Phaeochromocytomas (aPCA) are
chromaffin tumors arising from the
adrenal medulla and secreting CA.
90% benign, 90% adrenal, 90%
unilateral (bilateral in familial
Paragangliomas (PGL) are tumours
arising from extra-adrenal sympathetic
or parasympathetic nervous tissue.
and Ganglioma (cont.)
• Sympathetic paraganglia occur as follows: in
prevertebral, paravertebral, thoracoabdominal,
etc. They are termed extra-adrenal functional
• Parasympathetic paraganglia are located close to
major arteries and nerves, e.g., carotid body,
glomus jugulare, etc. They are termed head and
neck paraganglioma (HNPGL), and only a minority
of those shows endocrine activity (~25%).
The cells in the adrenal medulla produce
epinephrine and norepinephrine but the
extra adrenal chromaffin cells make only
PCA is found in 0.1% of patients with severe
hypertension and in less than 0.05% of all
Familial PCA may be inherited as AD trait
either alone or in combination with other
abnormalities such as multiple endocrinal
neoplasia type II.
8. Inherited syndromes
MEN type IIa and IIb: AD, RET proto-
oncogen, ch 10q.
von Hipple Lindau: occulocerebellar
angiomatosis: AD, VHL gene, ch 3p.
von Reckling Hausen disease (NF type 1):
AD, NFS 1 gene, ch 17q
Succinate dehydrogenase (SDH)
mutations: of 4 types A → D with eFPGL.
Adrenaline or noradrenaline and may be constant or episodic.
Phenylethanolamine-N-methyltransferase (PNMT) is necessary for
methylation of noradrenaline to adrenaline and is cortisol-dependent.
Paragangliomas (exception—organ of Zuckerkandl) secrete noradrenaline
only, as they lack PNMT.
Small adrenal tumours tend to produce more adrenaline whereas larger
adrenal tumours produce more noradrenaline, as a proportion of their blood
supply is direct, rather than corticomedullary, and therefore, lower in cortisol
Pure dopamine secretion is rare and may be associated with hypotension.
These tumours are more likely to be malignant.
The presence of palpitation, headaches, or sweating
in a patient with hypertension should raise the
diagnostic query of PCA.
Sweating and heat intolerance >80%.
Pallor or flushing.
Feeling of apprehension.
Hypertension: Sustained or episodic
hypertension often resistant to conventional
More commonly PCA are found incidentally
following CT imaging, thus may not show
any clinical signs and symptoms
Neurological: headache (throbbing or
constant) (65%), paraesthesiae, visual
disturbance, seizures, tremors
17. Factors that may precipitate crisis
3. Abdominal palpation
5. Drugs e.g., beta blockers, IV contrast,
anesthesia, tricyclic antidepressant,
18. Take Care
• Anxiety-panic attacks
• Other causes of hypertension =
• Diencephalic or autonomic
epilepsy (attacks of hypertension
with increased CA
Endocrine causes of excess sweating
20. Who should
1. Patients with a family history of MEN, VHL,
2. Patients with paroxysmal symptoms.
3. Young patients with hypertension.
4. Patient developing hypertensive crisis
during general anaesthesia/surgery.
5. Patients with unexplained heart failure.
6. Patients with an adrenal incidentaloma.
23. 1- 24h urine collection for
• The sensitivity of urinary VMAs is less than free
catecholamines or metadrenalines and influenced by dietary
intake and should not be used.
• Urinary metanephrines are of similar sensitivity but of
superior specificity to urinary catecholamines.
24. 2- Plasma metanephrines
• Plasma metanephrines are the most sensitive test for
detection of catecholamine excess and have only slightly
lower specificity than urinary metanephrines.
• If plasma metanephrines are borderline, urinary
metanephrines may be used for confirmation.
• Plasma catecholamines are elevated by renal failure, caffeine,
nicotine, exercise, and some drugs.
25. 3- Clonidine Suppression test
• It lowers the norepinephrine in normal persons but not in
patients with PCA.
• 300 mcg orally → failure of suppression to normal range
within 120 and 180 minutes
27. List of medications
and stimulants to
avoid before the
plasma and urinary
• Tricyclic antidepressants
• Beta-blockers: labetalol* and sotalol
• Monoamine oxidase inhibitors
• Sympathomimetics: ephedrine, pseudoephedrine,
• Stimulants: caffeine, nicotine, theophylline
• Miscellaneous: levodopa, carbidopa, alcohol, cocaine
*Labetalol interferes only with certain assays
It is easily localized (large) in
contrast to Conn’s syndrome
MRI: Bright hyperintense image on
CT: Less sensitive and specific—less
good at distinguishing between
different types of adrenal tumours.
34. What about genetic
condition? When to
1. Bilateral tumours.
2. Extra-adrenal tumour, including head and neck.
3. Age of onset (<50 years 45%).
MEN II VHL NF1
precede medullary thyroid
carcinoma in 10%).
angiomas are usually the
MRI—posterior fossa and
US of kidneys—if not
adequately imaged on MRI
Clinical examination for
café-au-lait spots and
38. 1- Medical
α-blockade must be commenced before B-blockade to avoid
precipitating a hypertensive crisis due to unopposed
It is essential that any patient is fully prepared with α- and B-
blockade before receiving IV contrast or undergoing a
procedure, such as venous sampling or surgery.
α-blockade—commence phenoxybenzamine as soon as
diagnosis made. Start at 10mg 2× day by mouth, and increase
up to 20mg 4× day (doxazosin is an accepted alternative).
39. 1- Medical (cont.)
B-blockade—use a B-blocker, such as propranolol
20–80mg 8-hourly by mouth, 48–72h after starting
phenoxybenzamine and with evidence of adequate
α-blockade (generally noted by a postural fall in BP).
Labetalol is not recommended
Treatment is commenced in hospital.
• Metyrosine (tyrosine hydroxylase
inhibitor) blocks the formation of
norepinephrine and epinephrine.
• It may be used when patients are
intolerant of the adrenergic blockers.
41. 2- Surgical
• Surgical resection is curative ≈ 75%.
• Need expert anesthetic team: tumour handling → major changes
in BP ± arrhythmias.
• Surgery may be laparoscopic if the tumour is small and apparently
42. Risk factors for haemodynamic instability
during surgery include
High noradrenaline concentration
Large tumour size
Postural drop after B-blockade, and a MAP >100mmHg
Clinical & biochemical follow up after surgery.
Cure is assessed by 24h urinary free
catecholamine measurement after 2 weeks
CA levels should be checked annually
Chromogranin A is also a useful marker
Sympathetic paraganglia occur as follows: in prevertebral, paravertebral, thoracoabdominal, in the pelvis area and close to reproductive organs, prostate, bladder, liver, and the organ of Zuckerkandl (at the bifurcation of the aorta). Tumours arising from this sympathetic tissue are termed extra-adrenal functional paraganglioma (eFPGL).
Parasympathetic paraganglia are located close to major arteries and nerves, e.g. carotid body, glomus jugulare, vagal, tympanic, pulmonary, and aorta. Tumours arising from the parasympathetic nervous system are referred to as head and neck paraganglioma (HNPGL), and only a minority of those shows endocrine activity (~25%).
Potential fatal hypertensive crises.
It is treatable hypertension
The lack of long-term efficacy of medical treatment and control
The appreciable incidence of malignancy.
The implications of the identification of an underlying genetic cause (>25% of cases, e.g. RET mutations and co-incident medullary carcinoma, VHL mutations and co-incident angiomas)
Algorithm for the tumor localization in patients with biochemically proven pheochromocytoma(PHEO). MIBG: 123I-metaiodobenzylguanidine; PET: positron emission tomography.*In patients with positive finding on CT/MRI imaging, MIBG scan may be considered in those withfamilial PHEO, young age (<20 yr), ectopic PHEO, and tumors larger than 5 cm in size.
Pheochromocytoma: CT scan of adrenalglands showing an 8 cm right adrenal mass, withcentral necrosis (arrow). The mass deforms thecontour of the liver without evidence ofinvasion.
123I-metaiodobenzylguanidine (MIBG) scanof patients with bilateralpheochromocytoma (A) andmetastatic pheochromocytoma (B). Arrows indicateabnormal uptake in the regionof adrenals in (A).
There is an association between peochromocytoma -ectodermal and the neuroectodermal diseases, most frequentlywith neurofibromatosis.
Monitor BP, pulse, and haematocrit. The goal is a BP of 130/80 or less sitting and 100mg systolic standing, pulse 60–70 sitting and 70–80 standing. Reversal of α-mediated vasoconstriction may lead to haemodilution (check Hb preoperatively).
To ensure complete blockade before surgery, IV phenoxybenzamine (1mg/kg over 4h in 100mL 5% glucose) can be administered on the 3 days before surgery. There is less experience with competitive α-adrenergic blockade, such as prazosin.
Phentolamine, nitroprusside, or IV nicardipine are useful to treat perioperative hypertension, and esmolol or propranolol for perioperative arrythmias.
Hypotension (e.g. after tumour devascularization) usually responds to volume replacement but occasionally requires inotropic support.