)

12. Adrenal Cortex
•Hormones produced by the adrenal cortex
are referred to as corticosteroids.
•These comprise mineralocorticoids,
glucocorticoids and androgens.
•The cortex is divided into three regions:
•zona glomerulosa
• zona fasciculata
• zona reticularis

13. Adrenal Diseases
Cushing’s Syndrome
Addison’s Disease
Conn’s (primary hyperaldo)
Adrenogenital Sydrome
Pheochromocytoma

14. Pheochromocytoma

15. Pheochromocytoma
Paroxysmal HTN
Headache
Sweating
Palpitations
Anxiety
N/V
fatigue
Visual disturbances
Facial pallor or
flushing
Cold hands/feet
hyperglycemia

16. “Rule of 10” for describimg
characteristics of Pheos
•10% are extra-adrenal
•10% occur in children
•10% are multiple or bilateral
•10% recur after surgical resection
•10% are malignant
•10% are familial
•10% of benign sporadic adrenal pheos are found
as incidentalomas

17. Hormones of the Adrenal Medulla
• adrenaline, epinephrine
• noradrenaline, norepinephrine
•80% of released catecholamines are epinephrine
•Hormone released from extraadrenl is mainly
noradrenaline

18. Anatomy and Origin
• embryologically derived from
pheochromoblasts
• differentiate into modified neuronal cells
• acts like sympathetic ganglion
• more gland than nerve
• chromaffin cells

19. MEN
MEN Type I
parathyroid tumors
pituitary tumors
pancreatic tumors
MEN Type IIa
medullary thyroid carcinoma
pheochromocytoma
hyperparathyroidism
MEN Type IIb
medullary thyroid carcinoma
pheochromocytoma
mucosal neuromas

20. 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

21. Catecholamine Synthesis
tyrosine
dihydroxyphenylalanine
dopamine
norepinephrine
epinephrine
tyrosine hydroxylase
L-aromatic amino acid decarboxylase
dopamine--hydroxylase
phenylethanolamine-N-methyltransferase

22. •Pheochromocytoma
•Paraganglioma (extra-adrenal pheo)
•Originate in extra-adrenal sympathetic chain/chromaffin tissue
•Ganglioneuroma
•Behave like paraganglioma biochemically
•Neuroblastoma
•Common malignancy in children, adrenal or sympathetic chain
•Catecholamine humoral effects usually minor
•Rapid growth & widespread metastasis
•Some differentiate and spontaneously regress
•Rx complex (surgery, XRT, chemotherapy)
Catecholamine Producing
Tumors

23. •Chemodectoma
•Carotid body, behave like paraganglioma biochemically
•Glomus jugulare tumor
•Intracranial branch of CN IX and X
•Behave like paragangliomoa biochemically
Catecholamine Producing
Tumors

24. Adrenergic Receptors
•Alpha-Adrenergic Receptors

1: vasoconstriction, intestinal relaxation, uterine
contraction, pupillary dilation

2
: platelet aggregation vasoconstriction,
 insulin secretion
•Beta-Adrenergic Receptors

1:  HR/contractility,  lipolysis,  renin secretion

2: vasodilation, bronchodilation,  glycogenolysis

3:  lipolysis,  brown fat thermogenesis

25. Adrenal
and
extraadren
al pheo :
Sympathetic
paraganglionic cells
from skull base to
bladder=
parpgangliomas

26. Features
•Tumor from adrenal medulla
•Rare tumor
•0.01 - .1% of hypertesives have this tumor
•Arise from chromaffin cells
•R>L
•Adrenal tumors secrete more of epinephrine
& extra-adrenal tumors secrete
norepinephrine.

27. ADRENAL MEDULLA
Pheochromocytoma

28. 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

29. Pheochromocytoma
•0.01-0.1% of HTN population
•Found in 0.5% of those screened
•M = F
•3
rd
to 5
th
decades of life

30. Pheo: Signs & Symptoms
•The five P’s:
•Pressure (HTN)90%
•Pain (Headache)80%
•Perspiration71%
•Palpitation64%
•Pallor 42%
»Paroxysms (the sixth P!)
•The Classical Triad:
•Pain (Headache), Perspiration, Palpitations
•Lack of all 3 virtually excluded diagnosis of pheo in a series of > 21,0000 patients

31. Pheo: Paroxysms, ‘Spells’
•10-60 min duration
•Frequency: daily to monthly
•Spontaneous
•Precipitated:
•Diagnostic procedures, I.A. Contrast (I.V. is OK)
•Drugs (opiods, unopposed -blockade, anesthesia induction,
histamine, ACTH, glucagon, metoclopramide)
•Strenuous exercise, movement that increases intra-abdo
pressure (lifting, straining)
•Micturition (bladder paraganlgioma)

32. Pheo: Hypotension!
•Hypotension (orthostatic/paroxysmal)
occurs in many patients
•Mechanisms:
•Extra Cellular F volume contraction
•Loss of postural reflexes due to prolonged
catecholamine stimulation
•Tumor release of adrenomedullin (vasodilatory
neuropeptide)

33. Pheo: Signs & Symptoms
•N/V, abdo pain, severe constipation (megacolon)
•Chest-pains
•Anxiety
•Angina/MI with normal coronaries:
–Catecholamine induced:  myocardial oxygen consumption or
coronary vasospasm
•CHF
•HTN  hypertrophic cardiomyopathy  diastolic dysfn.
•Catechols induce dilated cardiomyopathy  systolic dysfn.
•Cardiac dysrhythmia & conduction defects

34. Pheo: Signs (metabolic)
•Hypercalcemia
•Associated MEN2 HPT
•PTH releasing Peptide secretion by pheo
•Mild glucose intolerance
•Lipolysis
•Weight-loss
•Ketosis

35. 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

36. 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

37. Pheochromocytoma,
Diagnosis
•24hr urinary catecholamines (NE, Epi, Dop) and
metabolites (metanephrine, normetanephrine,
VMA).
•Plasma catecholamine or metabolites during
episode.
•NO FNA! (can precipitate hypertensive crisis).

38. 24h Urine Collection
•24h urine collection:
•Creatinine, catecholamines, metanephrines,
vanillymandelic acid (VMA), +/-dopamine
•HPLC with electrochemical detection or mass spect
•Positive results (> 2-3 fold elevation):
•24h U
catechols > 2-fold elevation
»ULN for total catechols 591-890 nmol/d
•24h U
total metanephrines > 1.2 ug/d (6.5 umol/d)
•24h U
VMA
> 3-fold elevation
»ULN 35 umol/d for most assays

39. Biochemical Tests: Summary
SEN SPEC
U
catechols
83% 88%
U
total metanephrines 76% 94%
U
catechols+metaneph 90% 98%
U
VMA 63% 94%
Plasma catecholamines
85% 80%
Plasma metanephrines
99% 89%

40. Pheochromocytoma,
Diagnosis
•Localizing studies: CT, MRI, MIBG scan
–Thin cut CT detects most lesions: 97%
intraabdominal.
–MRI: 90% pheos bright on T2 weighted scan
–MIBG: used for extraadrenal, recurrent,
multifocal, malignant disease.

41. Localization: Imaging
•CT abdomen
•Adrenal pheo SEN 93-100%
•Extra-adrenal pheo SEN 90%
•MRI
•> SEN than CT for extra-adrenal pheo
•PET Scan
•MIBG Scan
•SEN 77-90% SPEC 95-100%

42. MIBG Scan
•
123
I or
131
I labelled metaiodobenzylguanidine
•MIBG catecholamine precurosr taken up by the
tumor
•Inject MIBG, scan @ 24h, 48h, 72h
•Lugol’s 1 gtt tid x 9d (from 2d prior until 7d after
MIBG injection to protect thyroid)

45. Rt adrenal tumour without contrast

47. Right adrenal tumour
after contrast : vascular

49. Bilateral large adrenal tumour

50. Localization: Nuclear medicine
•MIBG
•
111
Indium-pentreotide
•Some pheo have somatostatin receptors
•PET
•
18
F-fluorodeoxyglucose (FDG)
•6-[
18
F]-fluorodopamine

51. PET scan
•Proving
malignancy

52. Malignant Lt adrenal :
a-Enhanced CT scan
b-Integrated PET-CT scan showing increased FDG uptake
c-Adrenonephrectomy showing yellowish a large adrenal mass (arrows)

53. Adrenal pheochromocytoma with increased
FDG uptake in integrated PET-CT scan

54. PHEO IN CHILDREN
•Headache/nausea/vomiting Wt loss common
•15-30 % multiple
• 24 % B/L
•10% familial
•15-30 extra adrenal
•HT is sustained
•Malignancy more common
•Polyuria/polydipsia/convulsions 25%

55. PHEO & PREGNENCY
•Present with HT/headache/palpitations
•DD…eclampsia
•Usual time of presentation….post partum---labour
•Maternal and infant mortality…high(40%)

56. 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

57. Pheo Management
•Prior to 1951, reported mortality for excision of
pheochromoyctoma 24 - 50 %
•Currently, mortality: 0 - 2.7 %
•Preoperative preperation, -blockade?
•New anesthetic techniques?
»Anesthetic agents
»Intraoperative monitoring: arterial line, EKG
monitor, CVP line, Swan-Ganz

58. Preop Work/up
•CBC, lytes, creatinine, INR/PTT
•CXR
•EKG
•Echo (r/o dilated CMY 2º catechols)

59. Preop Preperation
Regimens
•Combined  +  blockade
•Phenoxybenzamine
•Selective 
1-blocker (ex. Prazosin)
•Propanolol
•Metyrosine
•Calcium Channel Blocker (CCB)
•Norvask - Nicardipine

60. Preop:  +  blockade
•Start at least 10-14d preop
•Allow sufficient time for ECFv re-expansion
•Phenoxybenzamine
•Drug of choice
•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 tid astolerated

61. 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.

62. Preop:  +  blockade
-blockade
•Used to control reflex tachycardia and prophylaxis
against arrhythmia during surgery
•Start only after effective -blockade
•Propanolol most studied in pheo prep
»Start 10 mg po bid  increase to control HR

63. 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 Hypotension: IV crystalloid +/- colloid

64. O.R.
•Admit night before for overnight IV saline
•Arterial line, EKG monitor, CVP line
•Known CHF: consider Swan-Ganz
•Regardless of preop medications:
•Have ready: IV phentolamine, IV NTP, IV esmolol
•Rx hypotension with crystalloid +/- colloid 1
st
•Aim for CVP 12 or Wedge 15
•Inotropes may not work!

65. INTRA OPERATIVE
•Intraop…problems at time of ….induction
and handling of tumor
•Have….ECG,CVP,PCWP,output
monitoring.
•Have at hand..alpha & beta blockers loaded
IV at hand
•Phentolamine 50mg in 500ml NS
•Sodium nitroprusside 50 mg in 250ml 5%
dextrose

66. Surgical approach to right
adrenal

68. Anatomy
3rd most highly
perfused organ
(kidney, thyroid)
Within Gerota’s fascia
Cortex(80%)andmedu
lla(20%) distinct
organ, colocalized
during development

69. Anatomy
3rd most highly
perfused organ
(kidney, thyroid)
Within Gerota’s
fascia
Cortex(80%) and
medulla(20%)
distinct organ,
colocalized during
development

70. Open adrenalectomy
1- Used for cancer
operation
2- Enblock removal may
include stomach, spleen and
pancreas
3- Take periadrenal fat and
lymphatic tissue and
sometimes the kidney

71. Rt adrenalectomy : Skin
incision

73. Huge benign-looking tumour of rt
suprarenal

76. Kocherisation of the duodenum
and dissection of IVC

78. Duodenum is kocherized
to show the IVC

79. Duodenum is kocherized tg show the IVC, rt
kidney and rt adrenal beside and behind the
IVC

80. Rt adrenal with the
tumour

83. Rt adrenal vein identified &
ligated

87. Gland still attached to Zokerkandil fascia

88. Adrenal site empty (small blood clot)

89. The tumour inside the
gland

91. Abdominal wound after
closure

93. Tumour cut through

95. Laparoscopic Adrenalectomy

96. O.R.
•Anesthetic choice:
•Enflurane or isoflurane: don’t sensitized
myocardium to catecholamines
•Halothane: may sensitize heart  arrhythmia
•Laprascopic adrenalectomy if tumor < 8cm

97. Positioning

98. Port placement

99. Right
adrenalectom
y
1- Division of the
right tiangular
ligament
2- division plane
between IVC and
adrenal

100. Rt adren
•1- identify and
ligate the adrenal
vein and arteries
•2- Dissect off
diaphragm
superiorly, and
kidney inferiorly

101. Left
adrenalectom
y
•1- Mobilize spleen
and splenic flexure
•2- Leave kidney in
place
•3- Mobilize tail of
pancreas

102. Left
Adrenalectom
y
•1-Ligate vessels
•2- Dissect off
kidney and
diaphragm

104. Postoperative
•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

105. Post- Operative
•Post op 75% have normal BP and rest 25%
have easily controllable BP
•Urine catacholamines return to normal in 1
week
•Tumor recurrence seen in 10%
•Bony mets..best is bone scan
•Follow up…….since of the cases who recur
5% every year occur

106. FOLLOW UP
•Urine catacholamines
•Serum levels
•CT / MRI
•Bone scan
•MIBG

107. THANK YOU