Pheochromocytoma

Harrisons Principles of Internal Medicine 18th ed., Chapter 343, pp. 2962-2967SK Biswas et al., A Case Report of Adrenal Pheochromocytoma, Faridpur Med. Coll. J. 2011;6(1):55-58

Learning ObjectivesTo identify pheochromocytoma and discuss its typical symptoms and presentation.

To discuss the management of hypertension related to pheochromocytoma.

Case Mrs. Afroza, 31 years old housewife admitted with the complaints of paroxysmal attacks of palpitation, diaphoresis, dizziness, blurring of vision and headache for the last 6 months. Each attack persists for few minutes to half an hour and occurs irregularly once within two to three days to 2 to 3 times a day. On examination, patient had no abnormal physical findings except Blood Pressure (BP) is high during paroxysmal attack (Systolic BP varies from 140 to 210 mmHg and diastolic BP varies from 100 to 140 mmHg). Complete Blood Count, Random Blood Sugar, Blood urea, Chest X-rays and ECG reports were within normal limit. CT (Computed Tomography) scan of abdomen shows right sided adrenal mass of a size about 6cm x 10 cm.

PRE-TESTKindly get sheet of paper

Question #1Enumerate the RULE OF TEN of pheochromocytoma?

1. 10% _______2. 10% _______3. 10% _______

Question #2Enumerate the CLASSICAL TRIAD of symptoms of pheochromocytoma?

Question #3What is the MOST dominant sign of pheochromocytoma?

Question #4What is the MOST sensitive biochemical test for the diagnosis of pheochromocytoma?

Question #5What is the ULTIMATE therapeutic goal for the treatment of pheochromocytoma?

Pheochromocytoma: IntroductionCatecholamine-producing tumors that can manifest a variety of symptoms which mimic other diseases.

EPIDEMIOLOGYOccurs in 2-8/million persons/year.0.1% of hypertensive patients Mean age of diagnosis at 40 yearsRULE OF TENS10% bilateral10% extra adrenal10% malignant

ETIOLOGYpheochromocytomareflects the black colored staining caused by chromaffin oxidation of catecholamines.Etiology is unknownparaganglioma- used to describe catecholamine-producing tumors in the head and neck.

CLINICAL FEATURESthe great masqueraderCLASSIC TRIAD of symptoms:PalpitationHeadacheProfuse sweatingHYPERTENSION- dominant sign

Clinical featurescontinuedCatecholamine crises Heart failure Pulmonary edemaArrhythmiasIntracranial hemorrhage

DIAGNOSISMeasurement of catecholaminesTraditionally the 1st step

Documentation of catecholamine excessBiochemical testingLocalization of the tumorDiagnostic imaging

DIAGNOSIS: Biochemical testingCatecholamines: Norepinephrine, epinephrine, dopamineIncreased in urine and plasma

Plasma metanephrineMost sensitive test

DIAGNOSTIC IMAGINGCT with contrastT2-weighted MRI with gadolinium contrast

TumorsMIBG111Insomatostatin analogues18F-dopa PET

Differential DiagnosisEssential hypertensionAnxiety attacksUse of cocaine or amphetaminesMastocytosisCarcinoid syndrome (usually lacking hypertension)Intracranial lesionsClonidine withdrawalAutonomic epilepsy Factitious crises (sympathomimetic amines)

Differentials continuedFor asymptomatic adrenal mass:Nonfunctioning adrenal adenomaAldosteronomaCortisol-producing adenoma (Cushings syndrome)

TREATMENTULTIMATE therapeutic goal: complete tumor removalPreoperative patient preparation:-adrenergic blockers (phenoxybenzamine) 5-10mg initially orally 3x/day for 7 days with typical final dose of 20-30mg 3x/day.

Oral prazosin or IV phentolamineFor paroxysmsBefore surgery- BP

Surgery:Nitroprusside infusionUseful for intraoperative hypertensive crisisAtraumatic endoscopic surgeryPost-op:Catecholamine normalization should be documented.ACTH to exclude cortisol deficiency

Malignant Pheochromocytoma5-10%Typical histologic criteria:Cellular atypiaPresence of mitoses Invasion of vessels or adjacent tissues

do not reliably identify which tumors have the capacity to metastasize

Malignant pheochromocytoma generally is restricted to tumors with distant metastases, most commonly found in lungs, bone, or liver, suggesting a vascular pathway of spread.

Treatmenttumor mass reductionalpha blockers for symptomsChemotherapydacarbazine (600 mg/m2 days 1 and 2)cyclophosphamide (750 mg/m2 day 1)vincristine (1.4 mg/m2 day 1), repeated every 21 days for three to six cycles.nuclear medicine radiotherapy.

Prognosisvariable, with a 5-year survival of 3060%.

Pheochromocytoma in Pregnancyoccasionally are diagnosed in pregnancyEndoscopic removal, 4th-6th month of gestationcan be followed by uneventful childbirth. Regular screening in families with inherited pheochromocytomas

Pheochromocytoma-Associated Syndromes2533% have inherited syndromemean age at diagnosis is about 15 years lower in patients with inherited syndromes compared with patients with sporadic tumors

Neurofibromatosis type 1 (NF 1)Classic features multiple neurofibromas, caf au lait spots, axillary freckling of the skin, and Lisch nodules of the iris Malignant pheochromocytoma is not uncommon

Cutaneous neurofibromas

Lisch nodules of the iris

axillary freckling of the skin

Multiple Endocrine Neoplasia (MEN 2A, MEN 2B) MEN 2A characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism; MEN 2B includes MTC and pheochromocytoma, as well as multiple mucosal neuromas, marfanoid habitus, and other developmental disorders, though it typically lacks hyperparathyroidism. MTC is seen in virtually all patients with MEN 2, but pheochromocytoma occurs in only about 50% of these patients. Nearly all pheochromocytomas are benign and located in the adrenals, often bilateral

Von Hippel-Lindau syndrome (VHL) autosomal dominant disorder predisposes to retinal and cerebellar hemangioblastomas, which also occur in the brainstem and spinal cord Features:clear cell renal carcinomas, pancreatic islet cell tumors, endolymphatic sac tumors (ELSTs) of the inner ear, cystadenomas of the epididymis and broad ligament, and multiple pancreatic or renal cysts.

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POST-TESTPlease write your answers at the back of Pre-Test