INTRODUCTION• Phaeochromocytomas and paragangliomas arecatecholamine producing tumors derived fromsympathetic or parasymapathetic nervoussystem.• Can be sporadic or inherited.
EPIDEMIOLOGY• Seen in 2-8 out of 1 million persons per year.• 0.1% of hypertensive patients harbor aphaeochromocytoma.• 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 fromsympathetic(eg: Adrenal medulla) orparasympathetic(eg: Carotid Body, Glomus Vagale)paraganglia.• Phaeochromocytoma – catecholamine producingtumors including those in extra adrenalretroperitoneal, pelvic and thoracic sites.• Paraganglioma – catecholamine producing tumors inthe head and neck as well as tumors arising fromparasympathetic system, which may secrete little orno catecholamine.
• Etiology of sporadic cases unknown.• 25% of patients have inherited conditionincluding germ line mutations inRET, VHL, NF1, SDHB, SDHC, SDHD genes.
CLINICAL FEATURES• The ‘Great Masquerader’.• Episodes of headache, palpitation and profusesweating constitute a classic triad.• Presence of all 3 symptoms along withhypertension makes phaeochromocytoma a likelydiagnosis.• Dominant sign is hypertension which is classicallyepisodic.
• Catecholamine crises can lead to heartfailure, pulmonary edema, arrythmias andintracranial hemorrhage.• During episode of hormone release patients arepale anxious and experience tachycardia andpalpitations. These episodes usually last for an hourand can be precipitated by surgery, positionalchanges, exercise, pregnancy, urination, and variousmedications.• Phaeochromocytomas can also be asymptomatic formany years.
TREATMENT• Complete tumor removal is the ultimate therapeuticgoal.• Pre-operative preparation using alpha blockersshould be initiated. – Phenoxybenzamine• Adequate alpha blockade requires 10 – 14 days• Oral prazosin or IV phentolamine can be used tomanage paroxysms.• Beta blockers can be added if tachycardia persists.
• Blood pressure can be labile duringsurgery, particularly at onset of intubation andwhen manipulating tumor.• Nitroprusside infusion is useful for intraoperativehypertensive crises.
MALIGNANTPHAEOCHROMOCYTOMA• Around 10% are malignant.• Diagnosis is difficult.• Refers to tumors with distant metastases tolung, bone, liver suggesting vascular spread.• More common in hereditary cases.• Treatment:Chemotherapy: Dacarabazine + cyclophosphamide+vincristinRadiotherapyPrognosis : 5 year survival rate of 30 – 60%
PHAEOCHORMOCYTOMA INPREGNANCY• Phaeochromocytomas are occasionally diagnosedin pregnancy.• Endoscopic removal preferably in fourth to sixthmonth of gestation is possible and can befollowed by uneventful childbirth.
PHAEOCHROMOCYTOMAASSOCIATED SYNDROMES• 25 – 33% of patients with phaeochromocytomahave an inherited syndrome.• Neurofibromatosis type 1 – changes in NF1 genePhaeochromocytoma occurs in 1% of thesepatients.• Classical features include multipleneurofibromas, café au lait spots, axillaryfreckling 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 thyroidcarcinoma, phaeochromocytoma andhyperparathyroidism.• MEN 2B : Medullary thyroidcarcinoma, phaeochromocytoma and multiplemucosal neuromas• Phaeochromocytoma seen in 50% of patients ofMEN2.
• Von Hippel-Lindau syndrome• Autosomal dominant disorder that predisposes toretinal and cerebellar hemangioblastomas. Alsopredisposes to renal clear carcinoma, pancreaticislet cell tumours, endolympatic sac tumors of theinner ear etc,.• Associated with mutations of VHL gene.• 20 – 30% of patients with VHL syndrome havepheochromocytoma.
PARAGANGLIOMA SYNDROMES• Associated with mutations in SDH genes:SDHB(PGL4), SDHC(PGL3), SDHD(PGL1)• Transmission is autosomal dominant.