Seminar on phaeochromocytoma.

1. By Sanjay George
PHAEOCHROMOCYTOMA

2. INTRODUCTION
• Phaeochromocytomas and paragangliomas are
catecholamine producing tumors derived from
sympathetic or parasymapathetic nervous
system.
• Can be sporadic or inherited.

3. EPIDEMIOLOGY
• Seen in 2-8 out of 1 million persons per year.
• 0.1% of hypertensive patients harbor a
phaeochromocytoma.
• Rule of ten : 10% bilateral
• 10% extra adrenal
• 10% malignant
• 10% not associated with hypertension
• 10% in children

4. ETIOLOGY AND PATHOGENESIS
• Both are well vascularized tumors that arise from
sympathetic(eg: Adrenal medulla) or
parasympathetic(eg: Carotid Body, Glomus Vagale)
paraganglia.
• Phaeochromocytoma – catecholamine producing
tumors including those in extra adrenal
retroperitoneal, pelvic and thoracic sites.
• Paraganglioma – catecholamine producing tumors in
the head and neck as well as tumors arising from
parasympathetic system, which may secrete little or
no catecholamine.

5. • Etiology of sporadic cases unknown.
• 25% of patients have inherited condition
including germ line mutations in
RET, VHL, NF1, SDHB, SDHC, SDHD genes.

7. PATHOLOGY

8. CLINICAL FEATURES
• The ‘Great Masquerader’.
• Episodes of headache, palpitation and profuse
sweating constitute a classic triad.
• Presence of all 3 symptoms along with
hypertension makes phaeochromocytoma a likely
diagnosis.
• Dominant sign is hypertension which is classically
episodic.

9. • Catecholamine crises can lead to heart
failure, pulmonary edema, arrythmias and
intracranial hemorrhage.
• During episode of hormone release patients are
pale anxious and experience tachycardia and
palpitations. These episodes usually last for an hour
and can be precipitated by surgery, positional
changes, exercise, pregnancy, urination, and various
medications.
• Phaeochromocytomas can also be asymptomatic for
many years.

10. • Headaches
• Sweating attacks
• Palpitation and tachycardia
• Hypertension, sustained or
paroxysmal
• Anxiety and panic attacks
• Pallor
• Nausea
• Abdominal Pain
• Weakness
• Weight loss
• Paradoxical response to
antihypertensive drugs
• Polyuria and Polydipsia
• Constipation
• Orthostatic hypotension
• Dilated cardiomyopathy
• Erythrocytosis
• Elevated Blood Sugar
• Hypercalcemia

11. • Diagnostic Method:
- 24 hour urinary tests
Vanillylmandelic acid
Catecholamines
Fractioned metanephrines
Total metanephrines
- Plasma Tests
Catecholamines
Free Metanephrines
Chromogranin A
• CT
• MRI
• MIBG Scintigraphy
• Somatostatin receptor
scintigraphy
• Dopa PET
DIAGNOSIS

12. TREATMENT
• Complete tumor removal is the ultimate therapeutic
goal.
• Pre-operative preparation using alpha blockers
should be initiated. – Phenoxybenzamine
• Adequate alpha blockade requires 10 – 14 days
• Oral prazosin or IV phentolamine can be used to
manage paroxysms.
• Beta blockers can be added if tachycardia persists.

13. • Blood pressure can be labile during
surgery, particularly at onset of intubation and
when manipulating tumor.
• Nitroprusside infusion is useful for intraoperative
hypertensive crises.

14. MALIGNANT
PHAEOCHROMOCYTOMA
• Around 10% are malignant.
• Diagnosis is difficult.
• Refers to tumors with distant metastases to
lung, bone, liver suggesting vascular spread.
• More common in hereditary cases.
• Treatment:
Chemotherapy: Dacarabazine + cyclophosphamide
+vincristin
Radiotherapy
Prognosis : 5 year survival rate of 30 – 60%

15. PHAEOCHORMOCYTOMA IN
PREGNANCY
• Phaeochromocytomas are occasionally diagnosed
in pregnancy.
• Endoscopic removal preferably in fourth to sixth
month of gestation is possible and can be
followed by uneventful childbirth.

16. PHAEOCHROMOCYTOMA
ASSOCIATED SYNDROMES
• 25 – 33% of patients with phaeochromocytoma
have an inherited syndrome.
• Neurofibromatosis type 1 – changes in NF1 gene
Phaeochromocytoma occurs in 1% of these
patients.
• Classical features include multiple
neurofibromas, café au lait spots, axillary
freckling of skin and Lisch nodules of the iris.

17. • Multiple Endocrine Neoplasia type 2A and 2B
• Autosomal dominant disorder
• Both types caused by mutations in RET gene.
• MEN 2A : Medullary thyroid
carcinoma, phaeochromocytoma and
hyperparathyroidism.
• MEN 2B : Medullary thyroid
carcinoma, phaeochromocytoma and multiple
mucosal neuromas
• Phaeochromocytoma seen in 50% of patients of
MEN2.

18. • Von Hippel-Lindau syndrome
• Autosomal dominant disorder that predisposes to
retinal and cerebellar hemangioblastomas. Also
predisposes to renal clear carcinoma, pancreatic
islet cell tumours, endolympatic sac tumors of the
inner ear etc,.
• Associated with mutations of VHL gene.
• 20 – 30% of patients with VHL syndrome have
pheochromocytoma.

19. PARAGANGLIOMA SYNDROMES
• Associated with mutations in SDH genes:
SDHB(PGL4), SDHC(PGL3), SDHD(PGL1)
• Transmission is autosomal dominant.