By Sanjay George

PHAEOCHROMOCYTOMA

INTRODUCTION• Phaeochromocytomas and paragangliomas are

catecholamine producing tumors derived from sympathetic or parasymapathetic nervous system.

• Can be sporadic or inherited.

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

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.

• Etiology of sporadic cases unknown.

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

PATHOLOGY

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.

• 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.

• 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

• 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

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.

• Blood pressure can be labile during surgery, particularly at onset of intubation and when manipulating tumor.

• Nitroprusside infusion is useful for intraoperative hypertensive crises.

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%

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.

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.

• 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.

• 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.

PARAGANGLIOMA SYNDROMES

• Associated with mutations in SDH genes: SDHB(PGL4), SDHC(PGL3), SDHD(PGL1)

• Transmission is autosomal dominant.

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