Pheochromocytoma (PCA) By Dr. Usama Ragab Youssif Lecturer of Medicine Zagazig University Pheochromocytoma and paraganglioma

1. Suprarenal Medulla
Usama Ragab Youssif, MD
Lecturer of Medicine
Zagazig University
Email: usamaragab@medicine.zu.edu.eg
Slideshare: https://www.slideshare.net/dr4spring/
Mobile: 00201000035863

2. Suprarenal
Gland

3. Medulla
It is sympathetic ganglia which secretes CA.

4. Nomenclature

5. Pheochromocytoma
and Ganglioma
Phaeochromocytomas (aPCA) are
chromaffin tumors arising from the
adrenal medulla and secreting CA.
90% benign, 90% adrenal, 90%
unilateral (bilateral in familial
syndromes).
Paragangliomas (PGL) are tumours
arising from extra-adrenal sympathetic
or parasympathetic nervous tissue.

6. Pheochromocytoma
and Ganglioma (cont.)
• Sympathetic paraganglia occur as follows: in
prevertebral, paravertebral, thoracoabdominal,
etc. They are termed extra-adrenal functional
paraganglioma (eFPGL).
• 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%).

7. Notes
The cells in the adrenal medulla produce
epinephrine and norepinephrine but the
extra adrenal chromaffin cells make only
norepinephrine.
PCA is found in 0.1% of patients with severe
hypertension and in less than 0.05% of all
hypertensive patients.
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
of PCA
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.

9. Epidemiology
Equal sex
incidence
3rd and 4th
decade

10. Secretory
products
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
concentrations.
Pure dopamine secretion is rare and may be associated with hypotension.
These tumours are more likely to be malignant.

11. Importance
of diagnosis
Fatal Crises
Treatable
Need Intervention
Malignancy?
Underlying genetic cause (>25% of cases)

12. Presentation
The presence of palpitation, headaches, or sweating
in a patient with hypertension should raise the
diagnostic query of PCA.
• General:
Sweating and heat intolerance >80%.
Pallor or flushing.
Feeling of apprehension.
Pyrexia

13. Presentation
(cont.)
Hypertension: Sustained or episodic
hypertension often resistant to conventional
therapy
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

14. Presentation
(cont.)
Cardiovascular and vasomotor: palpitations (65%),
chest pain, dyspnea, postural hypotension, flushing.
GI: abdominal pain, constipation?, nausea.
Skin: livedo reticularis.
Endocrine: paroxysmal thyroid swelling
(noradrenaline-secreting).
Others: weight loss, polyuria, nocturia

15. Why sometimes there is hypotension
Dehydration Release of adrenomedulline

16. Complications
1. CVS: LVF, DCM (reversible), hypertension,
arrhythmia
2. Pulmonary: pulmonary edema
3. Metabolic: impaired glucose tolerance,
hypercalcemia
4. CNS: hypertensive encephalopathy, target
organ damage

17. Factors that may precipitate crisis
1. Straining
2. Exercise
3. Abdominal palpation
4. Surgery
5. Drugs e.g., beta blockers, IV contrast,
anesthesia, tricyclic antidepressant,
metocloperamide, glucagon

18. Take Care
Differential diagnosis
• Anxiety-panic attacks
• Hypoglycemia
• Other causes of hypertension =
2ry hypertension
• Diencephalic or autonomic
epilepsy (attacks of hypertension
with increased CA
Endocrine causes of excess sweating
• Thyrotoxicosis
• Acromegaly
• Hypoglycemia
• Pheochromocytoma

19. Workup

20. Who should
be screened?
1. Patients with a family history of MEN, VHL,
NF1.
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.

21. Two Questions
What is the lesion = screen
Where is the lesion = localize

22. What is the lesion

23. 1- 24h urine collection for
catecholamines/metanephrines
• 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

26. Comparable tests
Test Sensitivity % Specificity %
Plasma metanephrines 97 92
Urinary metanephrines 85 95
Urinary catecholamines 88 78
Urinary VMA 65 88
Clonidine suppression test 97
MRI 98 70
CT 93 70
MIBG 80 95

27. List of medications
and stimulants to
avoid before the
measurement of
plasma and urinary
catecholamines and
metanephrines
• Tricyclic antidepressants
• Beta-blockers: labetalol* and sotalol
• Acetaminophen
• Phenoxybenzamine
• Monoamine oxidase inhibitors
• Antipsychotics
• Sympathomimetics: ephedrine, pseudoephedrine,
amphetamines, albuterol
• Stimulants: caffeine, nicotine, theophylline
• Miscellaneous: levodopa, carbidopa, alcohol, cocaine
*Labetalol interferes only with certain assays

28. Where is the lesion

29. Localization
It is easily localized (large) in
contrast to Conn’s syndrome
MRI: Bright hyperintense image on
T2.
CT: Less sensitive and specific—less
good at distinguishing between
different types of adrenal tumours.

30. Localization
(cont.)
Metaiodo-benzylguanidine (MIBG) produces
specific uptake in sites of sympathetic activity:
Specificity is nearly 100%, localization of extra-
adrenal tumors, performed preoperatively.
PET scan: [18F]fluorodeoxyglucose (FDG) and
the norepinephrine analogue
[11C]metahydroxyephedrine (mHED) have both
been used as radionucleotides.

31. Algorithm for the tumor localization in patients
with biochemically proven pheochromocytoma

32. CT and MRI

33. MIBG

34. What about genetic
condition? When to
screen?
1. Bilateral tumours.
2. Extra-adrenal tumour, including head and neck.
3. Age of onset (<50 years 45%).
4. Malignancy.
MEN II VHL NF1
Serum calcium.
Serum calcitonin
(phaeochromocytomas
precede medullary thyroid
carcinoma in 10%).
Ophthalmoscopy—retinal
angiomas are usually the
first manifestation.
MRI—posterior fossa and
spinal cord.
US of kidneys—if not
adequately imaged on MRI
of adrenals.
Clinical examination for
café-au-lait spots and
cutaneous neuromas.

37. Treatment

38. 1- Medical
α-blockade must be commenced before B-blockade to avoid
precipitating a hypertensive crisis due to unopposed
stimulation
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.

40. Metyrosine
• 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
benign.

42. Risk factors for haemodynamic instability
during surgery include
High noradrenaline concentration
Large tumour size
Postural drop after B-blockade, and a MAP >100mmHg

44. Follow-up
Clinical & biochemical follow up after surgery.
Cure is assessed by 24h urinary free
catecholamine measurement after 2 weeks
post-operatively.
CA levels should be checked annually
Chromogranin A is also a useful marker

45. Thank you