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Pheochromocytoma:
A Literature Review
Department of Surgery
Queen Mary Hospital
Introduction

Tumors arise from enterochromaffin cells in
adrenal medulla

Release of catecholamines and their
metabolites:


Epinephrine, norepinephrine, dopamine
Metaneprhine, normetaneprhine
Introduction
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Paragangliomas:



Abdomen – para-aortic region
Thorax
Head & neck
Thoracic Paraganglioma
Presentation
Classical symptoms:
1.



2.
3.
4.
Headache, intense & global in nature (80%)
Palpitation (64%)
Diaphoresis (57%)
Secondary hypertension
Adrenal incidentaloma
Detected by screening in patients with
predisposing syndromes
Genetic Abnormalities

Genetic mutations known to associate with
pheochromocytoma:


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VHL (von Hippel Lindau)
RET (rearranged during tranfection)
SDHB & SDHD (mitochondrial succinate
dehydrogenase enzyme complex subunit B & D)
NF1 (neurofibromin 1)
Genetic Abnormalities
Mutated gene
Locus
% malignant
RET
10q11.2
Rare
NF1
17q11.2
Rare
SDHD
11q23
Rare
SDHB
1p
50%
VHL
3p
5%
Genetic Abnormalities

Cluster 1: VHL, SDHB, SDHD
increased intracellular concentration of HIF
(hypoxia-induced factor) and angiogenesis

Cluster 2: RET, NF1
increased activation of signaling pathway
related to RNA synthesis & metabolism
Biochemical testing
Biochemical testing
1.
2.
24-hour urine catecholamines &
metanephrines
Plasma metanephrines
Biochemical testing
test
sensitivity
specificity
24 hr urine
catecholamines &
metanephrines
88%
99%
Plasma metanephrines
96%
85%
JCEM. 2003;88(10):4533-9.
Biochemical testing
Precautions:
 Measure 24-hour urinary creatinine to ensure
adequate urine sample
 Adequate rest before blood taking
 Withhold the following drugs:
Labetalol
 Tricyclic antidepressants
 Buspirone
 α-blockers, ß-blockers, diuretics, theophylline,
levodopa

Biochemical testing

Avoid the following clinical scenarios:



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
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Acute myocardial infarction
Congestive heart failure, NYHA class 3 or 4
Cerebrovascular accidents
Hypoglycaemia
Alcohol withdrawal
Other stress condition
Biochemical testing

Tests not suggested for diagnosis of
pheochromocytoma:



Plasma catecholamines
Urinary vanillylmandelic acid (VMA)
Chromogranin A
Pharmacological testing


Clonidine suppression test
Glucagon stimulation test
Localization imaging


CT
MRI
 131/123I-MIBG

(metaiodobenzylguanidine)
PET CT with different tracers
CT
Eur Radiol. 2007;17:2804-09.
CT
MRI
Eur Radiol. 2008;18:2885–92.
123I-MIBG
PET CT
 18F-FDG (18F-fluoro-2-deoxy-D-glucose)
 18F-FDA (18F-fluorodopamine)
 18F-DOPA (18F-3,4-dihydroxyphenylalanine)
 68Ga-DOTA-NOC (68Ga-[1,4,7,10-
tetraazacyclododecane-1,4,7,10-tetraacetic
acid]-1-NaI3-octreotide)
PET CT
J Clin Endocrinol Metab. 2009;94(12):4757–4767.
PET CT
MEN 2, VHL, SDHD
J Clin Endocrinol Metab. 2009;94(12):4757–4767.
PET CT
 68Ga-DOTA-NOC


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Pheochromocytoma (and paraganglioma)
also express somatostatin receptor (SSTR)
Sensitivity = 100%
Specificity = 85.7%
Accuracy = 98%
Eur Radiol. 2012 Mar;22(3):710-9.
Medical therapy

Purpose:


Control blood pressure and heart rate
Prevent intraoperative hypertensive crisis
Medical therapy

Phenoxybenzamine (POB)

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Long acting, irreversible, non-selective α-blocker
Reflex tachycardia & postoperative hypotension
Prazosin, terazosin, doxazosin
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Selective α1-blocker  no reflex tachycardia
Short acting  lower incidence of post-op
hypotension
Medical therapy
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Calcium channel blockers
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Direct arteriolar smooth muscle relaxation
No postural hypotension
Prevent coronary vasospasm & myocarditis
Use in combination with selective α1-blocker
Surgery 106:1149–1154
Is pre-op alpha-blockade
necessary?
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30% of patients received no pre-medication
No major cardiovascular complication
Surgical treatment
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
Open
Laparoscopic:

Absolute contraindications:
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Excessive cardiopulmonary risks
Relative contraindications:
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Large tumors
Severe obesity
Previous abdominal operations
Malignant tumors
Positioning for Laparoscopic
Approach
Head end
ASIS
Foot end
Head end
Xiphoid process
Costal margin
1st 12mm port
4th 5mm port
3rd 12mm port
ASIS
Foot end
2nd 12mm port
(camera)
Surgeon’s
side
Surgical treatment

Intra-operative Hemodynamic Parameters
UROLOGY 55(3):340-3
Surgical treatment

Operative Outcome
UROLOGY 55(3):340-3
Follow Up
National Comprehensive Cancer Network
(NCCN) guideline
 Every 6 months in 1st to 3rd years
 Annually after 4th year

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History & physical examination
Blood pressure
Biochemical testing
Regular imaging not suggested
Unresectable Disease

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Blood pressure and symptom control
Cytoreductive surgery
Transarterial chemoembolization (TACE)
131I-MIBG
90Y/177Lu labeled octreotide
Chemotherapy (CVD or temozolomide)
Sunitinib
Future Prospects



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Diagnostic localization technique
Genetic abnormalities
Predicting malignant potential of primary
tumour
Treatment of unresectable disease
Conclusion


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Studying the genomics of
pheochromocytoma aids early detection and
development of novel therapy.
Localization of metastatic lesions is improved
by PET CT using new tracer nuclides.
Management of pheochromocytoma require
multidiciplinary approach.
Thank you
Biochemical testing

Low risk group:



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Poorly controlled hypertension
Incidentaloma with adrenocortical phenotype
24-hr urinary catecholamines &
metanephrines
High risk group:



Personal/family history of pheochromocytoma
Predisposing syndrome
Vascular adrenal tumor on imaging
 Plasma metanephrines