Case #5

Ephraim R. CaangayPharmacology BFebruary 7, 2007

The Case

• GP, 23 year old female, sought consultation at Fatima Medical Center due to intermittent attacks of severe headaches, palpitations and sweating.

• PE revealed an elevated BP = 180/100 and tachycardia (CR = 100/min).

• Attending physician requested for a 24 hour urine VMA determination which revealed an elevated result = 15 mg/24 hours.

Initial Differential Diagnosis

• Cocaine Abuse• Migraine – pain in the head (usually

unilateral), vertigo, nausea and vomiting, photophobia, and scintillating appearances of light.

• Possible CVA – “intermittent attacks” wrong presentation

• Brain Tumor – “intermittent attacks” wrong presentation

• Angina Pectoris• Anxiety Disorders• Hyperthyroidism

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The Case (cont’)

• Attending physician requested for a 24 hour urine VMA determination which revealed an elevated result = 15 mg/24 hours.

VMA?

• VMA – Vanillyl Mandelic Acid

• The major urinary metabolite of adrenal and sympathetic catecholamines; elevated in most patients with pheochromocytoma.

Pheochromocytoma• Considered an endocrinologic secondary cause of

hypertension • A functional chromaffinoma, usually benign, derived

from adrenal medullary tissue cells and characterized by the secretion of catecholamines, resulting in hypertension

• Hypertension may be paroxysmal and associated with attacks of palpitation, headache, nausea, dyspnea, anxiety, pallor, and profuse sweating.

• Pheochromocytomas are not innervated, and catecholamine release is not precipitated by neural stimulation

Incidence

• Race – can occur in any race

• Gender – occurs equally in males and females

• Age – can occur at any age, with peak between 30 – 50.

Biological Effects Of Catecholamines

• Stimulation of alpha-adrenergic receptors – elevated blood pressure– increased cardiac contractility– glycogenolysis– Gluconeogenesis– intestinal relaxation

• Stimulation of beta-adrenergic receptors – increase in heart rate – Increase in contractility.

Typical Clinical History

Spells characterized by: • Headaches• Palpitations• diaphoresis All in association with severe hypertension

(possibly paroxysmal). • Typical progressively worsen, increase in

frequencyWithout these symptoms and hypertension, can

rule out pheochromocytoma diagnosis.

Other Clinical Signs

• Hypertension (paroxysmal in 50% of cases)

• Postural hypotension: Hypertensive retinopathy

• Weight loss • Pallor

• Fever • Tremor • Neurofibromas Café

au lait spots• Tachyarrhythmias • Pulmonary edema • Cardiomyopathy • Ileus

Lab Diagnosis• Perform a 24-hour urine collection for creatinine,

total catecholamines, vanillyl mandelic acid, and metanephrines. – Measure creatinine in all collections of urine to

ensure adequacy of the collection. – Metanephrine levels are considered the most

sensitive and specific test for a pheochromocytoma, while vanillylmandelic acid is the least specific test and has a false-positive rate greater than 15%.

– The collection container should be dark and acidified and should be kept cold to avoid degradation of the catecholamines.

Imaging Studies

• Perform imaging studies after lab diagnosis of a pheochromocytoma.

• MRI is preferred over CT scanning. – sensitivity of up to 100% in detecting adrenal

pheochromocytomas, – does not require contrast, – does not expose the patient to ionizing radiation. – MRI is also superior to CT scanning for detecting extra-adrenal

pheochromocytomas.

• CT – an accuracy of 85-95% for detecting adrenal masses with a

spatial resolution of 1 cm or greater. – less accurate for lesions smaller than 1 cm.

Histologic Findings

• Pheochromocytomas vary from 2 g to 3 kg but, on average, weigh 100 g (normal: 4-6 g).

• These tumors are well encapsulated, highly vascular, and appear reddish brown on cut section.

• the tumor cells are arranged in balls and clusters separated by endothelial-lined spaces: zellballen.

• The cells vary in size and shape and have finely granular basophilic or eosinophilic cytoplasm.

• The nuclei are round or oval with prominent nucleoli. • Nuclear giantism and hyperchromasia are common.

Treatment• Surgical resection, but first need to medically stabilize.

– Preferable to remove only affected adrenal gland– If both are removed, patient requires lifetime glucocorticoid

and mineralocorticoid replacement therapy

• Use non-selective alpha-adrenergic antagonists to control hypertension– DOC: phenoxybenzamine– Phentolamine

• If significant tachycardia is experienced after alpha blockade, give non-selective beta-adrenergic blockers– DOC: Propranolol

Prognosis

• Because of excessive catecholamine secretion precipitate life-threatening hypertension or cardiac arrhythmias.

• If Dx of is overlooked, the consequences could be disastrous, even fatal

• However, if a pheochromocytoma is found, it is potentially curable