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1/ 
Hello #MedTwitter
This month’s @ASPNeph Renal Imaging Webinar was all about #Pheochromocytoma!
Here are a few “pheo facts” I learned!
#tweetorial #nephtwitter
Let’s start with a poll.
Which of the following is true about pheochromocytoma (PCC)?
Hello #MedTwitter This month’s @ASPNeph Renal Imaging Webinar was all about #Pheochromocytoma!
Here are a few “pheo facts” I learned!
#tweetorial #nephtwitter
Let’s start with a poll.
Which of the following is true about pheochromocytoma (PCC)?
2/Answer: D All of the above
(PMID: 24893135 & 30603807)
PCC & Paraganglioma (PGL) are catecholamine secreting tumors arising from chromaffin cells
PCC
Adrenal medulla = 80-85%
PGLExtra-adrenal =10-15% 
symp chain (abdo/chest/pelvis) or parasymp chain (head&neck)
(PMID: 24893135 & 30603807)
PCC & Paraganglioma (PGL) are catecholamine secreting tumors arising from chromaffin cellsPCC
Adrenal medulla = 80-85%PGL
Extra-adrenal =10-15% symp chain (abdo/chest/pelvis) or parasymp chain (head&neck)
3/
Many will recall the “Rule of 10s”
10% Malignant
10%
Family history
10% Bilateral
10% Extra-adrenal
But..
This rule does not hold true for children
In particular, inherited PCC/PGL more likely in children
Up to 80% in some studies! (PMID:24169644 )
Many will recall the “Rule of 10s” 10% Malignant
10%
Family history10% Bilateral
10% Extra-adrenal
But..
This rule does not hold true for childrenIn particular, inherited PCC/PGL more likely in children Up to 80% in some studies! (PMID:24169644 )
4/ Which Syndromes are associated with PGLs/PCCs?
5/Ans: D
Von Hippel Lindau: PCC (often B/L) or PGL in ~10-20%. Noradrenergic phenotype.
Gene: VHL TSG
MEN2: PCC in ~ 50%. Adrenergic phenotype.
Gene: RET
NF1: 
common ~2-3%. Usually solitary PCC.
Gene: NF1
All =AD inheritance
Source: http://UptoDate.com
Von Hippel Lindau: PCC (often B/L) or PGL in ~10-20%. Noradrenergic phenotype.Gene: VHL TSG
MEN2: PCC in ~ 50%. Adrenergic phenotype.Gene: RET
NF1: common ~2-3%. Usually solitary PCC.Gene: NF1
All =AD inheritanceSource: http://UptoDate.com
6/Many other susceptibility genes identified
Genetic mutations can be divided into 2 groups:
Genes encoding proteins
Hypoxia inducible factors: VHL, SDH, EGLN1 & HIF2A
Kinase Signalling pathway: RET, NF1, TMEM127
Genetic Testing is recommended in all children
Many other susceptibility genes identified Genetic mutations can be divided into 2 groups:
Genes encoding proteinsHypoxia inducible factors: VHL, SDH, EGLN1 & HIF2A Kinase Signalling pathway: RET, NF1, TMEM127Genetic Testing is recommended in all children
7/ Approximately how common is the classic triad of episodic headache, sweating and palpitations in children?
8/ The classic triad
has been reported in up to 54% of children (PMID: 24825268)
Average age ~ 11-13 years
M>F 2:1
Other symptoms:
anxiety weightvisual change polydipsia/uria 
glucosetremor flushing abdo pain diarrhoea pallor syncope
has been reported in up to 54% of children (PMID: 24825268)Average age ~ 11-13 yearsM>F 2:1Other symptoms:
anxiety weightvisual change polydipsia/uria glucosetremor flushing abdo pain diarrhoea pallor syncope
9/
Hypertension is common (60-90%)
Sustained > paroxysmal in children
BP can be normal
Look for abnormal ABPM eg. “non-dipping”
Orthostatic Hypotension can be a presenting feature (epinephrine secreting tumours)
(PMID: 30603807)
Hypertension is common (60-90%)Sustained > paroxysmal in childrenBP can be normal Look for abnormal ABPM eg. “non-dipping” Orthostatic Hypotension can be a presenting feature (epinephrine secreting tumours) (PMID: 30603807)
10/ Let’s Review catecholamine production & metabolism!
Catecholamines are produced by metabolism of Tyrosine DOPADopamine Norepinephrine Epinephrine
Metanephrines are the o-methylated products of catecholamine metabolism
(PMID: 30603807)
Catecholamines are produced by metabolism of Tyrosine
DOPADopamine Norepinephrine Epinephrine Metanephrines are the o-methylated products of catecholamine metabolism(PMID: 30603807)
11/ 1st line of invx is biochemical testing
Catecholamines or metanephrines can be tested
Plasma metanephrines more sens/specific than urine
Suspect false if level <3-4 x normal
Patient should be supine x 30mins for plasma sample
Use age appropriate cut-offs
Catecholamines or metanephrines can be tested Plasma metanephrines more sens/specific than urineSuspect false if level <3-4 x normal Patient should be supine x 30mins for plasma sample Use age appropriate cut-offs
12/ Which of the following medications can cause elevation of catecholamines?
13/ All the above
Sympathomimetics, SSRIs, MAO inhibitors, α/β blockersfalse catecholamines
Acetaminophen interferes w/ liquid chromatography
Stop medications ~2 wks prior to testing
If not, Clonidine suppression test
(PMID: 21615192, 28752085, 21651412)
Sympathomimetics, SSRIs, MAO inhibitors, α/β blockersfalse catecholaminesAcetaminophen interferes w/ liquid chromatographyStop medications ~2 wks prior to testingIf not, Clonidine suppression test (PMID: 21615192, 28752085, 21651412)
14/ Biochemical results can help classify the tumour:
Adrenergic: E&NE, M & NM, VMA
Noradrenergic: NE, NM, VMA
Dopaminergic: Dopamine, HVA
Adrenergic: E&NE, M & NM, VMANoradrenergic: NE, NM, VMADopaminergic: Dopamine, HVA
15/ Imaging 
localise tumour & identify mets
CT & MRI both good sens & specificity
Features can include:
attenuation on non-con CT (most >20 HU)
vascularity, cystic or hemorrhagic change
Delayed contrast washout
T2 signal on MRI
Source: http://uptodate.com
localise tumour & identify metsCT & MRI both
good sens & specificityFeatures can include:attenuation on non-con CT (most >20 HU)vascularity, cystic or hemorrhagic changeDelayed contrast washout T2 signal on MRISource: http://uptodate.com
16/ Functional imaging can be used to:
Localise tumour when CT/MRI negative
Identify metastatic/multifocal disease
Follow-up screening
Functional imaging may include integrated PET CT/MRI or scintigraphy
Let’s review some options
Localise tumour when CT/MRI negativeIdentify metastatic/multifocal diseaseFollow-up screening Functional imaging may include integrated PET CT/MRI or scintigraphy
Let’s review some options
17/ MIBG Scintigraphy:
Iobenguane I-123 is a compound similar to NE
Uptake at adrenergic tissue
Uptake in normal adrenals can by asymmetrical
Correlate with CT/MRI
PMID: 21803186
Iobenguane I-123 is a compound similar to NEUptake at adrenergic tissueUptake in normal adrenals can by asymmetricalCorrelate with CT/MRIPMID: 21803186
18/ FDG PET:
FDG is a glucose analogue
Useful in tumours with glycolytic activity
Ga68 DOTATATE PET:
Somatostatin analogue
Good uptake in well-differentiated tumours
Sensitivity & Resolution
Radiation
PMID: 19372492
FDG is a glucose analogueUseful in tumours with glycolytic activityGa68 DOTATATE PET:
Somatostatin analogueGood uptake in well-differentiated tumours Sensitivity & Resolution RadiationPMID: 19372492
19/ This helpful diagram from a comprehensive review or PCC/PGL (PMID:30603807) summarises an approach to diagnostic evaluation:
20/ Surgical removal of a PCC/PGL can trigger a life threatening catecholamine storm
This can cause:
Hypertensive Crisis
Arrhythmias
Myocardial infarction
Stroke
Also post-operatively a drop in catecholamines can lead to 
BP
Surgical removal of a PCC/PGL can trigger a life threatening catecholamine stormThis can cause:
Hypertensive CrisisArrhythmiasMyocardial infarctionStrokeAlso post-operatively a drop in catecholamines can lead to BP
21/ Aim of medical management is to prevent fluctuations in BP & post op BP
Always THINK
before 
Start with alpha blockers before beta blockers!
Initial use of beta blockers unopposed alpha action catecholamine storm
BP Always THINK
before Start with alpha blockers before beta blockers!
Initial use of beta blockers unopposed alpha action catecholamine storm
22/ There are no internationally approved protocols for management of PCC/PGLs
The table below summarises a suggested approach (PMID:30603807)
Metyrosine = tyrosine hydroxylase inhibitor 
catecholamine synthesis +/- alpha blockers can BP lability peri-op
The table below summarises a suggested approach (PMID:30603807)
Metyrosine = tyrosine hydroxylase inhibitor catecholamine synthesis +/- alpha blockers can BP lability peri-op
23/ Take home points:
PCC/PGL are rare
Only ~50% have classic symptom triad
Genetics testing for all children
Biochemistry CT/MRIFunctional imaging
Rememberbeforeto avoid a catecholamine storm!!
Thanks #ASPNeph #FellowFOAMgroup @drM_sudha @RoshanPGeorgeMD
PCC/PGL are rareOnly ~50% have classic symptom triadGenetics testing for all childrenBiochemistry CT/MRIFunctional imagingRememberbeforeto avoid a catecholamine storm!!Thanks #ASPNeph #FellowFOAMgroup @drM_sudha @RoshanPGeorgeMD
